Epilepsy in sub-Sahran Africa : analysis of excess mortality in epilepsy and associated risk factors from cohort studies

Epilepsy is a disorder of the brain manifested with the recurrent unprovoked seizures. It affects about 71 million people globally. Epileptic seizures may involve a sudden loss of conscious, rapid muscles rigidity and contractions, violent convulsions and falls if a person is standing or sitting. Epilepsy can be controlled by antiepileptic drugs (AEDs) and adherence to treatment has been shown to improve quality of life, reduce seizure frequency, injuries, and death. Epileptic seizures negatively impact the lives of people with epilepsy (PWE) and those around them especially in LMIC. It is estimated that 80% of PWE live in LMICs. Excess mortality in PWE in developed countries is estimated to be up to 2 times higher than general population. There is scant data on excess mortality in PWE in SSA. Scarcity of evidence on the impact of epilepsy has resulted in PWE being marginalized in health services planning and provision despite having high psychological, economic, morbidity and mortality burden relative to the general population. This thesis provides needed knowledge on uncertainties of epilepsy in SSA in relation to mortality, risk factors, and causes of death in PWE. The knowledge and evidence were generated from five studies using empirical data from community-based studies. Systematic review The first thesis objective was aimed at reviewing and summarizing available evidence on excess mortality in PWE compared to general population in LMIC. Systematic review in Chapter 3 identified only 7 studies in LMIC over the period of 25 years. Estimated excess mortality of ranged from 1.3-7.2 times higher in PWE than general population (median=2.6). Meta-analysis of this systematic review indicated that up to 80% of total variability’s in the estimate of excess mortality (SMR) was only due to differences between studies. These differences may be due to methodological variations between studies or other unknown factors. The estimated excess mortality of 2.6 was median value and not pooled estimate as large variability’s between studies could not allow combined estimate of 7 studies. In conclusion, until this systematic review was done, there were no sufficient data to provide empirical evidence of excess mortality in PWE in LMIC. SEEDS study: Excess mortality At the time the systematic review was completed, new data on mortality of PWE were emerging from SEEDS studies. SEEDS studies had already followed PWE for over 8 years and documented deaths in people with and without epilepsy. Chapter 4 of this thesis was dedicated at pooling and generating new evidence of excess mortality in PWE from SEEDS studies. The pooled excess mortality was 4.8 times higher in PWE than general population (95% CI: 4.2-5.6). SEEDS estimate is higher than summary findings from systematic review in reported in the literature in Chapter 4. SEEDS studies were conducted to account for methodological limitations encountered in most epilepsy studies related to screening, diagnosis, mortality and causes of death assessment, and population representativeness. SEEDS study: Risk factors The studies also identified modifiable risk factors potential for intervention programs and mitigating the negative impact of epilepsy. Causes of death automation In addition to summarizing excess mortality in PWE, systematic review in Chapter 3 summarized causes of deaths in PWE from different studies. Summary estimates from different studies in LMIC indicated most PWE died of direct causes which are status epilepticus (SE) and sudden death in epilepsy (SUDEP) and indirect (injuries) causes of epilepsy death. These studies compiled causes of death information from variety of sources including physicians, verbal autopsies and death certificates. In Chapter 5, this thesis assessed the application of automated tools in ascertaining causes of death in PWE. The assessment indicated that, the use of automated tools is potentials, convenient and affordable alternative to post-mortem and physician death certification. Unlike the use of other sources of cause of death information, automated tool estimated lower number of epilepsy-related deaths (27.5%) compared to around 50% when physician make diagnosis of cause of death. Chapter 5 also provides valuable information and recommendation needed for further development and refinement of these tools especially with regards to coding SUDEP, SE, and injuries. National estimates Chapter 6 and 7 provides national and community-based estimates of mortality of epilepsy and other neurological disorders from national (SAVVY) and community-based studies (HDSS). The findings indicate epilepsy the second leading cause of death after cerebrovascular disorders. The estimates of mortality rate in the population ranged from 7-8 and 4-8 deaths per 100,000 populations in SAVVY and HDSS respectively. HDSS data HDSS sites have become platform for monitoring demographic indicators in most SSA. Analysis of HDSS data was aimed at ascertaining whether there has been declining trends in epilepsy and other neurological disorders over time. In Chapter 7 of this thesis, results of the analysis indicated epilepsy mortality did not change over the past 15 years. Synthesis This thesis generated new insights into the epidemiology of epilepsy in SSA. Limited data of studies of burden of epilepsy mortality in SSA point to either lack of interest in the subject, resources limitations from governments and funding bodies, and lack of knowledge of the negative impact of epilepsy. This study provides vigorous evidence of excess mortality needed for advocacy to health care providers, governments, and funding bodies for increased investment in care, preventions and reduction of the negative impact of epilepsy in SSA. The community and health care providers will benefit from evidence on modifiable risk factors for incidence and excess mortality from SEEDS study

Antiretroviral Treatment Knowledge and Stigma--Implications for Programs and HIV Treatment Interventions in Rural Tanzanian Populations.

