Burden Of Disease In Low- And Middle-income Countries Research Articles

Pharmacovigilance in Pregnancy Studies, Exposures and Outcomes Ascertainment, and Findings from Low- and Middle-Income Countries: A Scoping Review.

Pharmacovigilance (PV), or the ongoing safety monitoring after a medication has been licensed, plays a crucial role in pregnancy, as clinical trials often exclude pregnant people. It is important to understand how pregnancy PV projects operate in low- and middle-income countries (LMICs), where there is a disproportionate lack of PV data yet ahigh burden of adverse pregnancy outcomes. We conducted a scoping review to assess how exposures and outcomes were measured in recently published pregnancy PV projects in LMICs. We utilized a search string, secondary review, and team knowledge to review publications focusing on therapeutic or vaccine exposures among pregnant people in LMICs. We screened abstracts for relevance before conducting a full text review, and documented measurements of exposures and outcomes (categorized as maternal, birth, or neonatal/infant) among other factors, including study topic, setting, and design, comparator groups, and funding sources. We identified 31 PV publications spanning at least 24 LMICs, all focusing on therapeutics or vaccines for infectious diseases, including HIV (n = 17), tuberculosis (TB; n = 9), malaria (n = 7), pertussis, tetanus, and diphtheria (n = 1), and influenza (n = 3). As for outcomes, n = 15, n = 31, and n = 20 of the publications covered maternal, birth, and neonatal/infant outcomes, respectively. Among HIV-specific publications, the primary exposure-outcome relationship of focus was exposure to maternal antiretroviral therapy and adverse outcomes. For TB-specific publications, the main exposures of interest were second-line drug-resistant TB and isoniazid-based prevention therapeutics for pregnant people living with HIV. For malaria-specific publications, the primary exposure-outcome relationship of interest was antimalarial medication exposure during pregnancy and adverse outcomes. Among vaccine-focused publications, the exposure was assessed during a specific time during pregnancy, with an overall interest in vaccine safety and/or efficacy. The study settings were frequently from Africa, designs varied from cohort or cross-sectional studies to clinical trials, and funding sources were largely from high-income countries. The published pregnancy PV projects were largely centered in Africa and concerned with infectious diseases. This may reflect the disease burden in LMICs but also funding priorities from high-income countries. As the prevalence of non-communicable diseases increases in LMICs, PV projects will have to broaden their scope. Birth and neonatal/infant outcomes were most reported, with fewer reporting on maternal outcomes and none on longer-term child outcomes; additionally, heterogeneity existed in definitions and ascertainment of specific measures. Notably, almost all projects covered a single therapeutic exposure, missing an opportunity to leverage their projects to cover additional exposures, add scientific rigor, create uniformity across health services, and bolster existing health systems. For many publications, the timing of exposure, specifically by trimester, was crucial to maternal and neonatal safety. While currently published pregnancy PV literature offer insights into the PV landscape in LMICs, further work is needed to standardize definitions and measurements, integrate PV projects across health services, and establish longer-term monitoring.

P13.01.A Challenges and Solutions for Establishing a CNS Tumor Registry in Africa

Abstract Background CNS tumor registries (CTR) has evolved to a key tool for data collection, evaluation of diagnostic and treatment of patients suffering from tumors of the central nervous system (tCNS) in the U.S, but CTR in Africa does not yet exist. In comparison to high-income countries (HIC), many low- and middle-income countries (LMIC) do not yet have national or central CNS tumor registries. Furthermore, appropriate diagnostic steps like MRI and pathological analysis are still scarce in many LMIC. Improving the availability of CTR in resource- limited regions could allow better understanding of some specificities of tCNS including incidence, prevalence, mortality and morbidity. However, CTR, MRI and pathological analysis tend to be costly and thus difficult to implement in the LMIC setting. Material and Methods A review of the current body of literature on tCNS in Africa was conducted using multiple scientific online data bases. Search terms included ,,CNS tumor registry,” “developing countries,” “low and middle income,” and other related terms as starting point for future initiatives. Results It was found that more than 1,3 billion people residing in Africa lack access to a continental CTR. There is no well established standards for reporting tCNS. Most tCNS are still underreported in many countries of Africa. The exact burden of tCNS in Africa is unknown. Although many successful, long-term, initiatives for international neurological and neurosurgical collaborations are published, any CTR of Africa similarly to the Central Brain Tumor Registry of the United States (CBTRUS) is lacking. Conclusion: Disparities in access to care for patients suffering from tCNS have been well published but well established solutions are still under investigations. Partnerships between centers in LMIC and HIC are making progress to better understand the burden of disease in LMIC and to create context-specific solutions for practice in the LMIC setting. Collaboration between the World Health Organisation, national centers for disease control in Africa, departments of neuroscience in LMIC and well established registries like the CBTRUS as well as other interested groups could be meaningful strategical steps to be initiated for the establishment of CTR in Africa. A CTR for Africa could lead to better comprehension of tCNS in Africa, thus facilitate prevention, diagnostic, treatment and research.

