Makerere University Kampala is Uganda's largest and third-oldest institution of higher learning, first established as a technical school in 1922 , and is now part of Uganda Christian University. In 1963, it became the University of East Africa, offering courses leading to general degrees from the University of London. It became an independent national university in 1970 when the University of East Africa was split into three independent universities: University of Nairobi , University of Dar es Salaam , and Makerere University. Today, Makerere University is composed of 9 Colleges and one school offering programmes for about 36,000 undergraduates and 4,000 postgraduates.Makerere was home to many post-independence African leaders, including former Ugandan president Milton Obote and late Tanzanian president Julius Nyerere. Former Tanzanian president Benjamin Mkapa current president of the DRC Joseph Kabila and the former Kenyan President Mwai Kibaki are also Makerere alumni.In the years immediately after Uganda's independence, Makerere University was a focal point for the literary activity that was central to African nationalist culture. Some prominent writers, including Nuruddin Farah, Ali Mazrui, David Rubadiri, Okello Oculi, Ngũgĩ wa Thiong'o, John Ruganda, Paul Theroux, V. S. Naipaul and Peter Nazareth, were at Makerere University at one point in their writing and academic careers. Wikipedia.
News Article | April 17, 2017
Successful clinical trials to create drugs and vaccines for next pandemic disease will rely on building capacity, community engagement, and international collaboration before and during outbreak WASHINGTON - Mobilization of a rapid and robust clinical research program that explores whether investigational therapeutics and vaccines are safe and effective to combat the next infectious disease epidemic will depend on strengthening capacity in low-income countries for response and research, engaging people living in affected communities, and conducting safety trials before an epidemic hits, says a new report from the National Academies of Sciences, Engineering, and Medicine. Using key lessons learned from the Ebola epidemic in West Africa, the report outlines how to improve the speed and effectiveness of clinical trial research while an epidemic is occurring, especially in settings where there is limited health care and research infrastructure. The research and development of therapeutics and vaccines is a long, complex, and expensive process and cannot be compressed into the course of a rapidly progressing outbreak. The development of a drug "from bench to bedside" is estimated, on average, to take at least 10 years and cost $2.6 billion, with less than 12 percent likelihood of eventual licensing. Therefore, making progress on the research and development of products - such as therapeutics and vaccines - before an epidemic breaks is the only way to ensure that promising candidates are ready for trials once an outbreak occurs, said the committee that carried out the study and wrote the report. In addition, clinical trials could be more rapidly planned, approved, and implemented during an outbreak if promising products are studied through Phase 1 or Phase 2 safety trials in advance of an outbreak and if emergency response planning includes clinical research considerations and clinical researchers in the discussions from the beginning. The 2014-2015 Ebola epidemic was the longest and most deadly Ebola outbreak since the virus was first discovered in 1976, resulting in 28,616 cases and 11,310 deaths in Guinea, Liberia, and Sierra Leone. In August 2014, the World Health Organization declared the epidemic a public health emergency of international concern. Researchers discussed how to conduct clinical trials on potential Ebola therapeutics and vaccines in West Africa, and ultimately, several teams conducted formal clinical trials in the Ebola-affected countries during the outbreak. The clinical trial teams overcame immense logistical obstacles encountered while trying to design and implement trials in West Africa in the midst of a rapidly spreading epidemic of a highly dangerous contagious disease. However, none of the therapeutic trials ended with conclusive results on product efficacy, although limited evidence from the trial for the ZMapp treatment did trend toward a possible benefit. Given the resources, time, and effort put into these trials, they were not as successful as they could have been. The results of the vaccine trials were more fruitful. Two Ebola vaccine candidates have data that suggest they may be safe and produce an immune response, and one is most likely protective, but further data are needed. Planning and conducting clinical research during the Ebola epidemic also required confronting a number of ethical issues, such as whether it was ethical to conduct clinical trials at all in the midst of a public health emergency and whether the research activities drew effort away from providing clinical care to the most people possible. There was also disagreement among researchers over how clinical trials should be designed during the Ebola epidemic, particularly whether trials should use randomization and concurrent control groups. Randomized controlled trials are generally the preferred research