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Item Integrating mental health into primary health care: local initiatives from Uganda(World Psychiatry, 2007) Ovuga, Emilio; Boardman, Jed; Wasserman, DanutaUganda has passed through political and bloody civil strife stretching over 40 years. Since 1987 the HIV/AIDS pandemic has compounded the problems of the country. The present paper describes some initiatives to develop mental health services in one district of the country. A bottom-up approach in the district resulted in the formation of a community-led mental health program with strong support from two self-help groups, district political leaders and district representatives in parliament. Primary health care providers at all levels of health care in the district were trained in order to make services accessible to the rural population. Further plans based on initial exploratory discussions aim to involve the education department, the welfare and probation office, prisons and police, the military, church and cultural leaders and traditional healers. These initiatives show that it is possible to empower communities to participate in the development of mental health programs in a low-income country.Item Improving the Availability and Management of Essential AIDS and TB Medicines and Diagnostics in Uganda(HEPS-Uganda, 2008) HEPS-UgandaA free ARV programme implemented with support from external donors has over the past few years led to a significant increase in the number of people living with HIV/AIDS (PHAs) accessing antiretroviral therapy (ART). By 2006/7, about 105,000 PHAs were receiving ART from 313 centres. Given the relatively wide range of ARVs available for prescription to PHAs, Uganda is well into the modern trends of AIDS treatment. The substantial availability of combination ARVs brings with it the advantages of a reduced pill burden and thus, improved adherence. In addition, the availability levels of medicines at treatment centres located in rural areas is comparable to those in urban locations, suggesting the medicine distribution system is generally fair. These advances in the treatment effort however, mask the reality, extent and impact of stock-outs of the essential AIDS ad TB medicines in the accredited centres. Access to affordable medicines is a human right enshrined in the UN Universal Declaration on Human Rights, which together with subsequent UN statements, affirms people’s right to health. The reliable provision of ART to at least the people who are registered to receive it is therefore a key component of an adequate, functioning health care system that enables people to realise their right to health. As government plans to roll out ART to 80% of Health Centre IV’s by 2010, it is important to consider whether the present PHAs on ART can access treatment at the accredited health facilities. Besides risking their lives, if treatment of PHAs is interrupted for one reason or another, they are likely to develop resistance to the medicines they are currently taking, which could lead to emergence of resistant strains of HIV among the general society if any of the affected PHAs transmits HIV to other people.Item Global Fund: Making Uganda’s CCM Work Through Full Engagement of Civil Society(HEPS, 2008) HEPSHIV/AIDS have over the recent years been receiving increasing funding, especially from the donor community. However, due to the absence of a mechanism to monitor and aggregate the contributions from the wide range of funders, the exact amount of funding coming from foreign donors, non-governmental organisations, individuals and even the Uganda government itself, is not known. Independent attempts to determine the actual level of funding have been hampered by the Ministry of Health’s failure to harmonize the various funding structures of the different funders, the multi-sectoral nature of the response, reluctance by the donors to provide complete information about their budgets and expenditure, and difficulty in capturing household contributions towards HIV/AIDS care. There is therefore, a gap that needs to be filled by regular tracking of HIV/AIDS funding, to establish the actual level of funding and the extent to which it reaches the intended beneficiaries. Even with the limited information available, it is obvious that funding for HIV/AIDS is still insufficient, given that access to HIV/AIDS services – from counseling and testing (HCT) to anti-retroviral therapy (ART) and care and support – remains limited. The health care system is urgently in need of additional resources, particularly to accommodate the burden of the HIV/AIDS epidemic. The public sector needs not only to increase its per capita health expenditure