Implementing a Neurotrauma Registry in Latin America and the Caribbean.

Background Traumatic brain injury (TBI) has a disproportionately greater impact in low- and middle-income countries (LMICs). One strategy to reduce the burden of disease in LMICs is through the implementation of a trauma registry that standardizes the assessment of each patient's management of care. Objective This study aims to ascertain the interest of Latin America and the Caribbean (LAC) nations in establishing a shared neurotrauma registry in the regional block, based on an existing framework for collaboration. Methods A descriptive review was performed regarding the interests of LAC nations in implementing a shared neurotrauma registry in their region. We convened a meeting with seven Caribbean and five Latin American nations. Results One hundred percent ( n = 12) of the LAC representatives including neurosurgeons, neurointensivists, ministers of health, and chief medical officers/emergency medical technicians (EMTs) agreed to adopt the registry for tracking the burden of TBI and associated pathologies within the region. Conclusion The implementation of a neurotrauma registry can benefit the region through a shared database to track disease, improve outcomes, build research, and ultimately influence policy.

A Socio-Ecological Framework for Cancer Prevention in Low and Middle-Income Countries.

Cancer incidence and mortality rates continue to rise globally, a trend mostly driven by preventable cancers occurring in low-and middle-income countries (LMICs). There is growing concern that many LMICs are ill-equipped to cope with markedly increased burden of cancer due to lack of comprehensive cancer control programs that incorporate primary, secondary, and tertiary prevention strategies. Notably, few countries have allocated budgets to implement such programs. In this review, we utilize a socio-ecological framework to summarize primary (risk reduction), secondary (early detection), and tertiary (treatment and survivorship) strategies to reduce the cancer burden in these countries across the individual, organizational, community, and policy levels. We highlight strategies that center on promoting health behaviors and reducing cancer risk, including diet, tobacco, alcohol, and vaccine uptake, approaches to promote routine cancer screenings, and policies to support comprehensive cancer treatment. Consistent with goals promulgated by the United Nations General Assembly on Noncommunicable Disease Prevention and Control, our review supports the development and implementation of sustainable national comprehensive cancer control plans in partnership with local communities to enhance cultural relevance and adoption, incorporating strategies across the socio-ecological framework. Such a concerted commitment will be necessary to curtail the rising cancer and chronic disease burden in LMICs.

Associations of Growth Impairment and Body Composition among South African School-Aged Children Enrolled in the KaziAfya Project.

(1) Background: Early childhood malnutrition may result in increased fat mass (FM) among school-aged children in low- and middle-income countries (LMICs). We explored whether South African children with shorter stature have greater overall and abdominal FM compared to normal stature children. (2) Methods: Baseline assessments of body composition and weight were determined among school-aged children enrolled in a randomized controlled trial in Port Elizabeth, South Africa, using bioelectrical impedance analysis. Multiple linear regression models tested associations of children’s height and degree of stunting with FM, fat free mass (FFM), truncal fat mass (TrFM), and truncal fat free mass (TrFFM) overall and by sex. (3) Results: A total of 1287 children (619 girls, 668 boys) were assessed at baseline. Reduced child height was associated with higher FM and lower FFM and TrFFM, but these associations were reversed with increases in height. Girls classified as mildly or moderately/severely stunted had higher FM and TrFM but lower FFM and TrFFM, while no association was found for boys. (4) Conclusions: Our study suggests that efforts to reduce the non-communicable disease burden in LMICs should target growth-impaired children who may have greater overall FM and greater abdominal FM.

The Health & Economic Disparities of Congenital Musculoskeletal Disease Worldwide: An Analysis of 25 Years (1992-2017).

