Bridging Bedside and Bench Translational Neuropsychiatry Research in Africa<br />DrLailaAsmal<br />University of Stellenbo...
Schizophrenia Research Overview<br />120 FEP participants (matched controls)<br />Treated with Flupenthixoldecanoate, 2 ye...
Translational Neuropsychiatry Research in Africa<br />
Bedside to bench and back<br />1.  Woolf SH, 2009<br />
Translational Neuropsychiatry Research in Africa<br />
Africa is not a country!<br />
But what do we have in common?<br />Wide-based age pyramid <br />Rural populations with recent but rapid urban migration<b...
Quadruple burden of disease<br />Pre-transitional diseases and poverty related conditions<br />childhood undernutrition an...
World Land Area<br />www.worldmapper.com<br />
Urban slums<br />www.worldmapper.com<br />
Undernourishment<br />www.worldmapper.com<br />
HIV Prevalence<br />www.worldmapper.com<br />
Syphilis deaths<br />www.worldmapper.com<br />
Epilepsy deaths<br />www.worldmapper.com<br />
Stroke deaths<br />www.worldmapper.com<br />
Translational NeuropsychiatryResearch in Africa<br />
What is Neuropsychiatry?<br />Mental disorders caused by:<br />Structural brain dysfunction<br />Electrical malfunction<br...
Challenges facing Neuropsychiatry Research in Africa<br />Studies in SSH are not easily accessible<br />Methodological con...
Dementia: a Developed World problem?<br />71% of dementia in developing countries by 20406<br />Prevalence is increasing i...
Dementia Developing Countries<br />6.  Kalaria J, 2008<br />
Case vignettes <br />
Alternate pathophysiology?<br />Poverty<br /><ul><li>Economic deprivation
Low education
Unemployment
Inadequate housing
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Asmal translational neuropsychiatry research

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  • ? For many, the termrefers to the “bench-to-bedside” enterprise of harnessingknowledge from basic sciences to produce new drugs, devices, and treatment options for patients. For this area ofresearch—the interface between basic science and clinicalmedicine—the end point is the production of a promisingnew treatment that can be used clinically or commercialized (“brought to market”). This enterprise is vital, and hasbeen characterized as follows: “effective translation of thenew knowledge, mechanisms, and techniques generated byadvances in basic science research into new approaches forprevention, diagnosis, and treatment of disease is essentialfor improving health.”
  • Panel: Common traits in sub-Saharan Africa A tropical location with near uniform climate with alternating wet and hot seasons that is remarkable for the complete absence of winter Wide-based age-specific pyramid with high fertility and mortality rates and short life expectancy: 50–60% of the population are children age &lt;15 years, rarely more than 5% are adults age &gt;50 years Mainly rural populations with recent but rapid rural to urban migration Widespread poverty and uneven distribution of infrastructure, financial, human and material resources in the health sector Absence of sound strategies for the collection and standardisation of data that make health statistics unreliable Social and political instability that leads to disorganisation of health services and sometimes emigration of populations Gross underdevelopment and unfavourable health conditions Presence of environmental factors (vectorial, toxic, infectious, mineral deficiencies, etc) with poorly understood causal association with epilepsy and progression of disease
  • pre-transitional diseases and poverty related conditions eg childhood undernutrition and infections, maternal mortality emerging chronic diseases eg obesity, heart disease, diabetes injuries - including interpersonal violence HIV/AIDS and TB epidemics (TB cases increased from 109,000 in 1996 to 341,165 in 2006. 55% cases also have HIV)
  • Studies in SSH are not easily accessible&gt;1/2 epilepsy studies published in regional journals with low distributions and are not indexed in the international databasesMethodological constraints and inconsistencies make epidemiological studies difficult to compare. The biggest constraint in these studies is data collection—clear endpoints are difficult to measure and representative populations hard to recruit. Screening questionnaires, typically used to identify patients with epilepsy, cannot be used across different populations with diverse social or cultural backgrounds; moreover medical records are commonly incomplete. The lack of specialised personnel, particularly in neurology, and the almost complete absence of diagnostic equipment (there are 75 EEGs and 25 CT scanners in tropical Africa, and these are frequently out of order), means that the accuracy of diagnosis cannot be confidently ascertained. The use of different terminologies to classify seizures and epilepsy also hinders study comparison.