to US$28 – and up to US$40 when anti-retroviral drugs (ARVs) are included – to enable its citizens realise their right to health, but also to make the available work for the poor.Item Ill-health and labour market outcomes in Uganda(The African Economic Research Consortium, 2009) Matovu, Fred; Birungi, Patrick; Sebaggala, RichardThe role health plays in reducing poverty and economic development particularly in developing countries is undisputable in the economic literature (Audibert, 2009) Health of the population is a key factor for labor productivity, poverty reduction and overall economic development. Healthier workers are physically and mentally more energetic and robust; productive and tend to earn higher wages; and they are also less likely to be absent from work because of illness (or illness in their family) (Bloom et al, 2004). Most recently, the links between population health and economic productivity have become a significant policy concern (Tompa, 2002). In Uganda, although the national health indicators look good, ill health is a growing problem in both rural and urban areas, particularly among the poor. The improvement health indicators have been largely brought about by efficiency gains rather than big increases in overall health sector resource envelope. Therefore, there is feeling among policy makers and researchers that if spending in the health sector is increased, the 75% preventable disease burden can be reduced enormously.Item Community involvement in MDP 301 microbicide trial in Masaka: Successes and failures(HEPS-Uganda Policy Briefing Series, 2010) HEPSThe MDP 301 microbicide trial used multiple approaches at the Masaka site to mobilise and sensitise the community, get feedback, share information, and communicate the final trial results. While this broad approach contributed to the success of the trial, a survey conducted early 2010 found no evidence that civil society advocacy groups were invited to contribute to the trial’s design and implementation. By outlining the key successes and failures of the trial’s community involvement initiatives, this brief highlights the need for HIV prevention research in general to follow good community participatory practice guidelines by nurturing local advocates from the civil society to partner with the investigators in the conduct of research.Item Mycobacterium tuberculosis Microbiologic and Clinical Treatment Outcomes in a Randomized Trial of Immediate versus CD4+ -Initiated Antiretroviral Therapy in HIV-Infected Adults with a High CD4+ Cell Count(Clinical infectious diseases, 2010) Chamie, Gabriel; Charlebois, Edwin D.; Walusimbi-Nanteza, Maria; Mugerwa, Roy D.; Mayanja, Harriet; Okwera, Alphonse; Whalen, Christopher C.; Havlir, Diane V.In a prospective randomized, controlled trial in Uganda comparing the efficacy of antiretroviral therapy during tuberculosis therapy with the efficacy of tuberculosis therapy alone in HIV-infected patients with tuberculosis who have a CD4+ cell count >350 cells/µL, it was found that antiretroviral therapy did not accelerate microbiologic, radiographic, or clinical responses to tuberculosis therapy: 18% of participants had sputum smears positive for Mycobacterium tuberculosis after 5 months of tuberculosis therapy, despite having had negative culture results.Item Fertility in African communities affected by HIV(MRC/UVRI Research Unit on AIDS., 2011) Lutalo, Tom; Ssempijja, VictorUganda is famous for its success in bringing down HIV levels, but has persistently high fertility: on average women have seven children by the time they finish childbearing. The resulting high rates of population growth are detrimental to development and will make it difficult for high quality health and education services to keep up with the growing population.Item Effect of the Transposable Element Environment of Human Genes on Gene Length and Expression(Genome biology and evolution, 2011) Jjingo, Daudi; Huda, Ahsan; Gundapuneni, Madhumati; Leonardo Mari o-Ramırez, Leonardo Marin˜ o-Ramı´rez3,4, and I. King Jordan; Jordan, I. KingIndependent lines of investigation have documented effects of both transposable elements (TEs) and gene length (GL) on gene expression. However, TE gene fractions are highly correlated with GL, suggesting that they cannot be considered independently. We evaluated the TE environment of human genes and GL jointly in an attempt to tease apart their relative effects. TE gene fractions and GL were compared with the overall level of gene expression and the breadth of expression across tissues. GL is strongly correlated with overall expression level but weakly correlated with the breadth of expression, confirming the selection hypothesis that