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1.  Burden of Depressive Disorders by Country, Sex, Age, and Year: Findings from the Global Burden of Disease Study 2010 
PLoS Medicine  2013;10(11):e1001547.
In this paper, Ferrari and colleagues analyzed the burden of depressive disorders in GBD 2010 and identified depressive disorders as a leading cause of burden. The authors present severity proportions; burden by country, region, age, sex, and year; as well as burden of depressive disorders as a risk factor for suicide and ischemic heart disease.
Please see later in the article for the Editors' Summary
Background
Depressive disorders were a leading cause of burden in the Global Burden of Disease (GBD) 1990 and 2000 studies. Here, we analyze the burden of depressive disorders in GBD 2010 and present severity proportions, burden by country, region, age, sex, and year, as well as burden of depressive disorders as a risk factor for suicide and ischemic heart disease.
Methods and Findings
Burden was calculated for major depressive disorder (MDD) and dysthymia. A systematic review of epidemiological data was conducted. The data were pooled using a Bayesian meta-regression. Disability weights from population survey data quantified the severity of health loss from depressive disorders. These weights were used to calculate years lived with disability (YLDs) and disability adjusted life years (DALYs). Separate DALYs were estimated for suicide and ischemic heart disease attributable to depressive disorders.
Depressive disorders were the second leading cause of YLDs in 2010. MDD accounted for 8.2% (5.9%–10.8%) of global YLDs and dysthymia for 1.4% (0.9%–2.0%). Depressive disorders were a leading cause of DALYs even though no mortality was attributed to them as the underlying cause. MDD accounted for 2.5% (1.9%–3.2%) of global DALYs and dysthymia for 0.5% (0.3%–0.6%). There was more regional variation in burden for MDD than for dysthymia; with higher estimates in females, and adults of working age. Whilst burden increased by 37.5% between 1990 and 2010, this was due to population growth and ageing. MDD explained 16 million suicide DALYs and almost 4 million ischemic heart disease DALYs. This attributable burden would increase the overall burden of depressive disorders from 3.0% (2.2%–3.8%) to 3.8% (3.0%–4.7%) of global DALYs.
Conclusions
GBD 2010 identified depressive disorders as a leading cause of burden. MDD was also a contributor of burden allocated to suicide and ischemic heart disease. These findings emphasize the importance of including depressive disorders as a public-health priority and implementing cost-effective interventions to reduce its burden.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Depressive disorders are common mental disorders that occur in people of all ages across all world regions. Depression—an overwhelming feeling of sadness and hopelessness that can last for months or years—can make people feel that life is no longer worth living. People affected by depression lose interest in the activities they used to enjoy and can also be affected by physical symptoms such as disturbed sleep. Major depressive disorder (MDD, also known as clinical depression) is an episodic disorder with a chronic (long-term) outcome and increased risk of death. It involves at least one major depressive episode in which the affected individual experiences a depressed mood almost all day, every day for at least 2 weeks. Dysthymia is a milder, chronic form of depression that lasts for at least 2 years. People with dysthymia are often described as constantly unhappy. Both these subtypes of depression (and others such as that experienced in bipolar disorder) can be treated with antidepressant drugs and with talking therapies.
Why Was This Study Done?
Depressive disorders were a leading cause of disease burden in the 1990 and 2000 Global Burden of Disease (GBD) studies, collaborative scientific efforts that quantify the health loss attributable to diseases and injuries in terms of disability adjusted life years (DALYs; one DALY represents the loss of a healthy year of life). DALYs are calculated by adding together the years of life lived with a disability (YLD, a measure that includes a disability weight factor reflecting disease severity) and the years of life lost because of disorder-specific premature death. The GBD initiative aims to provide data that can be used to improve public-health policy. Thus, knowing that depressive disorders are a leading cause of disease burden worldwide has helped to prioritize depressive disorders in global public-health agendas. Here, the researchers analyze the burden of MDD and dysthymia in GBD 2010 by country, region, age, and sex, and calculate the burden of suicide and ischemic heart disease attributable to depressive disorders (depression is a risk factor for suicide and ischemic heart disease). GBD 2010 is broader in scope than previous GBD studies and quantifies the direct burden of 291 diseases and injuries and the burden attributable to 67 risk factors across 187 countries.
What Did the Researchers Do and Find?
The researchers collected data on the prevalence, incidence, remission rates, and duration of MDD and dysthymia and on the excess deaths caused by these disorders from published articles. They pooled these data using a statistical method called Bayesian meta-regression and calculated YLDs for MDD and dysthymia using disability weights collected in population surveys. MDD accounted for 8.2% of global YLDs in 2010, making it the second leading cause of YLDs. Dysthymia accounted for 1.4% of global YLDs. MDD and dysthymia were also leading causes of DALYs, accounting for 2.5% and 0.5% of global DALYs, respectively. The regional variation in the burden was greater for MDD than for dysthymia, the burden of depressive disorders was higher in women than men, the largest proportion of YLDs from depressive disorders occurred among adults of working age, and the global burden of depressive disorders increased by 37.5% between 1990 and 2010 because of population growth and ageing. Finally, MDD explained an additional 16 million DALYs and 4 million DALYs when it was considered as a risk factor for suicide and ischemic heart disease, respectively. This “attributable” burden increased the overall burden of depressive disorders to 3.8% of global DALYs.
What Do These Findings Mean?
These findings update and extend the information available from GBD 1990 and 2000 on the global burden of depressive disorders. They confirm that depressive disorders are a leading direct cause of the global disease burden and show that MDD also contributes to the burden allocated to suicide and ischemic heart disease. The estimates of the global burden of depressive disorders reported in GBD 2010 are likely to be more accurate than those in previous GBD studies but are limited by factors such as the sparseness of data on depressive disorders from developing countries and the validity of the disability weights used to calculate YLDs. Even so, these findings reinforce the importance of treating depressive disorders as a public-health priority and of implementing cost-effective interventions to reduce their ubiquitous burden.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001547.
The US National Institute of Mental Health provides information on all aspects of depression
The UK National Health Service Choices website also provides detailed information about depression and includes personal stories about depression
More personal stories about depression are available from healthtalkonline.org
MedlinePlus provides links to other resources about depression (in English and Spanish)
The World Health Organization provides information on depression and on the global burden of disease (in several languages)
Information about the Global Burden of Disease initiative is available
beyondblue provides many resources on depression
The Queensland Centre for Mental Health Research provides information on epidemiology and the global burden of disease specifically for mental disorders
doi:10.1371/journal.pmed.1001547
PMCID: PMC3818162  PMID: 24223526
2.  The Burden of Parasitic Zoonoses in Nepal: A Systematic Review 
Background
Parasitic zoonoses (PZs) pose a significant but often neglected threat to public health, especially in developing countries. In order to obtain a better understanding of their health impact, summary measures of population health may be calculated, such as the Disability-Adjusted Life Year (DALY). However, the data required to calculate such measures are often not readily available for these diseases, which may lead to a vicious circle of under-recognition and under-funding.
Methodology
We examined the burden of PZs in Nepal through a systematic review of online and offline data sources. PZs were classified qualitatively according to endemicity, and where possible a quantitative burden assessment was conducted in terms of the annual number of incident cases, deaths and DALYs.
Principal Findings
Between 2000 and 2012, the highest annual burden was imposed by neurocysticercosis and congenital toxoplasmosis (14,268 DALYs [95% Credibility Interval (CrI): 5450–27,694] and 9255 DALYs [95% CrI: 6135–13,292], respectively), followed by cystic echinococcosis (251 DALYs [95% CrI: 105–458]). Nepal is probably endemic for trichinellosis, toxocarosis, diphyllobothriosis, foodborne trematodosis, taeniosis, and zoonotic intestinal helminthic and protozoal infections, but insufficient data were available to quantify their health impact. Sporadic cases of alveolar echinococcosis, angiostrongylosis, capillariosis, dirofilariosis, gnathostomosis, sparganosis and cutaneous leishmaniosis may occur.
Conclusions/Significance
In settings with limited surveillance capacity, it is possible to quantify the health impact of PZs and other neglected diseases, thereby interrupting the vicious circle of neglect. In Nepal, we found that several PZs are endemic and are imposing a significant burden to public health, higher than that of malaria, and comparable to that of HIV/AIDS. However, several critical data gaps remain. Enhanced surveillance for the endemic PZs identified in this study would enable additional burden estimates, and a more complete picture of the impact of these diseases.
Author Summary
Various parasites that infect humans require animals in some stage of their life cycle. Infection with these so-called zoonotic parasites may vary from asymptomatic carriership to long-term morbidity and even death. Although data are still scarce, it is clear that parasitic zoonoses (PZs) present a significant burden for public health, particularly in poor and marginalized communities. So far, however, there has been relatively little attention to this group of diseases, causing various PZs to be labeled neglected tropical diseases. In this study, the authors reviewed a large variety of data sources to study the relevance and importance of PZs in Nepal. It was found that a large number of PZs are present in Nepal and are imposing an impact higher than that of malaria and comparable to that of HIV/AIDS. These results therefore suggest that PZs deserve greater attention and more intensive surveillance. Furthermore, this study has shown that even in settings with limited surveillance capacity, it is possible to quantify the impact of neglected diseases and, consequently, to break the vicious circle of neglect.
doi:10.1371/journal.pntd.0002634
PMCID: PMC3879239  PMID: 24392178
3.  Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990–2010: findings from the Global Burden of Disease Study 2010 
The Lancet. Global health  2013;1(5):e259-e281.
Summary
Background
The burden of ischaemic and haemorrhagic stroke varies between regions and over time. With differences in prognosis, prevalence of risk factors, and treatment strategies, knowledge of stroke pathological type is important for targeted region-specific health-care planning for stroke and could inform priorities for type-specific prevention strategies. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990–2010.