To analyse antiretroviral treatment (ART) knowledge and HIV- and ART-related stigma among the adult population in a rural Tanzanian community. Population-based cross-sectional survey of 694 adults (15-49 years of age). Latent class analysis (LCA) categorized respondents' levels of ART knowledge and of ART-related stigma. Multinomial logistic regression assessed the association between the levels of ART knowledge and HIV- and ART-related stigma, while controlling for the effects of age, gender, education, marital status and occupation. More than one-third of men and women in the study reported that they had never heard of ART. Among those who had heard of ART, 24% were east informed about ART, 8% moderately informed, and 68% highly informed. Regarding ART-related stigma, 28% were least stigmatizing, 41% moderately stigmatizing, and 31% highly stigmatizing toward persons taking ART. Respondents that had at least primary education were more likely to have high levels of knowledge about ART (OR 3.09, 95% CI 1.61-5.94). Participants highly informed about ART held less HIV- and ART-related stigma towards ART patients (OR 0.26, 95% CI 0.09-0.74). The lack of ART knowledge is broad, and there is a strong association between ART knowledge and individual education level. These are relevant findings for both HIV prevention and HIV treatment program interventions that address ART-related stigma across the entire spectrum of the community

Mortality of neurological disorders in Tanzania: analysis of baseline data from sample vital registration with verbal autopsy (SAVVY)

Background: Neurological disorders (ND) have a profound consequence on human productivity, quality of life and survival. There are limited data on the burden of ND in Tanzania due to insufficient coverage of civil and vital registration systems.; Objectives; : This study was conducted to estimate mortality of ND in all ages in Tanzania using data from the Sample Vital Registration with Verbal Autopsy (SAVVY) study.; Methods; : Multistage random sampling was employed to select 23 districts, 1397 census enumeration areas and 154,603 households. During the baseline survey conducted between 2011 and 2014, deaths which occurred 12 months prior to the baseline survey were documented followed by verbal autopsy interviews. Causes of death were certified using International Classification of Diseases.; Results; : The baseline survey enrolled a total of 650,864 residents. A total of 6645 deaths were reported to have occurred 12 months before the date of survey. Death certification was available for 5225 (79%) deaths. The leading causes of death were cerebrovascular diseases with a cause-specific mortality fraction (CSMF) of 1.64% (95% CI: 1.30-1.99) and 3.82% (95% CI: 2.92-4.72) in all ages and adults older than 50 years, respectively. Stroke accounted for 92% of all cerebrovascular deaths. Mortality of epilepsy was estimated with a CSMF of 0.94% (95% CI: 0.68-1.20); meningitis with a CSMF of 0.80% (95% CI: 0.56-1.04); cerebral palsy and other paralytic syndromes with a CSMF of 0.46% (95% CI: 0.27-0.65); and intrauterine hypoxia in neonates with a CSMF of 2.06% (95% CI: 1.12-3.01). Overall, mortality of ND was estimated with a CSMF of 4.99% (95% CI: 4.40-5.58).; Conclusions; : The SAVVY survey provides estimates of mortality burden of ND in Tanzania. The study provides a basis for monitoring trends of ND and contributes to advancing knowledge of the burden of diseases. Integrating morbidities measures into the SAVVY design will provide comprehensive measures of burden of ND taking into account lifetime disabilities created by ND

Health & Demographic Surveillance System Profile: The Rufiji Health and Demographic Surveillance System (Rufiji HDSS)