attributes the compactness of highly expressed genes to selection for economy of transcription. However, TE gene fractions overall, and for the L1 family in particular, show stronger anticorrelations with expression level than GL, indicating that GL may not be the most important target of selection for transcriptional economy. These results suggest a specific mechanism, removal of TEs, by which highly expressed genes are selectively tuned for efficiency. MIR elements are the only family of TEs with gene fractions that show a positive correlation with tissue-specific expression, suggesting that they may provide regulatory sequences that help to control human gene expression. Consistent with this notion, MIR fractions are relatively enriched close to transcription start sites and associated with coexpression in specific sets of related tissues. Our results confirm the overall relevance of the TE environment to gene expression and point to distinct mechanisms by which different TE families may contribute to gene regulation.Item Prediction of Transposable Element Derived Enhancers Using Chromatin Modification Profiles(PLoS ONE, 2011) Huda, Ahsan; Tyagi, Eishita; Marino-Ramırez, Leonardo; Bowen, Nathan J.; Jjingo, Daudi; Jordan, I. KingExperimentally characterized enhancer regions have previously been shown to display specific patterns of enrichment for several different histone modifications. We modelled these enhancer chromatin profiles in the human genome and used them to guide the search for novel enhancers derived from transposable element (TE) sequences. To do this, a computational approach was taken to analyze the genome-wide histone modification landscape characterized by the ENCODE project in two human hematopoietic cell types, GM12878 and K562. We predicted the locations of 2,107 and 1,448 TE-derived enhancers in the GM12878 and K562 cell lines respectively. A vast majority of these putative enhancers are unique to each cell line; only 3.5% of the TE-derived enhancers are shared between the two. We evaluated the functional effect of TE-derived enhancers by associating them with the cell-type specific expression of nearby genes, and found that the number of TE-derived enhancers is strongly positively correlated with the expression of nearby genes in each cell line. Furthermore, genes that are differentially expressed between the two cell lines also possess a divergent number of TE derived enhancers in their vicinity. As such, genes that are up-regulated in the GM12878 cell line and down-regulated in K562 have significantly more TE-derived enhancers in their vicinity in the GM12878 cell line and vice versa. These data indicate that human TE-derived sequences are likely to be involved in regulating cell-type specific gene expression on a broad scale and suggest that the enhancer activity of TE-derived sequences is mediated by epigenetic regulatory mechanisms.Item Reducing the Burden of Diarrhoea among Urban Households in Uganda(Economic Policy Research Centre, 2012) Barungi, Mildred; Kasirye, IbrahimDiarrhoea remains a big challenge to attainment of water related Millennium Development Goals (MDGs) in Uganda. This brief examines the cost effectiveness of two water technologies in preventing Diarrhoea illness among urban households in Uganda. We estimate the reduction in the burden of disease arising from accessing either public stand-pipes or boreholes in urban areas. DetailsItem On the presence and role of human gene-body DNA methylation(Oncotarget, 2012) Jjingo, Daudi; Conley, Andrew B.; Yi, Soojin V.; Lunyak, Victoria V.; Jordan, I. KingDNA methylation of promoter sequences is a repressive epigenetic mark that down-regulates gene expression. However, DNA methylation is more prevalent within gene-bodies than seen for promoters, and gene-body methylation has been observed to be positively correlated with gene expression levels. This paradox remains unexplained, and accordingly the role of DNA methylation in gene-bodies is poorly understood. We addressed the presence and role of human gene-body DNA methylation using a meta-analysis of human genome-wide methylation, expression and chromatin data sets. Methylation is associated with transcribed regions as genic sequences have higher levels of methylation than intergenic or promoter sequences. We also find that the relationship between gene-body DNA methylation and expression levels is non-monotonic and bell-shaped. Mid-level expressed genes have the highest levels of gene-body methylation, whereas the most lowly and highly expressed sets of genes both have low levels of methylation. While gene-body methylation can be seen to efficiently repress the initiation of intragenic transcription, the