Methods
We searched Medline, Embase, LILACS, Scopus, PubMed, Science Direct, Global Health Database, the WHO library, and regional databases from 1990 to 2012 to identify relevant studies published between 1990 and 2010. We applied the GBD 2010 analytical technique (DisMod-MR) to calculate regional and country-specific estimates for ischaemic and haemorrhagic stroke incidence, mortality, mortality-to-incidence ratio, and disability-adjusted life-years (DALYs) lost, by age group (aged <75 years, ≥75 years, and in total) and country income level (high-income and low-income and middle-income) for 1990, 2005, and 2010.
Findings
We included 119 studies (58 from high-income countries and 61 from low-income and middle-income countries). Worldwide, the burden of ischaemic and haemorrhagic stroke increased significantly between 1990 and 2010 in terms of the absolute number of people with incident ischaemic and haemorrhagic stroke (37% and 47% increase, respectively), number of deaths (21% and 20% increase), and DALYs lost (18% and 14% increase). In the past two decades in high-income countries, incidence of ischaemic stroke reduced significantly by 13% (95% CI 6–18), mortality by 37% (19–39), DALYs lost by 34% (16–36), and mortality-to-incidence ratios by 21% (10–27). For haemorrhagic stroke, incidence reduced significantly by 19% (1–15), mortality by 38% (32–43), DALYs lost by 39% (32–44), and mortality-to-incidence ratios by 27% (19–35). By contrast, in low-income and middle-income countries, we noted a significant increase of 22% (5–30) in incidence of haemorrhagic stroke and a 6% (–7 to 18) non-significant increase in the incidence of ischaemic stroke. Mortality rates for ischaemic stroke fell by 14% (9–19), DALYs lost by 17% (–11 to 21%), and mortality-to-incidence ratios by 16% (–12 to 22). For haemorrhagic stroke in low-income and middle-income countries, mortality rates reduced by 23% (–18 to 25%), DALYs lost by 25% (–21 to 28), and mortality-to-incidence ratios by 36% (–34 to 28).
Interpretation
Although age-standardised mortality rates for ischaemic and haemorrhagic stroke have decreased in the past two decades, the absolute number of people who have these stroke types annually, and the number with related deaths and DALYs lost, is increasing, with most of the burden in low-income and middle-income countries. Further study is needed in these countries to identify which subgroups of the population are at greatest risk and who could be targeted for preventive efforts.
doi:10.1016/S2214-109X(13)70089-5
PMCID: PMC4181351  PMID: 25104492
4.  The Disease Burden of Taenia solium Cysticercosis in Cameroon 
Background
Taenia solium cysticercosis is an important zoonosis in many developing countries. Human neurocysticercosis is recognised as an important cause of epilepsy in regions where the parasite occurs. However, it is largely underreported and there is a lack of data about the disease burden. Because a body of information on human and porcine cysticercosis in Cameroon is becoming available, the present study was undertaken to calculate the impact of this neglected zoonosis.
Methods
Both the cost and Disability Adjusted Life Year (DALY) estimations were applied. All necessary parameters were collected and imported in R software. Different distributions were used according to the type of information available for each of the parameters.
Findings
Based on a prevalence of epilepsy of 3.6%, the number of people with neurocysticercosis-associated epilepsy was estimated at 50,326 (95% CR 37,299–65,924), representing 1.0% of the local population, whereas the number of pigs diagnosed with cysticercosis was estimated at 15,961 (95% CR 12,320–20,044), which corresponds to 5.6% of the local pig population. The total annual costs due to T. solium cysticercosis in West Cameroon were estimated at 10,255,202 Euro (95% CR 6,889,048–14,754,044), of which 4.7% were due to losses in pig husbandry and 95.3% to direct and indirect losses caused by human cysticercosis. The monetary burden per case of cysticercosis amounts to 194 Euro (95% CR 147–253). The average number of DALYs lost was 9.0 per thousand persons per year (95% CR 2.8–20.4).
Interpretation
This study provides an estimation of the costs due to T. solium cysticercosis using country-specific parameters and including the human as well as the animal burden of the zoonotic disease. A comparison with a study in South Africa indicates that the cost of inactivity, influenced by salaries, plays a predominant role in the monetary burden of T. solium cysticercosis. Therefore, knowing the salary levels and the prevalence of the disease might allow a rapid indication of the total cost of T. solium cysticercosis in a country. Ascertaining this finding with additional studies in cysticercosis-endemic countries could eventually allow the estimation of the global disease burden of cysticercosis. The estimated number of DALYs lost due to the disease was higher than estimates already available for some other neglected tropical diseases. The total estimated cost and number of DALYs lost probably underestimate the real values because the estimations have been based on epilepsy as the only symptom of cysticercosis.
Author Summary
Taenia solium cysticercosis is a zoonotic disease occurring in many developing countries. A relatively high prevalence in humans and pigs has been reported in several parts of the world, but insufficient data are available on the disease burden. Disease impact assessment needs detailed information on well-defined epidemiological and economic parameters. Our work conducted in West Cameroon over several years allowed us to collect the necessary information to estimate the impact of the parasite on the human and animal populations in this area using both cost and Disability Adjusted Life Year (DALY) estimations. This study identified the professional inactivity caused by the disease as the major loss factor in comparison to the cost of health care and losses due to infected pigs. These findings should allow a simpler estimation of the global disease burden based on information on salary levels and human cysticercosis prevalence in endemic areas of the world. In addition, the number of DALYs lost was higher than estimates already available for some other neglected tropical diseases in sub-Saharan Africa.
doi:10.1371/journal.pntd.0000406
PMCID: PMC2656639  PMID: 19333365
5.  Measuring the Population Burden of Injuries—Implications for Global and National Estimates: A Multi-centre Prospective UK Longitudinal Study 
PLoS Medicine  2011;8(12):e1001140.
Ronan Lyons and colleagues compared the population burden of injuries using different approaches from the UK Burden of Injury and Global Burden of Disease studies and find that the absolute UK burden of injury is higher than previously estimated.
Background
Current methods of measuring the population burden of injuries rely on many assumptions and limited data available to the global burden of diseases (GBD) studies. The aim of this study was to compare the population burden of injuries using different approaches from the UK Burden of Injury (UKBOI) and GBD studies.
Methods and Findings
The UKBOI was a prospective cohort of 1,517 injured individuals that collected patient-reported outcomes. Extrapolated outcome data were combined with multiple sources of morbidity and mortality data to derive population metrics of the burden of injury in the UK. Participants were injured patients recruited from hospitals in four UK cities and towns: Swansea, Nottingham, Bristol, and Guildford, between September 2005 and April 2007. Patient-reported changes in quality of life using the EQ-5D at baseline, 1, 4, and 12 months after injury provided disability weights used to calculate the years lived with disability (YLDs) component of disability adjusted life years (DALYs). DALYs were calculated for the UK and extrapolated to global estimates using both UKBOI and GBD disability weights. Estimated numbers (and rates per 100,000) for UK population extrapolations were 750,999 (1,240) for hospital admissions, 7,982,947 (13,339) for emergency department (ED) attendances, and 22,185 (36.8) for injury-related deaths in 2005. Nonadmitted ED-treated injuries accounted for 67% of YLDs. Estimates for UK DALYs amounted to 1,771,486 (82% due to YLDs), compared with 669,822 (52% due to YLDs) using the GBD approach. Extrapolating patient-derived disability weights to GBD estimates would increase injury-related DALYs 2.6-fold.
Conclusions
The use of disability weights derived from patient experiences combined with additional morbidity data on ED-treated patients and inpatients suggests that the absolute burden of injury is higher than previously estimated. These findings have substantial implications for improving measurement of the national and global burden of injury.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Injuries—resulting from traffic collisions, drowning, poisoning, falls or burns, and violence from assault, self-inflicted violence, or acts of war—kill more than 5 million people worldwide every year and cause harm to millions more. Injuries account for at least 9% of global mortality and are a threat to health in every country of the world. Furthermore, for every death-related injury, dozens of injured people are admitted to hospitals, hundreds visit emergency rooms, and thousands go to see their doctors by appointment. A large proportion of people surviving their injuries will be left with temporary or permanent disabilities.
The Global Burden of Diseases, Injuries and Risk Factors (GBD) Studies are instrumental in quantifying the burden of injuries placed on society and are essential for the public health response, priority setting, and policy development. Central to the GBD methodology is the concept of Disability Adjusted Life years (DALYs), and a combination of premature mortality, referred to as years of life lost and years lived with disability. However, rather than evidence and measurements, the GBD Study used panel studies and expert opinion to estimate weights and durations of disability. Therefore, although the GBD has been a major development, it may have underestimated the population burden.
Why Was This Study Done?
Accurate measurement of the burden of injuries is essential to ensure adequate policy responses to prevention and treatment. In this study, the researchers aimed to overcome the limitations of previous studies and for the first time, measured the population burden of injuries in the UK using a combination of disability and morbidity metrics, including years of life lost, and years lived with disabilities.
What Did the Researchers Do and Find?
The researchers recruited patients aged over 5 years with a wide range of injuries (including fractures and dislocations, lacerations, bruises and abrasions, sprains, burns and scalds, and head, eye, thorax, and abdominal injuries) from hospitals in four English cities—Swansea, Nottingham, Bristol, and Guildford—between September 2005 and April 2007. The researchers collected data on injury-related mortality, hospital admissions, and attendances to emergency rooms. They also invited patients (or their proxy, if participants were young children) to complete a self-administered questionnaire at recruitment and at 1, 4, and 12 months postinjury to allow data collection on injury characteristics, use of health and social services, time off work, and recovery from injury, in addition to sociodemographic and economic and occupational characteristics. The researchers also used standardized tools to measure health-related quality of life and work problems. Then, the researchers used these patient-reported changes to calculate DALYs for the UK and then extrapolated these results to calculate global estimates.