The Rufiji Health and Demographic Surveillance System (HDSS) was established in October 1998 to evaluate the impact on burden of disease of health system reforms based on locally generated data, prioritization, resource allocation and planning for essential health interventions. The Rufiji HDSS collects detailed information on health and survival and provides a framework for population-based health research of relevance to local and national health priorities. In December 2012 the population under surveillance was about 105 503 people, residing in 19 315 households. Monitoring of households and members within households is undertaken in regular 6-month cycles known as ‘rounds'. Self reported information is collected on demographic, household, socioeconomic and geographical characteristics. Verbal autopsy is conducted using standardized questionnaires, to determine probable causes of death. In conjunction with core HDSS activities, the ongoing studies in Rufiji HDSS focus on maternal and new-born health, evaluation of safety of artemether-lumefantrine (AL) exposure in early pregnancy and the clinical safety of a fixed dose of dihydroartemisinin-piperaquine (DHA-PQP) in the community. Findings of studies conducted in Rufiji HDSS can be accessed at www.ihi.or.tz/IHI-Digital-Librar

Trends in socioeconomic disparities in a rapid under-five mortality transition: a longitudinal study in United Republic of Tanzania

Abstract: Objective To explore trends in socioeconomic disparities and under-five mortality rates in rural parts of United Republic of Tanzania between 2000 and 2011. Methods: We used longitudinal data on births, deaths, migrations, maternal educational attainment and household characteristics from the Ifakara and Rufiji health and demographic surveillance systems. We estimated hazard ratios (HR) for associations between mortality and maternal educational attainment or relative household wealth, using Cox hazard regression models. Findings: The under-five mortality rate declined in Ifakara from 132.7 deaths per 1000 live births (95% confidence interval, CI: 119.3–147.4) in 2000 to 66.2 (95%CI: 59.0–74.3) in 2011 and in Rufiji from 118.4 deaths per 1000 live births (95% CI: 107.1– 130.7) in 2000 to 76.2 (95% CI: 66.7–86.9) in 2011. Combining both sites, in 2000– 2001, the risk of dying for children of uneducated mothers was 1.44 (95% CI: 1.08– 1.92) higher than for children of mothers who had received education beyond primary school. In 2010–2011, the HR was 1.18 (95% CI: 0.90–1.55). In contrast mortality disparities between richest and poorest quintiles worsened in Rufiji, from 1.20 (95% CI: 0.99–1.47) in 2000–2001 to 1.48 (95% CI: 1.15–1.89) in 2010–2011, while in Ifakara, disparities narrowed from 1.30 (95% CI: 1.09–1.55) to 1.15 (95% CI: 0.95–1.39) in the same period. Conclusion: While childhood survival has improved, mortality disparities still persist, suggesting a need for policies and programmes that both reduce child mortality and address socioeconomic disparities

Does Proximity to Health Facilities Improve Child Survival? New Evidence from a Longitudinal Study in Rural Tanzania

Distance to health facilities is often cited as a major barrier limiting access to care in sub-Saharan and other developing countries. There are however limited data on the causal effects of distance to facilities on child survival. Existing estimates may be biased because 1) most existing data are on distance to health care facilities are cross-sectional, and 2) existing analyses do not account for the endogeneity of residential choices and health services location. This paper uses unique longitudinal data collected in a rural district of Tanzania to test whether enhanced proximity to health services arising from investment in dispensaries contributed to the rapid decline in underfive mortality recently observed in Tanzania. Data on births, deaths, household socioeconomic characteristics and migrations have been recorded every 120 days since 1999 (n≈85,000). Geographic data on the precise location of households and health facilities have also been collected over time. We use multivariate analysis 1) to measure the causal effects of distance to health facilities on child survival and 2) to test for possible interactions between distance to health facilities and socioeconomic characteristics of households (e.g., educational attainment, wealth). Initial results indicate that, from 2000 to 2010, child mortality declined close to 40% (from 110 to 70 per 1000). The distance to the closest health facility remained a strong determinant of child survival, even after adjusting for endogeneity biases. The development of community-based primary health care in rural communities by posting community health assistants, and conducting regular household visits, can improve health outcomes. It can also increase equity by offsetting the detrimental effects of low maternal education, householdpoverty and distance to health facilities

Tanzania’s Countdown to 2015: an analysis of two decades of progress and gaps for reproductive, maternal, newborn, and child health, to inform priorities for post-2015