vast majority of methylated sites within genes are not associated with intragenic promoters. In fact, highly expressed genes initiate the most intragenic transcription, which is inconsistent with the previously held notion that gene-body methylation serves to repress spurious intragenic transcription to allow for efficient transcriptional elongation. These observations lead us to propose a model to explain the presence of human gene-body methylation. This model holds that the repression of intragenic transcription by gene-body methylation is largely epiphenomenal, and suggests that gene-body methylation levels are predominantly shaped via the accessibility of the DNA to methylating enzyme complexes.Item Building Effective Drinking Water Management Policies In Rural Africa: Lessons From Northern Uganda(CIGI-Africa Initiative, 2012) Opio, ChristopherThe importance of providing clean, safe drinking water and sanitation to rural inhabitants of developing countries is widely recognized. The United Nations (UN) General Assembly, for instance, declared 2008 the International Year of Sanitation, and the World Bank has been increasing financial assistance to developing countries in support of water supply and sanitation improvements (Cho, Ogwang and Opio, 2010). Despite the Millennium Development Goal (MDG) to reduce, by half, the number of people without sustainable access to clean and safe drinking water and basic sanitation by 2015 (Cho, Ogwang and Opio, 2010; Opio, 2010), most countries in Sub-Saharan Africa are not on track to meet the widely adopted deadline (Harvey, 2007; United Nations Children’s Fund [UNICEF], 2012; Abenaitwe, 2012).Item Addressing the Poor Nutrition of Ugandan Children(Economic Policy Research Centre (EPRC), 2012) Ssewanyana, Sarah; Kasirye, IbrahimOne out of every three young children in Uganda are short for their age, according to the 2011 Uganda Demographic and Health Survey (UDHS); and the incidence of poor nutritional status is highest in the relatively better off sub region of South Western Uganda. Although poor child nutrition status is a pervasive global problem, it is mainly concentrated in a few developing countries. According to the United Nations Children’s Fund (UNICEF) 24 developing countries account for over 80 percent of the world’s 195 million children faced with stunting. Out of the 24 countries, at least 11 are from Sub Saharan Africa (SSA). Furthermore, countries in SSA have made the least progress in reducing stunting rates—from 38% to 34% between 1990 and 2008—compared to a reduction of 40% to 29% for all developing countries. Uganda is among the developing countries with the largest population of stunted children—an estimated 2.4 million children aged less than 5 years in Uganda are stunted and this places the country at the rank of 14th—based on the ranking of countries with large populations of nutritionally challenged childrenItem Better nutrition for children in Uganda The policy makers role(Economic Policy Research Centre (EPRC), 2012) Kasirye, IbrahimUganda has made tremendous progress in improving welfare outcomes in the past 20 years, some key welfare outcomes especially regarding nutritional status have performed dismally. For instance, the proportion of poor persons reduced from 56% in 1992 to 25% by 2010. Also, the infant mortality rate (IMR) reduced from 81 to 54 death per 1000 live birth during 1995-2011. Similarly, the HIV/AIDS prevalence rate reduced from 30% in the early 1990s to 6.7% by 2011. On the other hand, Uganda continues to maintain a large population of malnourished children and women and this dents the country’s impressive human development record. According to population based data from Uganda Demographic and health Surveys (UDHS) of 2006 and 2011, 2,314,620 children under the age of five are too short for their age (stunted). An estimated 250,000 children under the age of five suffer from severe acute malnutrition annually and are in need of medical treatment. However, the most recent estimates from the 2011 UDHS indicate that child stunting rates have declined in the past five years. The proportion of children aged below 5 years classified as stunted declined from 38% in 2006 to 33% by 2011 (Figure 1). Furthermore Figure 1 shows that Uganda has registered mixed progress regarding child nutritional health indicators and the country may not meet the Millennium Development Goal (MDG) 1 target of halving Uganda’s underweight levels from 25% in 1990 to 12% by 2015. Worse still, Uganda appears to off the mark with regard to the target of halving the population below the minimum level of dietary energy consumption— the level of food insecurity has remained above the 60% mark