design, because they allow researchers to directly compare the outcomes of similar groups of people who differ only in the presence or absence of the investigational agent. However, many argued that randomized controlled trials would be unethical during the Ebola epidemic, as this trial design would deprive patients of an agent that could potentially prevent or treat Ebola, given the high mortality rate and lack of known and available treatment options. The committee concluded that randomized controlled trials are both ethical and the fastest and most reliable way to identify the relative benefits and risks of investigational products, and except in rare circumstances, every effort should be made to implement them during epidemics. The issues that influenced choices about trial design during the Ebola epidemic - such as community mistrust, the feasibility of a standard-of-care-only arm, the high and variable mortality rate, limited product availability, and the potential conflicts between research and care - are likely to recur in future epidemics. Nevertheless, the perceived ethical or logistical hurdles that these issues present are not sufficiently compelling to override the benefits of randomized trials. Rather, randomized trials may be the most ethical trial design, because they offer the fastest route to identifying beneficial treatments while minimizing the risks of exposure to potentially harmful investigational agents. To improve the national and international clinical trial response to the next epidemic, the committee focused on three main areas - strengthening capacity, engaging communities, and facilitating international coordination and collaboration - both in the period of time before an outbreak strikes and during the epidemic itself. The committee found major capacity challenges that hindered and slowed the research response to the Ebola epidemic, and recommended developing sustainable health systems and research capabilities, improving capacity to collect and share clinical and epidemiological data, facilitating the mechanisms for rapid ethics reviews and legal agreements before an epidemic occurs, and incorporating research systems into emergency preparedness and response systems for epidemics. Affected communities had considerable fear, mistrust, and misunderstanding of national and international response and research staff. Community members feared going to health care facilities for the treatment of Ebola, rumors spread that Ebola was deliberately brought to the region by foreigners, and initial response efforts did not take into account community traditions and beliefs. For example, mandatory cremation policies countered deeply held religious beliefs. Successful clinical research is dependent on a community's understanding of, engagement in, and sense of involvement and respect in the process of planning and conducting research, the committee found. Community engagement should be prioritized during epidemic responses and be a continuous and evolving effort, starting at the onset of the epidemic. Research and response efforts were also greatly affected by the relationships among international stakeholders and their ability to coordinate and collaborate. For example, there were a few Ebola-specific therapeutic candidates with suggestive efficacy available at the beginning of the outbreak that could have been investigated in clinical trials, but the mechanism to prioritize which should be studied first was limited. The committee recommended the establishment of an international coalition of stakeholders to work between epidemics that would advise and prioritize pathogens to target for research and development, develop generic clinical trial design templates, and identify teams of clinical research experts who could be deployed to assist with research during an outbreak. The committee also highlighted seven critical steps to launching successful clinical trials when the next epidemic first strikes and before it peaks. The steps are to collect and share patient information and establish standards of care, engage communities and establish mutual trust, integrate research efforts into response and facilitate stakeholder coordination, prioritize vaccines and therapies and select trial designs, negotiate contracts, consult with regulators, and perform independent ethics reviews. The study was sponsored by the U.S. Department of Health and Human Services' Office of the Assistant Secretary for Preparedness and Response, National Institutes of Health, and U.S. Food and Drug Administration. The National Academies of Sciences, Engineering, and Medicine are private, nonprofit institutions that provide independent, objective analysis and advice to the nation to solve complex problems and inform public policy decisions related to science, technology, and medicine. The National Academies operate under an 1863 congressional charter to the National Academy of Sciences, signed by President Lincoln. For more information, visit http://national-academies. . A roster follows. Copies of Integrating Clinical Research Into Epidemic Response: The Ebola Experience are available from the National Academies Press at http://www. or by calling 1-800-624-6242. Reporters may obtain a copy from the Office of News and Public Information (contacts listed above). Gerald T. Keusch, M.D.