In the four study sites, a total of 1,517 injured people (median age of 37.4 years and 53.9% male) participated in the study. The researchers found that the vast majority of injuries were unintentional and that the home was the most frequent location of injury. Using the data and information collected from the questionnaires, the researchers extrapolated their results and found that in 2005, there were an estimated 750,999 injury-related hospital admissions, 7,982,947 emergency room attendances, and 22,185 injury-related deaths, translating to a rate per 100,000 of 1,240, 13,339, and 36.8, respectively. The researchers estimated UK DALYs related to injury to be 1,771,486 compared with 669,822 using the GBD approach. Furthermore, the researchers found that extrapolating patient-derived disability weights to GBD estimates would increase injury-related DALYs 2.6-fold.
What Do These Findings Mean?
The findings of this study suggest that, when using data and information derived from patient experiences, combined with additional morbidity data on patients treated in emergency rooms and those, admitted to hospital, the absolute burden of injury is higher than previously estimated. While this study was carried out in the UK the principal findings are relevant to other countries. However, measurement of the population burden of injuries requires access to high quality data, which may be difficult in less affluent countries, and these data rely on access to health facilities, which is often restricted in resource-limited settings. Despite these concerns, these findings have substantial implications for improving measurements of the national and global burden of injury.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001140.
The World Health Organization website provides detailed information about injuries and also details the work of the Global Burden of Disease Study
The Global Burden of Injury's website is a portal to websites run by groups conducting ongoing research into the measurement of global injury metrics
doi:10.1371/journal.pmed.1001140
PMCID: PMC3232198  PMID: 22162954
6.  Estimating the Global Clinical Burden of Plasmodium falciparum Malaria in 2007 
PLoS Medicine  2010;7(6):e1000290.
Simon Hay and colleagues derive contemporary estimates of the global clinical burden of Plasmodium falciparum malaria (the deadliest form of malaria) using cartography-based techniques.
Background
The epidemiology of malaria makes surveillance-based methods of estimating its disease burden problematic. Cartographic approaches have provided alternative malaria burden estimates, but there remains widespread misunderstanding about their derivation and fidelity. The aims of this study are to present a new cartographic technique and its application for deriving global clinical burden estimates of Plasmodium falciparum malaria for 2007, and to compare these estimates and their likely precision with those derived under existing surveillance-based approaches.
Methods and Findings
In seven of the 87 countries endemic for P. falciparum malaria, the health reporting infrastructure was deemed sufficiently rigorous for case reports to be used verbatim. In the remaining countries, the mapped extent of unstable and stable P. falciparum malaria transmission was first determined. Estimates of the plausible incidence range of clinical cases were then calculated within the spatial limits of unstable transmission. A modelled relationship between clinical incidence and prevalence was used, together with new maps of P. falciparum malaria endemicity, to estimate incidence in areas of stable transmission, and geostatistical joint simulation was used to quantify uncertainty in these estimates at national, regional, and global scales.
Combining these estimates for all areas of transmission risk resulted in 451 million (95% credible interval 349–552 million) clinical cases of P. falciparum malaria in 2007. Almost all of this burden of morbidity occurred in areas of stable transmission. More than half of all estimated P. falciparum clinical cases and associated uncertainty occurred in India, Nigeria, the Democratic Republic of the Congo (DRC), and Myanmar (Burma), where 1.405 billion people are at risk.
Recent surveillance-based methods of burden estimation were then reviewed and discrepancies in national estimates explored. When these cartographically derived national estimates were ranked according to their relative uncertainty and replaced by surveillance-based estimates in the least certain half, 98% of the global clinical burden continued to be estimated by cartographic techniques.
Conclusions and Significance
Cartographic approaches to burden estimation provide a globally consistent measure of malaria morbidity of known fidelity, and they represent the only plausible method in those malaria-endemic countries with nonfunctional national surveillance. Unacceptable uncertainty in the clinical burden of malaria in only four countries confounds our ability to evaluate needs and monitor progress toward international targets for malaria control at the global scale. National prevalence surveys in each nation would reduce this uncertainty profoundly. Opportunities for further reducing uncertainty in clinical burden estimates by hybridizing alternative burden estimation procedures are also evaluated.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Malaria is a major global public-health problem. Nearly half the world's population is at risk of malaria, and Plasmodium falciparum malaria—the deadliest form of the disease—causes about one million deaths each year. Malaria is a parasitic disease that is transmitted to people through the bite of an infected mosquito. These insects inject a parasitic form known as sporozoites into people, where they replicate briefly inside liver cells. The liver cells then release merozoites (another parasitic form), which invade red blood cells. Here, the merozoites replicate rapidly before bursting out and infecting more red blood cells. This increase in the parasitic burden causes malaria's characteristic symptoms—debilitating and recurring fevers and chills. Infected red blood cells also release gametocytes, which infect mosquitoes when they take a blood meal. In the mosquito, the gametocytes multiply and develop into sporozoites, thus completing the parasite's life cycle. Malaria can be prevented by controlling the mosquitoes that spread the parasite and by avoiding mosquito bites. Effective treatment with antimalarial drugs also helps to reduce malaria transmission.
Why Was This Study Done?
In 1998, the World Health Organization (WHO) and several other international agencies launched Roll Back Malaria, a global partnership that aims to provide a coordinated, global approach to fighting malaria. For this or any other malaria control initiative to be effective, however, an accurate picture of the global clinical burden of malaria (how many people become ill because of malaria and where they live) is needed so that resources can be concentrated where they will have the most impact. Estimates of the global burden of many infectious diseases are obtained using data collected by national surveillance systems. Unfortunately, this approach does not work very well for malaria because in places where malaria is endemic (always present), diagnosis is often inaccurate and national reporting is incomplete. In this study, therefore, the researchers use an alternative, “cartographic” method for estimating the global clinical burden of P. falciparum malaria.
What Did the Researchers Do and Find?
The researchers identified seven P. falciparum malaria-endemic countries that had sufficiently reliable health information systems to determine the national clinical malaria burden in 2007 directly. They divided the other 80 malaria endemic countries into countries with a low risk of transmission (unstable transmission) and countries with a moderate or high risk of transmission (stable transmission). In countries with unstable transmission, the researchers assumed a uniform annual clinical incidence rate of 0.1 cases per 1,000 people and multiplied this by population sizes to get disease burden estimates. In countries with stable transmission, they used a modeled relationship between clinical incidence (number of new cases in a population per year) and prevalence (the proportion of a population infected with malaria parasites) and a global malaria endemicity map (a map that indicates the risk of malaria infection in different countries) to estimate malaria incidences. Finally, they used a technique called “joint simulation” to quantify the uncertainty in these estimates. Together, these disease burden estimates gave an estimated global burden of 451 million clinical cases of P. falciparum in 2007. Most of these cases occurred in areas of stable transmission and more than half occurred in India, Nigeria, the Democratic Republic of the Congo, and Myanmar. Importantly, these four nations alone contributed nearly half of the uncertainty in the global incidence estimates.
What Do These Findings Mean?
These findings are extremely valuable because they provide a global map of malaria cases that should facilitate the implementation and evaluation of malaria control programs. However, the estimate of the global clinical burden of P. falciparum malaria reported here is higher than the WHO estimate of 247 million cases each year that was obtained using surveillance-based methods. The discrepancy between the estimates obtained using the cartographic and the surveillance-based approach is particularly marked for India. The researchers discuss possible reasons for these discrepancies and suggest improvements that could be made to both methods to increase the validity and precision of estimates. Finally, they note that improvements in the national prevalence surveys in India, Nigeria, the Democratic Republic of the Congo, and Myanmar would greatly reduce the uncertainty associated with their estimate of the global clinical burden of malaria, an observation that should encourage efforts to improve malaria surveillance in these countries.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000261.
A PLoS Medicine Health in Action article by Hay and colleagues, a Research Article by Guerra and colleagues, and a Research Article by Hay and colleagues provide further details about the global mapping of malaria risk
Additional national and regional level maps and more information on the global mapping of malaria are available at the Malaria Atlas Project
Information is available from the World Health Organization on malaria (in several languages)
The US Centers for Disease Control and Prevention provide information on malaria (in English and Spanish)
Information is available from the Roll Back Malaria Partnership on its approach to the global control of malaria (in English and French)
MedlinePlus provides links to additional information on malaria (in English and Spanish)
doi:10.1371/journal.pmed.1000290
PMCID: PMC2885984  PMID: 20563310
7.  Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study 2010 
Lancet  2014;383(9913):245-254.
Summary
Background
Although stroke is the second leading cause of death worldwide, no comprehensive and comparable assessment of incidence, prevalence, mortality, disability, and epidemiological trends has been estimated for most regions. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the global and regional burden of stroke during 1990–2010.
Methods
We searched Medline, Embase, LILACS, Scopus, PubMed, Science Direct, Global Health Database, the WHO library, and WHO regional databases from 1990 to 2012 to identify relevant studies published between 1990 and 2010. We applied the GBD 2010 analytical technique (DisMod-MR), based on disease-specific, pre-specified associations between incidence, prevalence, and mortality, to calculate regional and country-specific estimates of stroke incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) lost by age group (<75 years, ≥75 years, and in total) and country income level (high-income, and low-income and middle-income) for 1990, 2005, and 2010.