since the 1990s.Item Cost Effectiveness of Reproductive Health Interventions in Uganda: The Case for Family Planning services(The African Economic Research Consortium, 2013) Ssewanyana, Sarah; Kasirye, IbrahimThere seems to be a consensus among policymakers and politicians that innovative interventions have to be put in place to reduce the population growth rates in Uganda. The country’s population growth rate of 3.2% per annum is extremely high — even for a low income country. The above scenario is attributed to high number births per woman as measured by the Total Fertility Rate (TFR) and this has remained substantially above levels elsewhere in sub‐Saharan Africa (SSA). For example, in 2006 Uganda’s TFR of 6.7 births per woman was higher than the SSA average of 5.5 births per woman. On the other hand, with an annual per capita Gross Domestic Product (GDP) of US$ 300, Uganda remains one of the poorest countries in SSA. Furthermore, due to the predominance of informal activities and weak tax administration system, the country collects only 13.7 % of its GDP in taxes. As such the amount of funds available for financing health services in general and reproductive health services in particular are limited.Item A Looming Crisis? An analysis of the health sector budget performance for the financial year 2012/13 and allocations for 2013/14(Initiative for Social and Economic Rights, 2013) Initiative for Social and Economic RightsOver the years, the government of Uganda has committed to improving the health sector service delivery through a number of interventions and policies. The health sector has been identified as one of the key priorities in the National Development Plan (NDP) and it contributes to all NDP objectives, although it is particularly focused on objective 4 - “Increasing access to quality social services". This is through provision and utilization of promotive, preventive, curative and rehabilitative services, and involves Strengthening Health Systems and ensuring universal access to the Uganda National Minimum Health Care Package (UNMHCP). The UNMHCP as provided for under the Health Sector Strategic Plan (HSSP) consists of the most costeffective priority healthcare interventions and services addressing the high disease burden that are acceptable and affordable within the total resource envelope of the sector. Universal access is one of the key underlying principles for delivery of the UNMHCP.Item Expanding HIVAIDS prevention programmes through Safe Male Circumcision and Voluntary Counselling and Testing in Uganda(2013) Ahaibwe, Gemma; Kasirye, Ibrahim; Barungi, MildredAlthough Uganda initially registered large reductions in HIV/AIDS prevalence rate during the 1990s, the rate of new HIV infection is on the rise across the country. At least 1.2 million Ugandans are infected with the HIV virus1 . Recent evidence from the 2011 Uganda AIDS Indicator Survey revealed that the HIV/AIDS prevalence rate had increased from 6.4 percent in 2004/5 to 7.3 percent by 20112. The trends in new HIV infections in figure 1 suggest that the annual number of new HIV infections increased by 11.4 percent from 115,775 in 2007/08 to 128,980 in 2010/11, despite the huge amounts of resources earmarked for HIV/AIDS related expenditures. The increase in the HIV/AIDS prevalence has been blamed on the complacency of Ugandans with the availability of anti-retrovaral therapies (ARTs)— especially regarding sexual behavior.Item Transcriptional Activity, Chromosomal Distribution and Expression Effects of Transposable Elements in Coffea Genomes(PLoS One, 2013) Lopes, Fabrıcio R.; Jjingo, Daudi; da Silva, Carlos R. M.; Andrade, Alan C.; Marraccini, Pierre; Teixeira, Joao B.; Carazzolle, Marcelo F.; Pereira, Goncalo A. G.; Pereira, Luiz Filipe P.; Vanzela, Andre´ L. L.; Wang, Lu; Jordan, I. King; Carareto, Claudia M. A.Plant genomes are massively invaded by transposable elements (TEs), many of which are located near host genes and can thus impact gene expression. In flowering plants, TE expression can be activated (de-repressed) under certain stressful conditions, both biotic and abiotic, as well as by genome stress caused by hybridization. In this study, we examined the effects of these stress agents on TE expression in two diploid species of coffee, Coffea canephora and C. eugenioides, and their allotetraploid hybrid C. arabica. We also explored the relationship of TE repression mechanisms to host gene regulation via the effects of exonized TE sequences. Similar to what has been seen for other plants, overall TE expression levels are low in Coffea plant cultivars, consistent with the existence of effective TE repression mechanisms. TE expression patterns are