  • In China, for example, 49% of patients with dementia were classified as normally ageing and only 21% had adequate access to diagnostic assessment,7 compared with 20% and more than 70%, respectively, in Europe.
  • Figure. Sporadic and familial dementias in developing countriesRed-shaded countries have prevalence or incidence estimates of all dementias that have beendetermined to be similar (&gt;5%) to those in developed countries (grey-shaded countries).Blue-shaded countries have significantly lower prevalence (&lt;3%) of dementia. Sample sizesfor the estimates in the various studies were between 700 and 3200 individuals. Green-shaded areas show countries where there are published cases of dementia or subtypes (ADor VaD), where risk factors have been examined but prevalence or incidence are unknown.Reliable information was not available for countries without shading. Red spots showlocations of families with neurodegenerative and vascular disorders causing dementiaincluding AD, Parkinson&apos;s disease, Lewy body disease, frontotemporal lobar degeneration,Huntington&apos;s disease, amyotrophic lateral sclerosis, and CADASIL. Information ondementia prevalence and types was derived from many sources.22,29,31,35,37–39,41,45,46,49– 52,58,62–73
  • Clearly progress has been made. A recent Lancet review[41] highlights both the growing awareness of the importance of dementia in developing countries and the burgeoning evidence base. Nevertheless, much more research is needed to close the 10/66 gap. There is still a need for a definitive multi-centric prevalence survey in India with true nationwide scope, encompassing regional, cultural, ethnic, religious, socioeconomic and rural/ urban diversity. Such a survey, whether or not it used the 10/66 methodology, would be enhanced by a common protocol in all centers, with a one phase design including the ascertainment of comorbid chronic diseases, disability, needs for care, care arrangements and health service utilization. It would provide a much needed baseline to monitor, in future surveys, trends in demographic ageing and the health transition. Also missing, for India, is any large-scale prospective study of risk factors for dementia, with biological samples (DNA, hematology, fasting glucose and lipids and frozen serum for later evaluation), other cardiovascular risk factor exposures, diet and anthropometry all collected at baseline. The 10/66 Dementia Research Group has succeeded in establishing such a study across our Latin American network and, to an extent in China, but not yet in India where the need is just as great. Finally, there is a great need, as indicated above, to develop packages and programs of care for people with dementia and their caregivers, which, their cost-effectiveness having been established, would be capable of being scaled up across India’s complex mixed healthcare system.
  • Asmal translational neuropsychiatry research

    1. 1. Bridging Bedside and Bench Translational Neuropsychiatry Research in Africa<br />DrLailaAsmal<br />University of Stellenbosch, Cape Town, South Africa<br />
    2. 2. Schizophrenia Research Overview<br />120 FEP participants (matched controls)<br />Treated with Flupenthixoldecanoate, 2 year follow-up<br />Predictors of outcome, course of illness, ethnic differences, structural brain changes<br />Confluence subsample<br />RCT, risperidone or flupenthixolimi<br />Structural and functional MRI changes<br />Stanley discontinuation study<br />Omega 3 and ALA<br />Other – cochrane, genetics, family therapy study, metabolic disease, early childhood trauma, criminality<br />
    3. 3. Translational Neuropsychiatry Research in Africa<br />
    4. 4. Bedside to bench and back<br />1. Woolf SH, 2009<br />
    5. 5. Translational Neuropsychiatry Research in Africa<br />
    6. 6. Africa is not a country!<br />
    7. 7. But what do we have in common?<br />Wide-based age pyramid <br />Rural populations with recent but rapid urban migration<br />Social and political instability<br />Widespread poverty and unevenly distributed health resources<br />Absence of sound strategies for data collection<br />Quadruple burden of disease<br />Preux PM, 2005<br />