Findings
We included 119 studies (58 from high-income countries and 61 from low-income and middle-income countries). From 1990 to 2010, the age-standardised incidence of stroke significantly decreased by 12% (95% CI 6–17) in high-income countries, and increased by 12% (–3 to 22) in low-income and middle-income countries, albeit non-significantly. Mortality rates decreased significantly in both high income (37%, 31–41) and low-income and middle-income countries (20%, 15–30). In 2010, the absolute numbers of people with first stroke (16·9 million), stroke survivors (33 million), stroke-related deaths (5·9 million), and DALYs lost (102 million) were high and had significantly increased since 1990 (68%, 84%, 26%, and 12% increase, respectively), with most of the burden (68·6% incident strokes, 52·2% prevalent strokes, 70·9% stroke deaths, and 77·7% DALYs lost) in low-income and middle-income countries. In 2010, 5·2 million (31%) strokes were in children (aged <20 years old) and young and middle-aged adults (20–64 years), to which children and young and middle-aged adults from low-income and middle-income countries contributed almost 74 000 (89%) and 4·0 million (78%), respectively, of the burden. Additionally, we noted significant geographical differences of between three and ten times in stroke burden between GBD regions and countries. More than 62% of new strokes, 69·8% of prevalent strokes, 45·5% of deaths from stroke, and 71·7% of DALYs lost because of stroke were in people younger than 75 years.
Interpretation
Although age-standardised rates of stroke mortality have decreased worldwide in the past two decades, the absolute number of people who have a stroke every year, stroke survivors, related deaths, and the overall global burden of stroke (DALYs lost) are great and increasing. Further study is needed to improve understanding of stroke determinants and burden worldwide, and to establish causes of disparities and changes in trends in stroke burden between countries of different income levels.
Funding
Bill & Melinda Gates Foundation.
PMCID: PMC4181600  PMID: 24449944
8.  Characterizing the Epidemiological Transition in Mexico: National and Subnational Burden of Diseases, Injuries, and Risk Factors 
PLoS Medicine  2008;5(6):e125.
Background
Rates of diseases and injuries and the effects of their risk factors can have substantial subnational heterogeneity, especially in middle-income countries like Mexico. Subnational analysis of the burden of diseases, injuries, and risk factors can improve characterization of the epidemiological transition and identify policy priorities.
Methods and Findings
We estimated deaths and loss of healthy life years (measured in disability-adjusted life years [DALYs]) in 2004 from a comprehensive list of diseases and injuries, and 16 major risk factors, by sex and age for Mexico and its states. Data sources included the vital statistics, national censuses, health examination surveys, and published epidemiological studies. Mortality statistics were adjusted for underreporting, misreporting of age at death, and for misclassification and incomparability of cause-of-death assignment. Nationally, noncommunicable diseases caused 75% of total deaths and 68% of total DALYs, with another 14% of deaths and 18% of DALYs caused by undernutrition and communicable, maternal, and perinatal diseases. The leading causes of death were ischemic heart disease, diabetes mellitus, cerebrovascular disease, liver cirrhosis, and road traffic injuries. High body mass index, high blood glucose, and alcohol use were the leading risk factors for disease burden, causing 5.1%, 5.0%, and 7.3% of total burden of disease, respectively. Mexico City had the lowest mortality rates (4.2 per 1,000) and the Southern region the highest (5.0 per 1,000); under-five mortality in the Southern region was nearly twice that of Mexico City. In the Southern region undernutrition and communicable, maternal, and perinatal diseases caused 23% of DALYs; in Chiapas, they caused 29% of DALYs. At the same time, the absolute rates of noncommunicable disease and injury burdens were highest in the Southern region (105 DALYs per 1,000 population versus 97 nationally for noncommunicable diseases; 22 versus 19 for injuries).
Conclusions
Mexico is at an advanced stage in the epidemiologic transition, with the majority of the disease and injury burden from noncommunicable diseases. A unique characteristic of the epidemiological transition in Mexico is that overweight and obesity, high blood glucose, and alcohol use are responsible for larger burden of disease than other noncommunicable disease risks such as tobacco smoking. The Southern region is least advanced in the epidemiological transition and suffers from the largest burden of ill health in all disease and injury groups.
Gretchen Stevens and colleagues estimate deaths and loss of healthy life years (measured in disability-adjusted life years, DALYs) for Mexico as a whole and its 32 states.
Editors' Summary
Background.
The impact that a particular disease has upon a population is known as the “burden of disease.” This burden is estimated by considering how many deaths the disease causes and how much it disables those still living. The relative contributions of different diseases and injuries to the loss of healthy life from death and disability vary greatly among countries. Broadly speaking, in low-income countries (such as many African countries), infectious diseases and undernutrition are the major causes of ill health and death whereas in high-income countries (for example, the United States), noncommunicable diseases such as heart disease, diabetes, and stroke are more important. As poor countries become richer, they experience a change in the pattern of disease away from infectious diseases and malnutrition and toward noncommunicable diseases. Health experts call this change the “epidemiological transition” (epidemiology is the study of the distribution and causes of diseases in populations). Governments need to know as much as possible about which diseases have the greatest burden—and about where the country is in the epidemiological transition—to help them implement effective health policies. For example, there is no point in setting up treatment centers for a specific infectious disease in a country where the disease no longer occurs. Equally importantly, governments need to know which lifestyle choices and other genetic and environmental factors affect the chances of people in their country developing specific diseases so that they can provide relevant educational and intervention programs.
Why Was This Study Done?
Most analyses of the burden of disease have been done at the national and global scale. However, in middle-income countries, different regions of the country may be at different stages of the epidemiological transition and may, therefore, have very different patterns of disease. In this study, the researchers investigate whether this is the case for Mexico, a middle-income country that has developed rapidly over the past few decades. Mexico recently reformed its health system to improve access to health care for the poor and underserved. Under this new system, individual states play an important role in allocating health-care resources (as they do in many other countries) so it is very important to know how the burden of disease varies in different states of the country.
What Did the Researchers Do and Find?
The researchers estimated deaths and loss of healthy life years caused by various diseases and injuries for Mexico and its states using data from death registers, censuses, health examination surveys, and epidemiological studies. Loss of healthy life years was measured using a metric called “disability-adjusted life years” (DALYs)—one DALY is equivalent to the loss of one year of healthy life because of premature death or disability. They also identified the major risk factors for these diseases and injuries across the country. Nationally, noncommunicable diseases (particularly heart disease, diabetes, stroke, and liver cirrhosis) caused 75% of deaths and 68% of DALYs. Undernutrition, infectious diseases, and problems occurring in mothers and infants around the time of birth (maternal and perinatal diseases) caused 14% of deaths and 18% of DALYs. The leading risk factors for disease in Mexico were being overweight, having high blood glucose, and alcohol use. When the researchers studied different regions of the country, they found that Mexico City had the lowest death rate whereas the relatively undeveloped Southern region of Mexico had the highest, particularly among young children. In Chiapas, the most southerly state of Mexico, undernutrition and infectious, maternal, and perinatal diseases caused nearly a third of DALYs. In addition to the highest infectious disease burden, the Southern region also had the highest noncommunicable disease and injury burden per head of population.
What Do These Findings Mean?
These findings indicate that Mexico as a nation is at an advanced stage of the epidemiological transition. In other words, because of the improvement in its economic status, the burden of disease caused by infectious diseases and undernutrition has decreased, and noncommunicable diseases now cause the largest share of the total burden of disease. However, the study also shows that the poorest regions of the country, which have the highest overall burden of disease, are lagging behind the richer regions in terms of their position in the epidemiological transition. Thus different health priorities need to be set in different regions of Mexico (and in other middle-income countries where the burden of disease is also likely to vary with region). Finally, the information provided by this study about the forces driving the epidemiological transition in Mexico, such as the importance of obesity and alcohol use, should help public-health officials decide how to improve the overall health of the Mexican population.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050125.
A related PLoS Medicine Perspective by Martin Tobias further discusses this research
The World Health Organization provides information on the Global Burden of Disease Project including links to other burden of disease resources. It also provides detailed information on various aspects of health in Mexico (in several languages), and an explanation of DALYs
Read a detailed article on the “epidemiological transition” by Abdel Omran, who proposed this idea in 1971
A large amount of Mexican data is available online for Spanish speakers. Complete raw mortality statistics can be found on the Mexican Ministry of Health's Web site http://sinais.salud.gob.mx/sinais.php. Also online is the complete report of the ENSANUT survey (Encuesta Nacional de Salud y Nutrición 2006) http://www.insp.mx/ensanut/, which was one of the major data sources used to determine risk factor exposure
doi:10.1371/journal.pmed.0050125
PMCID: PMC2429945  PMID: 18563960
9.  Burden of Disease from Toxic Waste Sites in India, Indonesia, and the Philippines in 2010 
Environmental Health Perspectives  2013;121(7):791-796.
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.
doi:10.1289/ehp.1206127
PMCID: PMC3702002  PMID: 23649493
Asia; burden of disease; chemical exposure; disability-adjusted life year; toxic waste sites
10.  Estimating and validating disability-adjusted life years at the global level: a methodological framework for cancer 
Background
Disability-adjusted life years (DALYs) link data on disease occurrence to health outcomes, and they are a useful aid in establishing country-specific agendas regarding cancer control. The variables required to compute DALYs are however multiple and not readily available in many countries. We propose a methodology that derives global DALYs and validate variables and DALYs based on data from various cancer registries.
Methods
We estimated DALYs for four countries (Norway, Bulgaria, India and Uganda) within each category of the human development index (HDI). The following sources (indicators) were used: Globocan2008 (incidence and mortality), various cancer registries (proportion cured, proportion treated and duration of disease), treatment guidelines (duration of treatment), specific burden of disease studies (sequelae and disability weights), alongside expert opinion. We obtained country-specific population estimates and identified resource levels using the HDI, DALYs are computed as the sum of years of life lost and years lived with disabilities.