highly dynamic across the species and conditions assayed here are unrelated to their classification at the level of TE class or family. In contrast to previous results, cell culture conditions per se do not lead to the de-repression of TE expression in C. arabica. Results obtained here indicate that differing plant drought stress levels relate strongly to TE repression mechanisms. TEs tend to be expressed at significantly higher levels in non-irrigated samples for the drought tolerant cultivars but in drought sensitive cultivars the opposite pattern was shown with irrigated samples showing significantly higher TE expression. Thus, TE genome repression mechanisms may be finely tuned to the ideal growth and/or regulatory conditions of the specific plant cultivars in which they are active. Analysis of TE expression levels in cell culture conditions underscored the importance of nonsense-mediated mRNA decay (NMD) pathways in the repression of Coffea TEs. These same NMD mechanisms can also regulate plant host gene expression via the repression of genes that bear exonized TE sequences.Item Addressing Inequity and Discrimination in the Delivery of Health Services in Uganda(Economic and Social Rights Advocacy (ESRA), 2014) Kwemoi, CharlesHealth reports in Uganda are often characterized by aggregated statistical data showing progress on particular indicators such as maternal mortality, infant mortality, life expectancy, HIV/AIDS prevalence and so on. However, what the statistics fail to reveal are the individuals and groups of people excluded from the system, who are denied life saving services because of who they are or where they live. In applying a human rights perspective, it is imperative for policy makers to persistently peer behind the veil of lump-sum statistics and to test the universality and equitability of healthcare access and services. This is the second issue of the Economic and Social Rights Advocacy (ESRA) Brief published by the Initiative for Social and Economic Rights (ISER). The ESRA Brief is dedicated to Economic and Social Rights (ESRs) advocacy in Uganda but draws on key lessons from the broader East African Community. The Brief is intended for policy makers, civil society actors, development partners and the donor community as it provides insight into the debates and steps currently being undertaken by Ugandan organizations individually and collaboratively to achieve the full realization of ESRs.Item Mammalian-wide interspersed repeat (MIR)-derived enhancers and the regulation of human gene expression(Mobile DNA, 2014) Jjingo, Daudi; Conley, Andrew B.; Wang, Jianrong; Mariño-Ramírez, Leonardo; Lunyak, Victoria V.; Jordan, I. KingMammalian-wide interspersed repeats (MIRs) are the most ancient family of transposable elements (TEs) in the human genome. The deep conservation of MIRs initially suggested the possibility that they had been exapted to play functional roles for their host genomes. MIRs also happen to be the only TEs whose presence in-and-around human genes is positively correlated to tissue-specific gene expression. Similar associations of enhancer prevalence within genes and tissue-specific expression, along with MIRs’ previous implication as providing regulatory sequences, suggested a possible link between MIRs and enhancers. Results: To test the possibility that MIRs contribute functional enhancers to the human genome, we evaluated the relationship between MIRs and human tissue-specific enhancers in terms of genomic location, chromatin environment, regulatory function, and mechanistic attributes. This analysis revealed MIRs to be highly concentrated in enhancers of the K562 and HeLa human cell-types. Significantly more enhancers were found to be linked to MIRs than would be expected by chance, and putative MIR-derived enhancers are characterized by a chromatin environment highly similar to that of canonical enhancers. MIR-derived enhancers show strong associations with gene expression levels, tissue-specific gene expression and tissue-specific cellular functions, including a number of biological processes related to erythropoiesis. MIR-derived enhancers were found to be a rich source of transcription factor binding sites, underscoring one possible mechanistic route for the element sequences co-option as enhancers. There is also tentative evidence to suggest that MIR-enhancer function is related to the transcriptional activity of non-coding RNAs. Conclusions: Taken together, these data reveal enhancers to be an important cis-regulatory platform from which MIRs can exercise a regulatory function in the human genome and help to resolve a long-standing conundrum as to the reason for MIRs’ deep evolutionary conservation.