Background Tanzania is on track to meet Millennium Development Goal (MDG) 4 for child survival, but is making insuffi cient progress for newborn survival and maternal health (MDG 5) and family planning. To understand this mixed progress and to identify priorities for the post-2015 era, Tanzania was selected as a Countdown to 2015 case study. Methods We analysed progress made in Tanzania between 1990 and 2014 in maternal, newborn, and child mortality, and unmet need for family planning, in which we used a health systems evaluation framework to assess coverage and equity of interventions along the continuum of care, health systems, policies and investments, while also considering contextual change (eg, economic and educational). We had fi ve objectives, which assessed each level of the health systems evaluation framework. We used the Lives Saved Tool (LiST) and did multiple linear regression analyses to explain the reduction in child mortality in Tanzania. We analysed the reasons for the slower changes in maternal and newborn survival and family planning, to inform priorities to end preventable maternal, newborn, and child deaths by 2030. Findings In the past two decades, Tanzania’s population has doubled in size, necessitating a doubling of health and social services to maintain coverage. Total health-care fi nancing also doubled, with donor funding for child health and HIV/AIDS more than tripling. Trends along the continuum of care varied, with preventive child health services reaching high coverage (≥85%) and equity (socioeconomic status diff erence 13–14%), but lower coverage and wider inequities for child curative services (71% coverage, socioeconomic status diff erence 36%), facility delivery (52% coverage, socioeconomic status diff erence 56%), and family planning (46% coverage, socioeconomic status diff erence 22%). The LiST analysis suggested that around 39% of child mortality reduction was linked to increases in coverage of interventions, especially of immunisation and insecticide-treated bednets. Economic growth was also associated with reductions in child mortality. Child health programmes focused on selected high-impact interventions at lower levels of the health system (eg, the community and dispensary levels). Despite its high priority, implementation of maternal health care has been intermittent. Newborn survival has gained attention only since 2005, but high-impact interventions are already being implemented. Family planning had consistent policies but only recent reinvestment in implementation. Interpretation Mixed progress in reproductive, maternal, newborn, and child health in Tanzania indicates a complex interplay of political prioritisation, health fi nancing, and consistent implementation. Post-2015 priorities for Tanzania should focus on the unmet need for family planning, especially in the Western and Lake regions; addressing gaps for coverage and quality of care at birth, especially in rural areas; and continuation of progress for child health

Tanzania's countdown to 2015: an analysis of two decades of progress and gaps for reproductive, maternal, newborn, and child health, to inform priorities for post-2015.

BACKGROUND: Tanzania is on track to meet Millennium Development Goal (MDG) 4 for child survival, but is making insufficient progress for newborn survival and maternal health (MDG 5) and family planning. To understand this mixed progress and to identify priorities for the post-2015 era, Tanzania was selected as a Countdown to 2015 case study. METHODS: We analysed progress made in Tanzania between 1990 and 2014 in maternal, newborn, and child mortality, and unmet need for family planning, in which we used a health systems evaluation framework to assess coverage and equity of interventions along the continuum of care, health systems, policies and investments, while also considering contextual change (eg, economic and educational). We had five objectives, which assessed each level of the health systems evaluation framework. We used the Lives Saved Tool (LiST) and did multiple linear regression analyses to explain the reduction in child mortality in Tanzania. We analysed the reasons for the slower changes in maternal and newborn survival and family planning, to inform priorities to end preventable maternal, newborn, and child deaths by 2030. FINDINGS: In the past two decades, Tanzania's population has doubled in size, necessitating a doubling of health and social services to maintain coverage. Total health-care financing also doubled, with donor funding for child health and HIV/AIDS more than tripling. Trends along the continuum of care varied, with preventive child health services reaching high coverage (≥85%) and equity (socioeconomic status difference 13-14%), but lower coverage and wider inequities for child curative services (71% coverage, socioeconomic status difference 36%), facility delivery (52% coverage, socioeconomic status difference 56%), and family planning (46% coverage, socioeconomic status difference 22%). The LiST analysis suggested that around 39% of child mortality reduction was linked to increases in coverage of interventions, especially of immunisation and insecticide-treated bednets. Economic growth was also associated with reductions in child mortality. Child health programmes focused on selected high-impact interventions at lower levels of the health system (eg, the community and dispensary levels). Despite its high priority, implementation of maternal health care has been intermittent. Newborn survival has gained attention only since 2005, but high-impact interventions are already being implemented. Family planning had consistent policies but only recent reinvestment in implementation. INTERPRETATION: Mixed progress in reproductive, maternal, newborn, and child health in Tanzania indicates a complex interplay of political prioritisation, health financing, and consistent implementation. Post-2015 priorities for Tanzania should focus on the unmet need for family planning, especially in the Western and Lake regions; addressing gaps for coverage and quality of care at birth, especially in rural areas; and continuation of progress for child health. FUNDING: Government of Canada, Foreign Affairs, Trade, and Development; US Fund for UNICEF; and the Bill & Melinda Gates Foundation