Results
Using mortality:incidence ratios to estimate country-specific survival, and by applying the human development index we derived country-specific estimates of the proportion cured and the proportion treated. The fit between the estimates and observed data from the cancer registries was relatively good. The final DALY estimates were similar to those computed using observed values in Norway, and in WHO’s earlier global burden of disease study. Marked cross-country differences in the patterns of DALYs by cancer sites were observed. In Norway and Bulgaria, breast, colorectal, prostate and lung cancer were the main contributors to DALYs, representing 54% and 45%, respectively, of the totals. These cancers contributed only 27% and 18%, respectively, of total DALYs in India and Uganda.
Conclusions
Our approach resulted in a series of variables that can be used to estimate country-specific DALYs, enabling global estimates of DALYs and international comparisons that support priorities in cancer control.
doi:10.1186/1471-2288-12-125
PMCID: PMC3490831  PMID: 22901001
Years of life live with disability; Years of life lost; Disability-adjusted life years; Cancer; Global estimates
11.  Global Socioeconomic Impact of Cystic Echinococcosis 
Emerging Infectious Diseases  2006;12(2):296-303.
Because the human and economic losses of cystic echinococcosis are substantial, global prevention and control measures should be increased.
Cystic echinococcosis (CE) is an emerging zoonotic parasitic disease throughout the world. Human incidence and livestock prevalence data of CE were gathered from published literature and the Office International des Epizooties databases. Disability-adjusted life years (DALYs) and monetary losses, resulting from human and livestock CE, were calculated from recorded human and livestock cases. Alternative values, assuming substantial underreporting, are also reported. When no underreporting is assumed, the estimated human burden of disease is 285,407 (95% confidence interval [CI], 218,515–366,133) DALYs or an annual loss of US $193,529,740 (95% CI, $171,567,331–$217,773,513). When underreporting is accounted for, this amount rises to 1,009,662 (95% CI, 862,119–1,175,654) DALYs or US $763,980,979 (95% CI, $676,048,731–$857,982,275). An annual livestock production loss of at least US $141,605,195 (95% CI, $101,011,553–$183,422,465) and possibly up to US $2,190,132,464 (95% CI, $1,572,373,055–$2,951,409,989) is also estimated. This initial valuation demonstrates the necessity for increased monitoring and global control of CE.
doi:10.3201/eid1202.050499
PMCID: PMC3373106  PMID: 16494758
echinococcosis; cestodes; cost of illness; burden of illness; economics; zoonoses
12.  Incorporating Scale Dependence in Disease Burden Estimates: The Case of Human African Trypanosomiasis in Uganda 
Background
The WHO has established the disability-adjusted life year (DALY) as a metric for measuring the burden of human disease and injury globally. However, most DALY estimates have been calculated as national totals. We mapped spatial variation in the burden of human African trypanosomiasis (HAT) in Uganda for the years 2000–2009. This represents the first geographically delimited estimation of HAT disease burden at the sub-country scale.
Methodology/Principal Findings
Disability-adjusted life-year (DALY) totals for HAT were estimated based on modelled age and mortality distributions, mapped using Geographic Information Systems (GIS) software, and summarised by parish and district. While the national total burden of HAT is low relative to other conditions, high-impact districts in Uganda had DALY rates comparable to the national burden rates for major infectious diseases. The calculated average national DALY rate for 2000–2009 was 486.3 DALYs/100 000 persons/year, whereas three districts afflicted by rhodesiense HAT in southeastern Uganda had burden rates above 5000 DALYs/100 000 persons/year, comparable to national GBD 2004 average burden rates for malaria and HIV/AIDS.
Conclusions/Significance
These results provide updated and improved estimates of HAT burden across Uganda, taking into account sensitivity to under-reporting. Our results highlight the critical importance of spatial scale in disease burden analyses. National aggregations of disease burden have resulted in an implied bias against highly focal diseases for which geographically targeted interventions may be feasible and cost-effective. This has significant implications for the use of DALY estimates to prioritize disease interventions and inform cost-benefit analyses.
Author Summary
Since the 1990s the World Health Organisation has established the disability-adjusted life year (DALY) as a metric for the burden of human disease and injury. However, disease burden has primarily been estimated at the national scale, which does not account for sub-country variations in burden levels. We used the case of human African trypanosomiasis (HAT), a highly focal NTD, in Uganda to calculate and map burden in DALYs. Our results show that HAT burden is highly sensitive to under-reporting estimates, and is particularly high in heavily affected parishes and districts of Uganda. Some districts in southeastern Uganda had HAT burden rates comparable to the national burden rates of major infectious diseases such as malaria and HIV/AIDS. Thus, the spatial scale of burden estimation is crucial, especially for focal diseases such as HAT, and national-level estimates may not reflect the level of impact in afflicted communities. We recommend sub-country burden estimation to identify key areas for prioritization of disease surveillance and targeted interventions.
doi:10.1371/journal.pntd.0002704
PMCID: PMC3923749  PMID: 24551264
13.  Quantifying the Burden of Rhodesiense Sleeping Sickness in Urambo District, Tanzania 
Background
Human African trypanosomiasis is a severely neglected vector-borne disease that is always fatal if untreated. In Tanzania it is highly focalised and of major socio-economic and public health importance in affected communities.
Objectives
This study aimed to estimate the public health burden of rhodesiense HAT in terms of DALYs and financial costs in a highly disease endemic area of Tanzania using hospital records.
Materials and Methods
Data was obtained from 143 patients admitted in 2004 for treatment for HAT at Kaliua Health Centre, Urambo District. The direct medical and other indirect costs incurred by individual patients and by the health services were calculated. DALYs were estimated using methods recommended by the Global Burden of Disease Project as well as those used in previous rhodesiense HAT estimates assuming HAT under reporting of 45%, a figure specific for Tanzania.
Results
The DALY estimate for HAT in Urambo District with and without age-weighting were 215.7 (95% CI: 155.3–287.5) and 281.6 (95% CI: 209.1–362.6) respectively. When 45% under-reporting was included, the results were 622.5 (95% CI: 155.3–1098.9) and 978.9 (95% CI: 201.1–1870.8) respectively. The costs of treating 143 patients in terms of admission costs, diagnosis, hospitalization and sleeping sickness drugs were estimated at US$ 15,514, of which patients themselves paid US$ 3,673 and the health services US$ 11,841. The burden in terms of indirect non-medical costs for the 143 patients was estimated at US$ 9,781.
Conclusions
This study shows that HAT imposes a considerable burden on affected rural communities in Tanzania and stresses the urgent need for location- and disease-specific burden estimates tailored to particular rural settings in countries like Tanzania where a considerable number of infectious diseases are prevalent and, due to their focal nature, are often concentrated in certain locations where they impose an especially high burden.
Author Summary
Sleeping sickness (human African trypanosomiasis - HAT) is a disease transmitted by tsetse flies and is always fatal if left untreated. The disease occurs in foci affecting poor communities with limited access to health service provision and as such the disease is often left undiagnosed, mistaken for more common afflictions. Even if diagnosed, sleeping sickness is costly to treat, both for health services and patients and their families in terms of costs of diagnosis, transport, hospital care, and the prolonged period of convalescence. Here we estimate the health burden of the “acute form” T. b. rhodesiense sleeping sickness in Urambo District, Tanzania in terms of Disability Adjusted Life Years (DALYs), the yardstick commonly used by policy makers to prioritize disease management practices, representing a year of healthy life lost to disease. In this single district, the burden of the disease over one year was estimated at 979 DALYs and the estimated monetary costs to health services for the 143 treated patients at US$ 11,841 and to the patients themselves at US$ 3,673 for direct medical costs and US$ 9,781 for indirect non-medical costs. Sleeping sickness thus places a considerable burden on the affected rural communities and health services.
doi:10.1371/journal.pntd.0000868
PMCID: PMC2970539  PMID: 21072230
14.  The Pathogen- and Incidence-Based DALY Approach: An Appropriated Methodology for Estimating the Burden of Infectious Diseases 
PLoS ONE  2013;8(11):e79740.
In 2009, the European Centre for Disease Prevention and Control initiated the ‘Burden of Communicable Diseases in Europe (BCoDE)’ project to generate evidence-based and comparable burden-of-disease estimates of infectious diseases in Europe. The burden-of-disease metric used was the Disability-Adjusted Life Year (DALY), composed of years of life lost due to premature death (YLL) and due to disability (YLD). To better represent infectious diseases, a pathogen-based approach was used linking incident cases to sequelae through outcome trees. Health outcomes were included if an evidence-based causal relationship between infection and outcome was established. Life expectancy and disability weights were taken from the Global Burden of Disease Study and alternative studies. Disease progression parameters were based on literature. Country-specific incidence was based on surveillance data corrected for underestimation. Non-typhoidal Salmonella spp. and Campylobacter spp. were used for illustration. Using the incidence- and pathogen-based DALY approach the total burden for Salmonella spp. and Campylobacter spp. was estimated at 730 DALYs and at 1,780 DALYs per year in the Netherlands (average of 2005–2007). Sequelae accounted for 56% and 82% of the total burden of Salmonella spp. and Campylobacter spp., respectively. The incidence- and pathogen-based DALY methodology allows in the case of infectious diseases a more comprehensive calculation of the disease burden as subsequent sequelae are fully taken into account. Not considering subsequent sequelae would strongly underestimate the burden of infectious diseases. Estimates can be used to support prioritisation and comparison of infectious diseases and other health conditions, both within a country and between countries.
doi:10.1371/journal.pone.0079740
PMCID: PMC3835936  PMID: 24278167
15.  The Global Burden of Snakebite: A Literature Analysis and Modelling Based on Regional Estimates of Envenoming and Deaths 
PLoS Medicine  2008;5(11):e218.
Background
Envenoming resulting from snakebites is an important public health problem in many tropical and subtropical countries. Few attempts have been made to quantify the burden, and recent estimates all suffer from the lack of an objective and reproducible methodology. In an attempt to provide an accurate, up-to-date estimate of the scale of the global problem, we developed a new method to estimate the disease burden due to snakebites.