* (co-chair) Professor of Medicine and Global Health Boston University Schools of Medicine and Public Health Boston Keith McAdam, M.D. (co-chair) Emeritus Professor of Clinical and Tropical Medicine London School of Hygiene and Tropical Medicine London Abdel Babiker, Ph.D. Professor of Epidemiology and Medical Statistics Medical Research Council Clinical Trials Unit at University College London London Susan S. Ellenberg, Ph.D. Professor of Biostatistics Perelman School of Medicine University of Pennsylvania Philadelphia Roger J. Lewis, M.D., Ph.D.* Professor and Chair of the Department of Emergency Medicine Harbor-UCLA Medical Center Los Angeles Alex London, Ph.D. Professor of Philosophy, and Director of the Center for Ethics and Policy Carnegie Mellon University Pittsburgh Michelle M. Mello, Ph.D.* Professor of Law Stanford University School of Medicine and School of Law Stanford, Calif. Olayemi Omotade, M.D. Professor of Pediatrics and Child Health Institute of Child Health University College Hospital University of Ibadan Ibadan, Nigeria Fred Wabwire-Mangen, Ph.D. Associate Professor of Epidemiology and Public Health Makerere University School of Public Health Kampala, Uganda
News Article | April 11, 2017
Zika Virus - What You Should Know Ebola - What You Should Know Elephantiasis is a painful and debilitating condition typically caused by a microscopic parasitic worm about the width of a human hair. This worm becomes embedded in the host's lymph nodes, resulting in an accumulation of bodily fluid that would normally be drained by the lymphatic system. This form of elephantiasis, called lymphatic filariasis, is spread from person to person through mosquito bites and leads to swollen limbs, thickened skin, ulcers, and infections. According to the U.S. Centers for Disease Control and Prevention, lymphatic filariasis is one of the leading causes of permanent disability worldwide. This disfiguring disease leaves people unable to work to sustain themselves or even move easily. A recent outbreak of elephantiasis in western Uganda was found, however, to be originated by something else. After failing to discover any traces of the worm, researchers from the Makerere University in Kampala, Uganda, working together with the Uganda Ministry of Health, the World Health Organization, and the CDC, observed that the affected patients had only one thing in common: a history of farming in volcanic soil without wearing shoes. The new cases of elephantiasis were identified in a remote community living at an altitude of 4,000 feet in the foothills of the Kamwenge District. Until now, this region hadn't been flagged as a risk area for the inflammatory disease. This dry region, which is only showered by roughly 4 feet of rain throughout the year, has a particular type of soil, made up of fragmented volcanic rocks dating back 2.5 million years ago. This volcanic soil retains irritant mineral crystals that can penetrate the skin, causing itching, pain, scarring, and swelling in repeated cycles of inflammation. Locals from the isolated village attested to working barefoot on their farms, which led researchers to believe all 52 patients were in fact suffering from podoconiosis, another form of the disease. Triggered by prolonged exposure of the soles to volcanic soil, this type of elephantiasis produces a build-up of scar tissue that eventually blocks lymphatic vessels, resulting in heavy swelling and open sores in the lower legs. The researchers detailed their findings in a paper, published April 10 in The American Journal of Tropical Medicine and Hygiene. Podoconiosis is not an infectious disease and its early symptoms (pain, itching, and swelling) are easily dismissed as normal signs of exertion consistent with working on a farm. This means "people can be suffering from podoconiosis for decades before it becomes obvious that they are developing elephantiasis," explains Christine Kihembo, study lead author and epidemiologist at Makerere University, in a statement. Kihembo, who also works with the Ugandan Ministry of Health, believes these farmers have been "probably suffering silently without help for more than 30 years," ever since they moved in the area and became exposed to the volcanic soil. WHO reports the disease is widely spread across Africa, with at least a million documented cases in Ethiopia and more than half a million in Cameroon. The surest way to prevent podoconiosis is regular foot hygiene, doubled by wearing shoes at all times. Nevertheless, proper care can be difficult to follow in poor, rural areas, notes Kihembo, who admits that people living in these communities face "many hardships, and going barefoot is not generally viewed as one of them." The stigma of this condition fuels even more isolation, and lack of information on the causes of the disease leaves podoconiosis undiagnosed and untreated. The people affected by it are at risk of developing "secondary infections due to the ulcers on the skin," accelerating the decline of their health. To raise awareness about podoconiosis detection and treatment, a public health education campaign is now underway in the region, to inform locals about the importance of better foot hygiene. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.