    8. 8. Quadruple burden of disease<br />Pre-transitional diseases and poverty related conditions<br />childhood undernutrition and infections, maternal mortality<br />Emerging chronic diseases <br />obesity, heart disease, diabetes<br />Injuries<br />including interpersonal violence<br />HIV/AIDS, TB, malaria<br />MRC Burden of Disease Unit, 2004<br />
    9. 9. World Land Area<br />www.worldmapper.com<br />
    10. 10. Urban slums<br />www.worldmapper.com<br />
    11. 11. Undernourishment<br />www.worldmapper.com<br />
    12. 12. HIV Prevalence<br />www.worldmapper.com<br />
    13. 13. Syphilis deaths<br />www.worldmapper.com<br />
    14. 14. Epilepsy deaths<br />www.worldmapper.com<br />
    15. 15. Stroke deaths<br />www.worldmapper.com<br />
    16. 16. Translational NeuropsychiatryResearch in Africa<br />
    17. 17. What is Neuropsychiatry?<br />Mental disorders caused by:<br />Structural brain dysfunction<br />Electrical malfunction<br />Extrinsic toxic-metabolic derangements<br />Emphasises neurological basis of mental illness<br />Utilises modern neurodiagnostic investigations in evaluation and treatment <br />Hurwitz M, 2009<br />
    18. 18. Challenges facing Neuropsychiatry Research in Africa<br />Studies in SSH are not easily accessible<br />Methodological constraints make epidemiological studies difficult to compare. <br />Clear endpoints difficult to measure<br />Questionnaires not suitable for diverse populations<br />Medical records are commonly incomplete<br />Lack of specialised personnel, diagnostic equipment <br />Use of different terminologies to classify disorders. <br />Preux, 2005<br />
    19. 19. Dementia: a Developed World problem?<br />71% of dementia in developing countries by 20406<br />Prevalence is increasing in developing countries5<br />Confounders5: <br />shorter survival, lack of awareness, inadequate diagnostic assessments, variability of costs of care – under-reporting<br />Research focus on elderly population<br />Some work on HIV<br />Kalaria R, 2008<br />Prince M, 2009<br />
    20. 20. Dementia Developing Countries<br />6. Kalaria J, 2008<br />
    21. 21. Case vignettes <br />
    22. 22. Alternate pathophysiology?<br />Poverty<br /><ul><li>Economic deprivation
    23. 23. Low education
    24. 24. Unemployment
    25. 25. Inadequate housing
    26. 26. Lack of basic eminities
    27. 27. Overcrowding</li></ul>Dementia<br /><ul><li>Higher prevalence
    28. 28. Earlier onset
    29. 29. Poor/lack of care
    30. 30. More severe course
    31. 31. Infectious diseases
    32. 32. High stressors
    33. 33. Inadequately treated depression
    34. 34. Reduced access to social capital
    35. 35. Malnutrition
    36. 36. Obstetric risks
    37. 37. Epilepsy
    38. 38. Violence and trauma</li></li></ul><li>Layering of risk factors<br />Dementia<br />
    39. 39. What do we need?<br />Multi-centric prevalence survey across Africa<br />Sufficient participantsencompassing diversity <br />Common protocol<br />Focus on co-morbidity<br />Carer, need for care, disability, health care use<br />Biological samples (DNA, haematology, fasting glucose and lipids and frozen serum)<br />Longitudinal studies to better estimate incidence, morbidity, and mortality. <br />Dissemination of knowledge<br />
    40. 40. References<br />Woolf SH. JAMA, Jan 2008; 299(2) The Meaning of Translational Research and why it matters: 211-213<br />Preux PM, Druet-CabanacM. Epidemiology and aetiology of epilepsy in sub-Saharan Africa. Lancet Neurol 2005; 4: 21–31<br />MRC Burden of Disease Unit, 2004<br />www.worldmapper.com<br />Hurwitz, Fundamentals of Neuropsychiatry, UBC, 2009<br />Kalaria et al. Alzheimer'sdisease and vasculardementia in developing countries: prevalence, management, and riskfactors. Lancet Neurol. 2008 Sep; 7(9): 812–826. <br />Prince MJ, The 10/66 dementia research group - 10 years on. Indian J Psychiatry. 2009 January; 51(Suppl1): S8–S15. <br />
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