Methods and Findings
The global estimates were based on regional estimates that were, in turn, derived from data available for countries within a defined region. Three main strategies were used to obtain primary data: electronic searching for publications on snakebite, extraction of relevant country-specific mortality data from databases maintained by United Nations organizations, and identification of grey literature by discussion with key informants. Countries were grouped into 21 distinct geographic regions that are as epidemiologically homogenous as possible, in line with the Global Burden of Disease 2005 study (Global Burden Project of the World Bank). Incidence rates for envenoming were extracted from publications and used to estimate the number of envenomings for individual countries; if no data were available for a particular country, the lowest incidence rate within a neighbouring country was used. Where death registration data were reliable, reported deaths from snakebite were used; in other countries, deaths were estimated on the basis of observed mortality rates and the at-risk population. We estimate that, globally, at least 421,000 envenomings and 20,000 deaths occur each year due to snakebite. These figures may be as high as 1,841,000 envenomings and 94,000 deaths. Based on the fact that envenoming occurs in about one in every four snakebites, between 1.2 million and 5.5 million snakebites could occur annually.
Conclusions
Snakebites cause considerable morbidity and mortality worldwide. The highest burden exists in South Asia, Southeast Asia, and sub-Saharan Africa.
Janaka de Silva and colleagues estimate that globally at least 421,000 envenomings and 20,000 deaths occur each year due to snakebite.
Editors' Summary
Background.
Of the 3,000 or so snake species that exist in the world, about 600 are venomous. Venomous snakes—which exist on every continent except Antarctica—immobilize their prey by injecting modified saliva (venom) that contains toxins into their prey's tissues through their fangs—specialized, hollow teeth. Snakes also use their venoms for self defense and will bite people who threaten, startle or provoke them. Snakebites caused by the families Viperidae (for example, pit vipers) and Elapidae (for example, kraits and cobras) are particularly dangerous to people. The potentially fatal effects of being “envenomed” (having venom injected) by these snakes include widespread bleeding, muscle paralysis, and tissue destruction (necrosis) around the bite site. Bites from these snakes can also cause permanent disability. For example, snakebite victims, who tend to be young and male, may have to have a limb amputated because of necrosis. The best treatment for any snakebite is to get the victim to a hospital as soon as possible where antivenoms (mixtures of antibodies that neutralize venoms) can be given.
Why Was This Study Done?
Although snakebites occur throughout the world, envenoming snakebites are thought to pose a particularly important yet largely neglected threat to public health. This is especially true in rural areas of tropical and subtropical countries where snakebites are common but where there is limited access to health care and to antivenoms. The true magnitude of the public-health threat posed by snakebites in these countries (and elsewhere in the world) is unknown, which makes it hard for public-health officials to optimize the prevention and treatment of snakebites in their respective countries. In this study, therefore, the researchers develop and apply a new method to estimate the global burden of snakebite.
What Did the Researchers Do and Find?
The researchers systematically searched the scientific literature for publications on snakebites and deaths from snakebites and extracted data on snakebite deaths in individual countries from the World Health Organization (WHO) mortality database. They also contacted Ministries of Health, National Poison Centers, and snakebite experts for unpublished information (“grey” literature) on snakebites. Together, these three approaches provided data on the number of snakebite envenomings and deaths for 135 and 162 countries, respectively. The researchers then grouped the 227 countries of the world into 21 geographical regions, each of which contained countries with similar population characteristics, and used the results of studies done in individual countries within each region to estimate the numbers of snakebite envenomings and deaths for each region. Finally, they added up these estimates to obtain an estimate of the global burden of snakebite. Using this method, the researchers estimate that, worldwide, at least 421,000 envenomings and 20,000 deaths from snakebite occur every year; the actual numbers, they suggest, could be as high as 1.8 million envenomings and 94,000 deaths. Their estimates also indicate that the highest burden of snakebite envenomings and death occurs in South and Southeast Asia and in sub-Saharan Africa, and that India is the country with the highest annual number of envenomings (81,000) and deaths (nearly 11,000).
What Do These Findings Mean?
These findings indicate that snakebites cause considerable illness and death around the world. Because of the careful methods used by the researchers, their global estimates of snakebite envenomings and deaths are probably more accurate than previous estimates. However, because the researchers had to make many assumptions in their calculations and because there are so few reliable data on the numbers of snakebites and deaths from the rural tropics, the true regional and global numbers of these events may differ substantially from the estimates presented here. In particular, the regional estimates for eastern sub-Saharan Africa, a region where snakebites are very common and where antivenoms are particularly hard to obtain, are likely to be inaccurate because they are based on a single study. The researchers, therefore, call for more studies on snakebite envenoming and deaths to be done to provide the information needed to deal effectively with this neglected public-health problem.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050218.
This study is further discussed in a PLoS Medicine Perspective by Chippaux
The MedlinePlus Medical Encyclopedia has a page on snakebites (in English and Spanish)
The UK National Health Service Direct health encyclopedia has detailed information about all aspects of snakebites
Wikipedia has pages on venomous snakes and on snakebites (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The World Health Organization provides information about antivenoms and about efforts to increase access to antivenoms in developing countries (available in several languages)
A previous article in PLoS Medicine also discusses the neglected problem of snakebite envenoming: Gutiérrez JM, Theakston RDG, Warrell DA (2006) Confronting the Neglected Problem of Snake Bite Envenoming: The Need for a Global Partnership. PLoS Med 3(6): e150
doi:10.1371/journal.pmed.0050218
PMCID: PMC2577696  PMID: 18986210
16.  Burden of epilepsy in rural Kenya measured in disability-adjusted life years 
Epilepsia  2014;55(10):1626-1633.
Objectives
The burden of epilepsy, in terms of both morbidity and mortality, is likely to vary depending on the etiology (primary [genetic/unknown] vs. secondary [structural/metabolic]) and with the use of antiepileptic drugs (AEDs). We estimated the disability-adjusted life years (DALYs) and modeled the remission rates of active convulsive epilepsy (ACE) using epidemiologic data collected over the last decade in rural Kilifi, Kenya.
Methods
We used measures of prevalence, incidence, and mortality to model the remission of epilepsy using disease-modeling software (DisMod II). DALYs were calculated as the sum of Years Lost to Disability (YLD) and Years of Life Lost (YLL) due to premature death using the prevalence approach, with disability weights (DWs) from the 2010 Global Burden of Disease (GBD) study. DALYs were calculated with R statistical software with the associated uncertainty intervals (UIs) computed by bootstrapping.
Results
A total of 1,005 (95% UI 797–1,213) DALYs were lost to ACE, which is 433 (95% UI 393–469) DALYs lost per 100,000 people. Twenty-six percent (113/100,000/year, 95% UI 106–117) of the DALYs were due to YLD and 74% (320/100,000/year, 95% UI 248–416) to YLL. Primary epilepsy accounted for fewer DALYs than secondary epilepsy (98 vs. 334 DALYs per 100,000 people). Those taking AEDs contributed fewer DALYs than those not taking AEDs (167 vs. 266 DALYs per 100,000 people). The proportion of people with ACE in remission per year was estimated at 11.0% in males and 12.0% in females, with highest rates in the 0–5 year age group.
Significance
The DALYs for ACE are high in rural Kenya, but less than the estimates of 2010 GBD study. Three-fourths of DALYs resulted from secondary epilepsy. Use of AEDs was associated with 40% reduction of DALYs. Improving adherence to AEDs may reduce the burden of epilepsy in this area.
doi:10.1111/epi.12741
PMCID: PMC4238788  PMID: 25131901
Burden; Disability-adjusted life years; Epilepsy; Remission; Treatment gap
17.  Global economic burden of Chagas disease: a computational simulation model 
The Lancet infectious diseases  2013;13(4):342-348.
Summary
Background
As Chagas disease continues to expand beyond tropical and subtropical zones, a growing need exists to better understand its resulting economic burden to help guide stakeholders such as policy makers, funders, and product developers. We developed a Markov simulation model to estimate the global and regional health and economic burden of Chagas disease from the societal perspective.
Methods
Our Markov model structure had a 1 year cycle length and consisted of five states: acute disease, indeterminate disease, cardiomyopathy with or without congestive heart failure, megaviscera, and death. Major model parameter inputs, including the annual probabilities of transitioning from one state to another, and present case estimates for Chagas disease came from various sources, including WHO and other epidemiological and disease-surveillance-based reports. We calculated annual and lifetime health-care costs and disability-adjusted life-years (DALYs) for individuals, countries, and regions. We used a discount rate of 3% to adjust all costs and DALYs to present-day values.
Findings
On average, an infected individual incurs US$474 in health-care costs and 0·51 DALYs annually. Over his or her lifetime, an infected individual accrues an average net present value of $3456 and 3·57 DALYs. Globally, the annual burden is $627·46 million in health-care costs and 806 170 DALYs. The global net present value of currently infected individuals is $24·73 billion in health-care costs and 29 385 250 DALYs. Conversion of this burden into costs results in annual per-person costs of $4660 and lifetime per-person costs of $27 684. Global costs are $7·19 billion per year and $188·80 billion per lifetime. More than 10% of these costs emanate from the USA and Canada, where Chagas disease has not been traditionally endemic. A substantial proportion of the burden emerges from lost productivity from cardiovascular disease-induced early mortality.
Interpretation
The economic burden of Chagas disease is similar to or exceeds those of other prominent diseases globally (eg, rotavirus $2·0 billion, cervical cancer $4·7 billion) even in the USA (Lyme disease $2·5 billion), where Chagas disease has not been traditionally endemic, suggesting an economic argument for more attention and efforts towards control of Chagas disease.