Agency: European Commission | Branch: H2020 | Program: CSA | Phase: INFRASUPP-6-2014 | Award Amount: 2.04M | Year: 2015
B3Africa - Bridging Biobanking and Biomedical Research across Europe and Africa will dramatically improve and facilitate the development of better predictive, preventive and personalized healthcare worldwide. The rapidly evolving African biobanks are an invaluable resource: The African population has the greatest genomic diversity on the planet and represents an incredible resource of information to advance biomedical research. B3Africa aims to implement a cooperation platform and technical informatics framework for biobank integration between Africa and Europe. The collaboration harmonizes the ethical and legal framework, biobank data representation and bioinformatics pipelines for sharing data and knowledge among biobanks and allowing access for researchers from both continents. Main actors from the relevant initiatives including Human Heredity and Health in Africa project (H3Africa), European Biobanking and Biomolecular Resources research infrastructure (BBMRI-ERIC) and LMIC Biobank and Cohort Network (BCNet) collaborate in B3Africa to address the following objectives: Defining an ethical and regulatory framework for biobank data sharing between Europe and Africa Defining data models for representing biobank and research data based on existing best practices, standards and ontologies Designing an informatics platform using existing open-source software (with eBioKit and BiBBox as essential modules) integrating workflows for biobank applications Implementation of an education and training system for information and capacity building Validating the B3Africa concept with existing biobanks from both continents B3Africa will provide the critical mass to maximise efficiency in biomedical research, supports defragmentation through integration and allows efficient leverage of existing biobanks and e-infrastructures in Europe and Africa. The technical informatics framework will be designed for easy upscaling and integration with other research infrastructures.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: WATER-5c-2015 | Award Amount: 3.57M | Year: 2016
The WHO estimates that in 2015 in Africa ~156 million people relied on untreated sources for their drinking water. WATERSPOUTT will design, develop, pilot and field-test a range of, sustainable point-of-use solar disinfection (SODIS) technologies that will provide affordable access to safe water to remote and vulnerable communities in Africa and elsewhere. These novel large-volume water treatment SODIS technologies will be developed in collaboration and consultation with the end-users, and include: 1. HARVESTED RAINWATER SODIS SYSTEMS for domestic and community use. (South Africa, Uganda). 2. TRANSPARENT 20L SODIS JERRYCANS. (Ethiopia) 3. COMBINED 20L SODIS/CERAMIC POT FILTRATION SYSTEMS. (Malawi) These are novel technologies that will create employment and economic benefits for citizens in both the EU and resource-poor nations. WATERSPOUTT will use social science strategies to: a. Build integrated understanding of the social, political & economic context of water use & needs of specific communities. b. Examine the effect of gender relations on uptake of SODIS technologies. c. Explore the relevant governance practices and decision-making capacity at local, national and international level that impact upon the use of integrated solar technologies for point-of-use drinking water treatment. d. Determine the feasibility & challenges faced at household, community, regional and national level for the adoption of integrated solar technologies for point-of-use drinking water treatment. WATERSPOUTT will transform access to safe drinking water through integrated social sciences, education & solar technologies, thus improving health, survival, societal well-being & economic growth in African developing countries. These goals will be achieved by completing health impact studies of these technologies among end-user communities in Africa. Many of the consortium team have worked for more than 15 years on SODIS research in collaboration with African partners.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: HCO-06-2015 | Award Amount: 2.99M | Year: 2015
FRESH AIR is a 3 year project which addresses the urgent need to prevent, diagnose and treat lung diseases in LMICs and other low-resource settings where the greatest burden of disease is experienced. Our Consortium brings together leading international respiratory researchers, clinicians and policy experts from EU member states and the US who have expertise and experience of the challenges of implementation in LMICs and healthcare providers, policy makers and implementers from four countries that represent very different low-resource settings. Members will work together to adapt and test innovation and evidence-based practice in the prevention, diagnosis and treatment of lung disease in four low-resource settings in Uganda, Kyrgyz Republic, Vietnam and Greece with high levels of tobacco consumption and exposure to Household Air Pollution (HAP). In so doing, the Consortium will transfer skills and technology from EU member states and the US to new contexts and explore a range of implementation science research questions. The new knowledge this generates will be widely disseminated nationally, regionally and internationally, ensuring the scale-up of interventions tested by the project and global impact of research findings. The project will also provide new perspectives on policy issues of concern to EU members, increase the international profile of EU funded research on key health challenges and open up markets for healthcare innovations. The project has 7 specific objectives focused on the following: 1. Identifying factors influencing the implementation of evidenced-based interventions 2. Exploring which awareness-raising approaches are most effective in achieving behaviour change 3. Adapting interventions that provide smoking cessation support 4. Testing innovative diagnostic methods for COPD 5. Promoting pulmonary rehabilitation as a low cost treatment 6. Reducing childrens risk of lung damage 7. Generating new knowledge, innovation and scalable models.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-21-2016 | Award Amount: 7.69M | Year: 2017