Background: Large disparities exist in congenital musculoskeletal disease burden worldwide. The purpose of this study is to examine and quantify the health and economic disparities of congenital musculoskeletal disease by country income level from 1992 to 2017. Methods: The Global Burden of Disease database was queried for information on disease burden attributed to “congenital musculoskeletal and limb anomalies” from 1992 to 2017. Gross national income per capita was extracted from the World Bank website. Nonparametric Kruskal–Wallis tests were used to compare morbidity and mortality across years and income levels. The number of avertable DALYs was converted to an economic disparity using the human-capital and value of a statistical life approach. Results: From 1992 to 2017, a significant decrease in deaths/100 000 was observed only in upper-middle and high income countries. Northern Africa, the Middle East, and Eastern Europe were disproportionately affected. If the burden of disease in low- and middle- income countries (LMICs) was equivalent to that in high income countries (HICs), 10% of all DALYs and 70% of all deaths attributable to congenital musculoskeletal disease in LMICs could be averted. This equates to an economic disparity of about $2 billion to $3 billion (in 2020 $USD). Conclusion: Considerable inequity exists in the burden of congenital musculoskeletal disease worldwide and there has been no change over the last 25 years in total disease burden and geographical distribution. By reducing the disease burden in LMICs to rates found in HICs, a large proportion of the health and economic consequences could be averted.

Workforce Cost Model for Expanding Congenital and Rheumatic Heart Disease Services in Kenya.

Cardiovascular disease is the number one global killer, with over three quarters of these deaths arising from the populations of low- and middle-income countries (LMICs). Addressing the burden of cardiovascular disease in LMICs must include medical and surgical services for these patients. In this article, we model the needs and costs to scale up the cardiac provider workforce in Kenya, which can be adapted to other LMICs based on country-specific workforce hours and workforce salaries. Using published epidemiological reports from sub-Saharan Africa, we structured the model based on the expected disease burden of congenital and rheumatic disease in a simulated 1,000-person population. Services modeled include clinic visits, echocardiograms, diagnostic cardiac catheterizations, interventional catheterizations, and heart surgery. Costs were modeled based on Kenyan public sector salaries. After scaling the model, we created a sensitivity analysis of change in service duration and salaries. Based on a 1,000-person Kenyan population, we estimate that 2.5 heart surgeries will be needed every year, with a corresponding annual workforce cost of US$526. Including accompanying services of clinic visits, echocardiograms, and both diagnostic and interventional cardiac catheterizations, the total annual workforce cost is US$899. Based on estimated productive hours for public sector workforce, 196 full-time equivalent cardiac surgeons will be needed for the entire population of Kenya (2017 figure). We present a model for appropriate cardiovascular service staffing based on disease burden and workforce costs. This model can be scaled up as needed to plan for local capacity building.

Prevalence of angina and co-morbid conditions among older adults in six low- and middle-income countries: Evidence from SAGE Wave 1

BackgroundGlobal commitments to reduce cardiovascular disease (CVD) burden by 2025 will require data on CVDs from lower income countries. This study aimed to estimate the prevalence of angina, and its association with hypertension, diabetes, and depression, in six low- and middle-income countries (LMICs). MethodsData from the World Health Organization (WHO) Study on global AGEing and adult health (SAGE) Wave 1 from China, Ghana, India, Mexico, Russia and South Africa were utilized. Multivariable logistic regression methods were used to examine the factors associated with angina. ResultsA total of 31,443 respondents aged 50 years and over were included in these analyses. The prevalence of angina was highest in Russia (39%), lowest in China (8%), and consistently higher in women than men. Angina was comorbid with chronic conditions and depression but patterns varied across countries. Depression was negatively associated with angina among older adults in Ghana but was positively associated with angina in all other countries. Hypertension was associated with increased odds of angina among older adults in China (OR 1.9; 95% CI 1.59–2.25), India (OR 1.4; 95% CI 1.14–1.78) and Russia (OR 3.7; 95% CI 2.33–6.00). Diabetes was associated with higher odds of angina in China (OR 1.6; 95% CI 1.15–2.15), Russia (OR 2.5; 95% CI 1.57–3.87), and South Africa (OR 4.1; 95% CI 2.49–6.88). ConclusionsCVD is a significant contributor to disease burden in LMICs. Angina was often co-morbid with other conditions, therefore compelling health systems to develop longer-term integrated care systems to address co- and multi-morbidity.