Funding
Bill & Melinda Gates Foundation, the National Institute of General Medical Sciences Models of Infectious Disease Agent Study.
doi:10.1016/S1473-3099(13)70002-1
PMCID: PMC3763184  PMID: 23395248
18.  Serological Testing Versus Other Strategies for Diagnosis of Active Tuberculosis in India: A Cost-Effectiveness Analysis 
PLoS Medicine  2011;8(8):e1001074.
This cost-effectiveness study shows that sputum smear microscopy is the most cost-effective test for active tuberculosis (TB) in India, and liquid culture plus microscopy is more cost-effective for TB diagnosis than serological tests.
Background
Undiagnosed and misdiagnosed tuberculosis (TB) drives the epidemic in India. Serological (antibody detection) TB tests are not recommended by any agency, but widely used in many countries, including the Indian private sector. The cost and impact of using serology compared with other diagnostic techniques is unknown.
Methods and Findings
Taking a patient cohort conservatively equal to the annual number of serological tests done in India (1.5 million adults suspected of having active TB), we used decision analysis to estimate costs and effectiveness of sputum smear microscopy (US$3.62 for two smears), microscopy plus automated liquid culture (mycobacterium growth indicator tube [MGIT], US$20/test), and serological testing (anda-tb ELISA, US$20/test). Data on test accuracy and costs were obtained from published literature. We adopted the perspective of the Indian TB control sector and an analysis frame of 1 year. Our primary outcome was the incremental cost per disability-adjusted life year (DALY) averted. We performed one-way sensitivity analysis on all model parameters, with multiway sensitivity analysis on variables to which the model was most sensitive.
If used instead of sputum microscopy, serology generated an estimated 14,000 more TB diagnoses, but also 121,000 more false-positive diagnoses, 102,000 fewer DALYs averted, and 32,000 more secondary TB cases than microscopy, at approximately four times the incremental cost (US$47.5 million versus US$11.9 million). When added to high-quality sputum smears, MGIT culture was estimated to avert 130,000 incremental DALYs at an incremental cost of US$213 per DALY averted. Serology was dominated by (i.e., more costly and less effective than) MGIT culture and remained less economically favorable than sputum smear or TB culture in one-way and multiway sensitivity analyses.
Conclusions
In India, sputum smear microscopy remains the most cost-effective diagnostic test available for active TB; efforts to increase access to quality-assured microscopy should take priority. In areas where high-quality microscopy exists and resources are sufficient, MGIT culture is more cost-effective than serology as an additional diagnostic test for TB. These data informed a recently published World Health Organization policy statement against serological tests.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, about 2 million people develop tuberculosis in India—a fifth of the global incidence of this highly contagious bacterial infection. Mycobacterium tuberculosis, the bacterium that causes tuberculosis, is spread in airborne droplets when people with the disease cough or sneeze and usually infects the lungs although it can also infect other organs. The characteristic symptoms of tuberculosis are a persistent cough, weight loss, and night sweats. Diagnostic tests for tuberculosis include sputum smear microscopy (microscopic analysis of mucus brought up from the lungs by coughing), culture (growth) of M. tuberculosis from sputum samples in liquid media (using, for example, a commercial product called the mycobacteria growth indicator tube or MGIT), and nucleic acid amplification tests (which detect the bacterium's genome in patient samples) such as the Xpert MTB/RIF system. Tuberculosis can usually be cured by taking several powerful antibiotics daily for at least 6 months.
Why Was This Study Done?
In India, as elsewhere, undiagnosed and misdiagnosed tuberculosis drives the tuberculosis epidemic by increasing the transmission of M. tuberculosis. Unfortunately, sputum smear microscopy, the current mainstay of tuberculosis diagnosis worldwide, detects only half of tuberculosis cases, mycobacterial culture can take weeks to provide a diagnosis, and rapid techniques such as nucleic acid amplification require infrastructure that is often not available in developing countries. Consequently, in India and other developing countries, serological tests are widely used for the diagnosis of tuberculosis. Serological tests detect antibodies against M. tuberculosis in the blood (antibodies are proteins made by the immune system in response to infections). Serological tests are fast and simple to perform, but they are not recommended for clinical use, and the available evidence suggests that they do not diagnose tuberculosis accurately. Even so, and in the absence of information about the cost and impact (cost-effectiveness) of serological testing, about 1.5 million serological tests for tuberculosis are conducted every year in India at a cost of more than US$15 million. Here, the researchers analyze the cost-effectiveness of serological tests compared to other diagnostic tests from the perspective of tuberculosis control in India.
What Did the Researchers Do and Find?
The researchers used “decision analysis” to estimate the cost-effectiveness of sputum smear microscopy, microscopy plus liquid culture using the MGIT system, and serological testing using the widely used anda-tb ELISA commercial test in a hypothetical group of 1.5 million people suspected of having tuberculosis. Decision analysis formally assesses the decision-making process by using models that evaluate outcomes under different scenarios. By feeding data on the costs and accuracy of different diagnostic tests into their decision-analysis model, the researchers estimate that, over a year, serology would generate 14,000 more tuberculosis diagnoses than sputum microscopy. However, it would also generate 121,000 more false-positive diagnoses and 32,000 more tuberculosis transmissions to other people (secondary transmissions), and avert 102,000 fewer disability-adjusted life years (DALYs; a DALY is a year of healthy life lost because of premature death or disability) at four times the incremental cost of sputum microscopy. MGIT culture added to sputum smear microscopy would avert 130,000 DALYs at an incremental cost of US$213 per DALY averted. Finally, sensitivity analyses (reruns of the decision-analysis model using different values for test costs and accuracy) identified no scenario in which serology was either less costly or more effective than sputum smear microscopy alone or in which serology plus sputum microscopy was more cost-effective than MGIT culture plus sputum microscopy.
What Do These Findings Mean?
These findings identify sputum smear microscopy as the most cost-effective existing diagnostic test for tuberculosis in India. Moreover, they suggest that in areas where high-quality microscopy is available, resources are sufficient, and infrastructure to effectively use culture exists, the addition of MGIT culture to sputum smear microscopy would be more cost-effective than the addition of serology. Importantly, these findings suggest that, if used as an initial test for tuberculosis in India, serology would result in more DALYs, more secondary infections, and more false-positive diagnoses than sputum smear microscopy while increasing per-patient costs to the Indian tuberculosis control sector. Given these findings and the results of a recent updated systematic review on the accuracy of serological tests, the World Health Organization's Strategic and Technical Advisory Group for Tuberculosis recently advised against the use of currently available serological tests for the diagnosis of tuberculosis. The WHO negative policy against serological tests must now be implemented in India.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001074.
Details of the recent systematic review of serological tests for tuberculosis diagnosis are available in a PLoS Medicine Research Article by Steingart et al.
The World Health Organization provides information on all aspects of tuberculosis, including tuberculosis diagnostics and the Stop TB Partnership (some information is in several languages); its Strategic and Technical Advisory Group for Tuberculosis recommendations on tuberculosis diagnosis are available
The Evidence-based TB Diagnosis Web site by the Stop TB Partnership's New Diagnostics Working Group provides evidence syntheses on various TB tests, along with guidelines, resources, and training materials
The US Centers for Disease Control and Prevention has information about tuberculosis, including information on the diagnosis of tuberculosis disease
The US National Institute of Allergy and Infectious Diseases also has information on all aspects of tuberculosis
MedlinePlus has links to further information about tuberculosis (in English and Spanish)
doi:10.1371/journal.pmed.1001074
PMCID: PMC3153451  PMID: 21857810
19.  NSFC Health Research Funding and Burden of Disease in China 
PLoS ONE  2014;9(11):e111458.
Background
Allocation of health research funds among diseases has never been evaluated in China. This study aimed to examine the relationship between disease-specific funding levels of National Nature Science Foundation of China (NSFC), the main governmental resource for health research in China, and burden of disease.
Methods
Funding magnitudes for 53 diseases or conditions were obtained from the website of NSFC. Measures of disease burden, mortality, years of life lost (YLLs) and disability-adjusted life years (DALYs), were derived from the Global Burden of Disease Study 2010. The relationship between NSFC funding and disease burden was analyzed with univariate linear regression. For each measure associated with funding, regression-derived estimates were used to calculate the expected funds for each disease. The actual and expected funds were then compared. We also evaluated the impacts of changes of disease burden metrics since 1990, and differences from the world averages on NSFC funding.
Results
NSFC health research funding was associated with disease burden measured in mortality (R = 0.33, P = 0.02), YLLs (R = 0.39, P = 0.004), and DALYs (R = 0.40, P = 0.003). But none of the changes of mortality (R = 0.22, P = 0.12), YLLs (R = −0.04, P = 0.79) and DALYs (R = −0.003, P = 0.98) since 1990 was associated with the funding magnitudes. None of the differences of mortality (R = −0.11, P = 0.45), YLLs (R = −0.11, P = 0.43) and DALYs (R = −0.12, P = 0.38) from that of the concurrent world averages were associated with the funding magnitudes. Measured by DALY, stroke and COPD received the least funding compared to expected; while leukemia and diabetes received the most funding compared to expected.
Conclusion
Although NSFC funding were roughly associated with disease burden as measured in mortality, YLLs and DALYs. Some major diseases such as stroke were underfunded; while others such as leukaemia were overfunded. Change of disease burden during the last 20 years and country-specialized disease burden were not reflected in current allocation of NSFC funds.
doi:10.1371/journal.pone.0111458
PMCID: PMC4219749  PMID: 25369330
20.  Integrated disease prevention campaigns: assessing country opportunity for implementation via an index approach 
BMJ Open  2014;4(3):e004308.
Objectives
To help stakeholders identify and prioritise countries with the best opportunities for implementation of an integrated prevention campaign (IPC) focused on diarrhoea, malaria and HIV prevention.
Design
Cross-sectional analysis of country-specific epidemiological data using an index tool developed for this purpose.