The new challenge in global health is to achieve Universal Health Care (UHC) by 2030. Having an adequate workforce is critical to achieving UHC. Efforts are in place to scale up the numbers of health workers. Improving health workforce performance is equally important as the quantity of health workers, but more challenging. Workforce performance improvement can be achieved better at management levels close to front-line workers. The PERFORM project developed a problem-based management strengthening intervention for management teams at district level in three African countries to improve both health workforce performance and service delivery more generally. The evaluation of the management strengthening intervention (MSI) demonstrated its effectiveness in enabling the management teams to solve workforce performance and other problems locally which improved service delivery, and become better managers. To have a wider impact and thus contribute to the achievement of UHC the PERFORM management strengthening intervention needs to be scaled up and embedded. The aim of PERFORM2scale is to develop and evaluate a sustainable approach to scaling up a district level management strengthening intervention in different and changing contexts. A framework and strategy for scaling up the intervention will be developed with government agencies in Ghana, Malawi and Uganda each country. Capacity will be developed to implement the scale-up which will be carried out over three years in order to use the MSI at scale and embed the process at district level. The scale-up framework and strategy will be subjected to process evaluation (to identify opportunities and barriers) and outcome evaluation. Both the framework and strategy will be validated for use in the study countries and elsewhere for use and adaptation. The use of the management strengthening intervention at scale in countries will be a major contribution to achieving UHC.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SFS-15-2014 | Award Amount: 8.82M | Year: 2015
PROTEIN2FOODs aim is to develop innovative, cost-effective and resource-efficient plant proteins rich food sources with positive impact on human health, the environment and biodiversity. The quality and quantity of protein from selected highly nutritious seed crops (quinoa, amaranth and buckwheat), and legumes with high protein quantity (lupin, faba beans, pea, chickpea, lentil) will be significantly enhanced by using a multi-disciplinary approach that will include genetic, agronomic, food process engineering, sensory, socio-economic, and environmental assessment. Research is expected to improve the quality of plant proteins, produced in Europe, and of the sustainability of their production and processing. Through a better understanding of the: i) genetic mechanisms driving the protein formation and accumulation in the seed, ii) plant performance towards biotic and abiotic stresses, and iii) protein interactions with other components in the food matrix and its sensory repercussions in the final food products, this research should lead to the development of adapted plant protein sources with positive impact on environment and biodiversity as well as human health. Expected results in the project are: i) enhance the protein production by 25% through new effective breeding techniques and optimised crop management with an increase by 10% of the EUs arable land destined to protein-crop production, using also marginal soils, ii) accelerate protein transition from animal-based protein to plant based protein in Europe with clear impact on reduction of carbon footprint, iii) increase EU agro-biodiversity by introducing promising high quality crops and legumes. Further, activities will support the prototypes of new protein-rich-protein food with exceptional market potential. Finally, we will improve the EUs visibility in the area of food processing and technology through high impact factors scientific publications.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-21-2016 | Award Amount: 5.90M | Year: 2017
The overall research objective of the SPICES project is to implement and evaluate a comprehensive CVD prevention and control program in five settings: a rural & semi-urban community in a low-income country (Uganda), middle income (South Africa) and vulnerable groups in three high-income countries (Belgium, France and United Kingdom) as well as to identify and compare the barriers and facilitators across study contexts. The project will be evaluated using a mix of formative assessments; pre/post and trial designs. At the beginning of the project, we will conduct baseline assessments including literature reviews, formative studies, household surveys (where feasible) and learn lessons from other projects to understand healthcare and lifestyle practices, barriers, and facilitators. A cost-effectiveness and cost benefit analysis will be included. In addition, the teams will conduct site exchanges visits to learn from each other and organise policy dialogues to ensure sustainability and maximise impact of the interventions. The implementation outcomesacceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, coverage, and sustainability will be evaluated in order to understand the factors affecting the implementation, the processes, and the accruing results. The intervention of the SPICES project will aim to: (1) improve patients risk profiles (LDL-cholesterol, blood pressure, HbA1c (among patients with diabetes), modify lifestyles (diet and exercise and smoking cessation) and achieve recommended cholesterol, blood pressure and glycaemic control targets; (2) increase proportion of patients receiving appropriate BP, cholesterol and diabetes medication; (3) and mitigate the number of people developing complications such a stroke and myocardial infarction.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: HCO-05-2014 | Award Amount: 3.34M | Year: 2015