Global Disparities Between Pediatric Publications and Disease Burden From 2006 to 2015.

There is a disproportionate burden of pediatric disease in low- and middle-income countries (LMICs); however, the proportion and relation of published articles to childhood disease burden in LMICs have not been assessed previously. This study aimed to determine whether published articles and disease topics from research conducted in LMICs in the most widely cited pediatric journals reflected the global burden of childhood disease. We reviewed all articles published from 2006 to 2015 in the 3 pediatric journals with the highest Eigenfactor scores to identify studies conducted in the World Bank–designated LMICs. We abstracted study topic, design, purpose, country, and funding sources. We derived descriptive statistics, Fisher’s exact χ2 test, Monte Carlo estimates, and Spearman’s rank order coefficients. Of the 19 676 articles reviewed, 10 494 were original research articles. Of those, 965 (9.2%) were conducted in LMICs. Over the study period, the proportion of published articles originating from LMICs increased (r2 = 0.77). Disease topics did not reflect the underlying burden of disease as measured in disability-adjusted life years (Spearman’s rank order coefficient = 0.25). Despite bearing the majority of the world’s burden of disease, articles from LMICs made up a small proportion of all published articles in the 3 pediatric journals with the highest Eigenfactor scores. The number of published articles from LMICs increased over the study period; nevertheless, the topics did not coincide with the burden of disease in LMICs. These discrepancies highlight the need for development of a research agenda to address the diseases that are the greatest threat to the majority of children worldwide.

Introduction: Implementation Science to Reduce Household Air Pollution (HAP) Exposures in Low and Middle-Income Countries (LMICs)

HAP exposures are responsible for a major proportion of the total disease burden in LMICs. To address this, the NIH led Clean Cooking Implementation Science Network (ISN) is developing methods to elucidate technologies, conditions, and implementation strategies that can result in the largest reductions in HAP exposures. The challenge is to accelerate widespread, sustained and nearly exclusive adoption of clean cooking to promote public health. In this symposium we present a brief introduction to the network and its approach, followed by study results from interventional and natural experiments in India and Sub-Saharan Africa. For example, India has recently launched an enormous effort to provide access to clean cooking fuels such as Liquified Petroleum Gas (LPG) to nearly 50 million homes by 2019, but challenges of sustaining LPG use remain to be overcome. Implementation science has evolved precisely to meet this kind of complex, multidimensional problem. Finance, access to services, ambient air quality, climate, home construction, community structure, cultural traditions and gender are among the complex variables addressed in the network’s research. The ISN projects presented here use a diversity of methods – including social network analysis, microfinance experimentation, novel survey methodologies and sensor-based monitoring of stove-use and resulting exposure levels – to understand the potential drivers of decision making in rural and peri-urban, low income settings. In this brief introduction to the research we provide background on the scope of the problem and an outline of the approaches we are taking to employ research that will accelerate the transition to clean cooking fuels around the world.

Challenges and Solutions for Functional Neurosurgery in Developing Countries.

Functional neurosurgery techniques remain integral to the neurosurgical treatment armamentarium but data on global implementation remains scarce. In comparison to high-income countries (HIC), low- and middle-income countries (LMIC) suffer from an increased prevalence of diseases like epilepsy, which may be amenable to functional techniques, and therefore, LMIC may benefit from an increased utilization of these treatment modalities. However, functional techniques tend to be expensive and thus difficult to implement in the LMIC setting. A review was performed to assess the current status of functional neurosurgical techniques in LMIC as a starting point for future initiatives.For methodology, a review of the current body of literature on functional neurosurgery in LMIC was conducted through the United States National Library of Medicine Pubmed search engine. Search terms included “functional neurosurgery,” “developing countries,” “low and middle income,” and other related terms.It was found that though five billion people lack access to safe surgical care, the burden of disease amenable to treatment with functional neurosurgical procedures remains unknown. Increasingly, reports of successful, long-term, international neurosurgical collaborations are being reported, but reports in the sub-field of functional neurosurgery are lacking.In conclusion, awareness of global surgical disparities has increased dramatically while global guidelines for functional techniques are currently lacking. A concerted effort can harness these techniques for wider practice. Partnerships between centers in LMIC and HIC are making progress to better understand the burden of disease in LMIC and to create context-specific solutions for practice in the LMIC setting, but more collaborations are warranted.

Burden of disease from toxic waste sites in India, Indonesia, and the Philippines in 2010.

Background: Prior calculations of the burden of disease from toxic exposures have not included estimates of the burden from toxic waste sites due to the absence of exposure data.Objective: We developed a disability-adjusted life year (DALY)-based estimate of the disease burden attributable to toxic waste sites. We focused on three low- and middle-income countries (LMICs): India, Indonesia, and the Philippines.Methods: Sites were identified through the Blacksmith Institute’s Toxic Sites Identification Program, a global effort to identify waste sites in LMICs. At least one of eight toxic chemicals was sampled in environmental media at each site, and the population at risk estimated. By combining estimates of disease incidence from these exposures with population data, we calculated the DALYs attributable to exposures at each site.Results: We estimated that in 2010, 8,629,750 persons were at risk of exposure to industrial pollutants at 373 toxic waste sites in the three countries, and that these exposures resulted in 828,722 DALYs, with a range of 814,934–1,557,121 DALYs, depending on the weighting factor used. This disease burden is comparable to estimated burdens for outdoor air pollution (1,448,612 DALYs) and malaria (725,000 DALYs) in these countries. Lead and hexavalent chromium collectively accounted for 99.2% of the total DALYs for the chemicals evaluated.Conclusions: Toxic waste sites are responsible for a significant burden of disease in LMICs. Although some factors, such as unidentified and unscreened sites, may cause our estimate to be an underestimate of the actual burden of disease, other factors, such as extrapolation of environmental sampling to the entire exposed population, may result in an overestimate of the burden of disease attributable to these sites. Toxic waste sites are a major, and heretofore underrecognized, global health problem.

Developing sub-acute, non-acute and special groups in the universal grouper

The use of Casemix system as providers’ reimbursement method under social health insurance schemes has spread beyond high-income countries. Over the last decade many low and middle-income countries (LMIC) have started to implement Casemix system to replace the conventional yet inefficient fee-for-service as provider payment mechanism. UNU-IIGH launched an international grouper called UNU-CBG in 2010 to support the implementation of Casemix system in LMIC. To date, UNU-CBG has been introduced in 12 countries in different phases of implementation process. UNU-CBG was designed to function as an international grouper that can be customized and adapted to suit the local needs and norms of each country. However inability to provide robust groupings for sub-acute and chronic conditions is a major limitation in the use of Casemix system in these countries. Sub-acute and chronic diseases that account for more than two thirds of disease burden in LMIC should be categorized in mutually exclusive groups if the reimbursement were to be made using Casemix system. Researchers in UNU-IIGH and International Casemix and Clinical Coding Centre of UKM have been working very hard for the past two years to upgrade the capacity of UNU-CBG grouper to classify sub-acute and chronic cases into Casemix group. Additional variables included in the new grouping algorithm are extended length of stay, costly prostheses, drugs, procedures, investigations and scores of Activity of Daily Living. The new version of UNU-CBG launched during this conference provides an opportunity for social health insurance managers in LMIC to use Casemix system as a total solution for provider payment method.

Mental health in low- and middle-income countries

Mental disorders in low- and middle-income countries (LAMIC) do not attract global health policy attention. This article is based on a selective review of research on mental disorders in adults in LAMIC since 2001 and recent analyses of disease burden in developing countries. Mental disorders account for 11.1% of the total burden of disease in LAMIC. Unipolar depressive disorder is the single leading neuropsychiatric cause of disease burden. Alcohol use disorders account for nearly 4% of the attributable disease burden in LAMIC. Mental disorders are closely associated with other public health concerns such as maternal and child health and HIV/AIDS. Poverty, low education, social exclusion, gender disadvantage, conflict and disasters are the major social determinants of mental disorders. Clinical trials demonstrate that locally available, affordable interventions in community and primary care settings are effective for the management of mental disorders. Mental health resources are very scarce and investment in mental health is < 1% of the health budget in many countries. The majority of people with mental disorders do not receive evidence-based care, leading to chronicity, suffering and increased costs of care. Strengthening care and services for people with mental disorders is a priority; this will need additional investment in human resources and piggy backing on existing public health programmes. Campaigns to increase mental health literacy are needed at all levels of the health system.