Background: Type 2 diabetes mellitus (T2DM) and pre-diabetes contribute increasingly to the global burden of disease with the health systems struggling to effectively manage prevention and control. This necessitates contextually appropriate, policy relevant solutions with high scale-up potential. The study is built on a consortium experienced in implementation and cross-cultural translation of disease prevention and management. We aim to strengthen capacity for T2DM care including prevention in high-risk population, through proven strategies like task shifting to community health workers, and expanding care networks through community-based peer support groups. Methods: A phased, participatory approach with built-in on-going policy dialogue will be used for implementing and testing a complex intervention in three countries representing low-, middle- and high-income settings: rural Uganda, urban South Africa and vulnerable immigrant populations in urban Sweden. These actions will follow an iterative process with modifications and improvements within and between the stages of formative research to implementation and evaluation. The testing will be conducted with a controlled design in two arms, a facility-only strategy vs. a combined facility and community strategy evaluated in terms of health systems, disease-related and equity outcomes. Outcomes: The study has a strong social innovations component that will leverage existing networks and platforms, to empower patients, their families and communities through the self-management approach. It will embed research into policy and practice from the beginning; and enable cross-lessons from other chronic conditions and reciprocal learning. It will re-introduce the essential but missing community component still existing in low- and middle-income countries back to the health system of a high-income country in a contextually appropriate form, which is relevant for Europe in tackling T2DM and other chronic conditions.
Agency: GTR | Branch: MRC | Program: | Phase: Research Grant | Award Amount: 888.67K | Year: 2015
Cryptococcal meningitis (CM) is a major causative agent of fungal meningitis worldwide. In sub-Saharan Africa, cryptococcal meningitis is the most common cause of meningitis in adults and causes 20-25% of AIDS-related mortality. The excessive early mortality from cryptococcosis is in large part due to the high cost, toxicity, and relatively limited repertoire of available anti-fungals, which have changed little in the last 30 years. For these reasons, the identification of new anti-fungals effective for the treatment of fungal meningitis must be a high priority. One problem with many current anti-fungal drugs is that they penetrate poorly into the brain. This is a particularly difficult problem in treating fungal meningitis, which is an infection around the brain. New research suggests that sertraline, one of the most widely prescribed antidepressants in the world, has anti-fungal activity against Cryptococcus. The findings are the result of investigations testing sertraline against Cryptococcus neoformans in culture, in a mouse model of infection, and in studies of its mechanism of action which appear to be inhibiting protein synthesis in the Cryptococcus yeast. Sertraline is known to be well-tolerated and is effective as an antidepressant. Preliminary investigations of sertraline in a mouse model of systemic cryptococcal infection revealed that it combats infection with efficacy similar to fluconazole, an oral anti-fungal drug used commonly for fungal disease since 1990. Most importantly, the combination of sertraline and fluconazole was found to work better than either drug alone. Sertraline is concentrated in the brain (average of 22-fold over blood levels), and thus may be an ideal oral medicine to add to standard therapy for cryptococcal meningitis. Despite these promising initial studies, no studies have been conducted in actual humans. This study seeks to help answer these questions. The research team, based in Uganda, plans to determine whether the addition of sertraline to standard therapy for CM will result in more rapid clearance of the fungal infection. An This project will have two phases. An initial pharmacokinetic dose finding and safety study was conducted Aug 2013-Feb 2014 which has informed the sertraline dosing choices, confirmed the general tolerability, and provided preliminary data that the rate of clearance of yeasts from the cerebrospinal fluid (termed early fungicidal activity) is approximately 25% faster over the first two weeks than current standard therapy. This proposal is for support of a multisite, Phase III study to determine whether sertraline improves survival in comparison to placebo. All research participants will receive standard anti-fungal therapy of amphotericin + fluconazole as induction therapy. The implications of this research are clear. Since strong safety data already exists, investigation into the use of sertraline as anti-fungal is greatly accelerated. If sertraline proves to be effective in treatment of Cryptococcus in humans, it would be immediately available for use, essentially creating a shortcut from bench to bedside. This would result in huge cost savings compared to bringing an entirely new drug to the market. Sertraline could have the potential to revolutionize cryptococcal care in Sub-Saharan Africa as it is an existing low cost, generic medicine made by >=25 manufacturers worldwide.