Setting
We calculated the total disability-adjusted life years (DALYs) attributed to diarrhoea, malaria and HIV for 214 World Bank economies. Criteria for inclusion were: low-income and middle-income countries, and total annual DALY burden in the top tertile (≥87 000 DALYs). 70 countries met inclusion criteria and were included in our opportunity analysis.
Outcome measures
We synthesised data on 10 indicators related to the potential reduction in burden and new coverage achievable by an IPC. We scored and ranked countries based on three summary opportunity metrics: DALYs per capita across the diseases, a composite score of tertile rankings of burden for each disease, and a score combining burden and intervention opportunity.
Results
We estimated the total annual global burden attributable to diarrhoea, malaria and HIV at 135 million DALYs. All of the countries with the highest opportunity for implementation of a diarrhoea, malaria and HIV IPC are in sub-Saharan Africa, regardless of opportunity metric used. Although the overall rank order changes, 16 countries rank among the top 23 highest opportunity countries for all three metrics.
Conclusions
Stakeholders can use this objective metric-based approach to prioritise countries for IPC scale-up. Priority countries are largely robust to the opportunity metric chosen.
doi:10.1136/bmjopen-2013-004308
PMCID: PMC3963065  PMID: 24647447
Epidemiology
21.  Measuring the burden of arboviral diseases: the spectrum of morbidity and mortality from four prevalent infections 
Background
Globally, arthropod-borne virus infections are increasingly common causes of severe febrile disease that can progress to long-term physical or cognitive impairment or result in early death. Because of the large populations at risk, it has been suggested that these outcomes represent a substantial health deficit not captured by current global disease burden assessments.
Methods
We reviewed newly available data on disease incidence and outcomes to critically evaluate the disease burden (as measured by disability-adjusted life years, or DALYs) caused by yellow fever virus (YFV), Japanese encephalitis virus (JEV), chikungunya virus (CHIKV), and Rift Valley fever virus (RVFV). We searched available literature and official reports on these viruses combined with the terms "outbreak(s)," "complication(s)," "disability," "quality of life," "DALY," and "QALY," focusing on reports since 2000. We screened 210 published studies, with 38 selected for inclusion. Data on average incidence, duration, age at onset, mortality, and severity of acute and chronic outcomes were used to create DALY estimates for 2005, using the approach of the current Global Burden of Disease framework.
Results
Given the limitations of available data, nondiscounted, unweighted DALYs attributable to YFV, JEV, CHIKV, and RVFV were estimated to fall between 300,000 and 5,000,000 for 2005. YFV was the most prevalent infection of the four viruses evaluated, although a higher proportion of the world's population lives in countries at risk for CHIKV and JEV. Early mortality and long-term, related chronic conditions provided the largest DALY components for each disease. The better known, short-term viral febrile syndromes caused by these viruses contributed relatively lower proportions of the overall DALY scores.
Conclusions
Limitations in health systems in endemic areas undoubtedly lead to underestimation of arbovirus incidence and related complications. However, improving diagnostics and better understanding of the late secondary results of infection now give a first approximation of the current disease burden from these widespread serious infections. Arbovirus control and prevention remains a high priority, both because of the current disease burden and the significant threat of the re-emergence of these viruses among much larger groups of susceptible populations.
doi:10.1186/1478-7954-9-1
PMCID: PMC3024945  PMID: 21219615
22.  HCV-related burden of disease in Europe: a systematic assessment of incidence, prevalence, morbidity, and mortality 
BMC Public Health  2009;9:34.
Background
Hepatitis C virus (HCV) is a leading cause of chronic liver disease, end-stage cirrhosis, and liver cancer, but little is known about the burden of disease caused by the virus. We summarised burden of disease data presently available for Europe, compared the data to current expert estimates, and identified areas in which better data are needed.
Methods
Literature and international health databases were systematically searched for HCV-specific burden of disease data, including incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and liver transplantation. Data were collected for the WHO European region with emphasis on 22 countries. If HCV-specific data were unavailable, these were calculated via HCV-attributable fractions.
Results
HCV-specific burden of disease data for Europe are scarce. Incidence data provided by national surveillance are not fully comparable and need to be standardised. HCV prevalence data are often inconclusive. According to available data, an estimated 7.3–8.8 million people (1.1–1.3%) are infected in our 22 focus countries. HCV-specific mortality, DALY, and transplantation data are unavailable. Estimations via HCV-attributable fractions indicate that HCV caused more than 86000 deaths and 1.2 million DALYs in the WHO European region in 2002. Most of the DALYs (95%) were accumulated by patients in preventable disease stages. About one-quarter of the liver transplants performed in 25 European countries in 2004 were attributable to HCV.
Conclusion
Our results indicate that hepatitis C is a major health problem and highlight the importance of timely antiviral treatment. However, data on the burden of disease of hepatitis C in Europe are scarce, outdated or inconclusive, which indicates that hepatitis C is still a neglected disease in many countries. What is needed are public awareness, co-ordinated action plans, and better data. European physicians should be aware that many infections are still undetected, provide timely testing and antiviral treatment, and avoid iatrogenic transmission.
doi:10.1186/1471-2458-9-34
PMCID: PMC2656539  PMID: 19161623
23.  Estimating the burden of rhodesiense sleeping sickness during an outbreak in Serere, eastern Uganda 
BMC Public Health  2008;8:96.
Background
Zoonotic sleeping sickness, or HAT (Human African Trypanosomiasis), caused by infection with Trypanosoma brucei rhodesiense, is an under-reported and neglected tropical disease. Previous assessments of the disease burden expressed as Disability-Adjusted Life Years (DALYs) for this infection have not distinguished T.b. rhodesiense from infection with the related, but clinically distinct Trypanosoma brucei gambiense form. T.b. rhodesiense occurs focally, and it is important to assess the burden at the scale at which resource-allocation decisions are made.
Methods
The burden of T.b. rhodesiense was estimated during an outbreak of HAT in Serere, Uganda. We identified the unique characteristics affecting the burden of rhodesiense HAT such as age, severity, level of under-reporting and duration of hospitalisation, and use field data and empirical estimates of these to model the burden imposed by this and other important diseases in this study population. While we modelled DALYs using standard methods, we also modelled uncertainty of our parameter estimates through a simulation approach. We distinguish between early and late stage HAT morbidity, and used disability weightings appropriate for the T.b. rhodesiense form of HAT. We also use a model of under-reporting of HAT to estimate the contribution of un-reported mortality to the overall disease burden in this community, and estimate the cost-effectiveness of hospital-based HAT control.
Results
Under-reporting accounts for 93% of the DALY estimate of rhodesiense HAT. The ratio of reported malaria cases to reported HAT cases in the same health unit was 133:1, however, the ratio of DALYs was 3:1. The age productive function curve had a close correspondence with the HAT case distribution, and HAT cases occupied more patient admission time in Serere during 1999 than all other infectious diseases other than malaria. The DALY estimate for HAT in Serere shows that the burden is much greater than might be expected from its relative incidence. Hospital based control in this setting appears to be highly cost-effective, highlighting the value of increasing coverage of therapy and reducing under-reporting.
Conclusion
We show the utility of calculating DALYs for neglected diseases at the local decision making level, and emphasise the importance of improved reporting systems for acquiring a better understanding of the burden of neglected zoonotic diseases.
doi:10.1186/1471-2458-8-96
PMCID: PMC2322978  PMID: 18366755
24.  Burden of traumatic spine fractures in Tehran, Iran 
BMC Public Health  2011;11:789.
Background
The Disability-Adjusted Life Year (DALY) was designed by the World Health Organization (WHO) to measure, compare, and analyze the burden of various diseases. To the best of our knowledge, this is the first study on the assessment of burden of traumatic spinal fracture (TSF) in an Iranian community. We estimated burden of TSF includes both isolated (iTSF) and associated injuries related to traumatic spinal fractures (aTSF) in Tehran, the capital of Iran, for the year 2006-2007 using DALYs.
Methods
Burden of TSF was estimated based on information provided by the national data on Iranian trauma, data from the WHO, and literature data using disease modeling (DISMOD). Incidence of TSF and associated injuries were obtained from two population based studies and National Trauma Data Bank in Iran, while duration, and relative risk of mortality (RRM) were obtained from WHO data and the literature. The incidence, duration, and relative risk of mortality (RRM) were used to calculate DALY for TSF. To calculate DALY, the years of life lost because of premature mortality (YLL) were added to the number of years lost because of disability (YLD). DALYs were calculated separately for both iTSF and aTSF. In-hospital YLD and post-hospital YLL for iTSF and in-hospital YLL and YLD were calculated for aTSFs.
Results
TSF incidence was 16.35 (95%CI: 3.4-48.0) per 100,000. The incidence of TSF in males was more than twice that of females. The largest DALYs were seen in 15-29 years. The highest burden of associated injuries of TSF was related to spinal cord and head injury. DALYs for aTSF were estimated to be 2496.9 years (32.0 DALY/100,000 population). The YLD and YLL were almost similar. Total DALY for iTSF and aTSF was 2568.9 years (32.92 DALY/100,000 population). Based on the risk extracted from the literature, post-hospital increased risk of mortality was increased by 1318 DALY (16.89 DALY/100,000 population).
Conclusion
This study showed a considerable burden for TSFs mainly due to associated injuries and increased lifelong RRM in patients with TSF.
doi:10.1186/1471-2458-11-789
PMCID: PMC3213027  PMID: 21988751
25.  The Global Epidemiology and Contribution of Cannabis Use and Dependence to the Global Burden of Disease: Results from the GBD 2010 Study 
PLoS ONE  2013;8(10):e76635.
Aims
Estimate the prevalence of cannabis dependence and its contribution to the global burden of disease.
Methods
Systematic reviews of epidemiological data on cannabis dependence (1990-2008) were conducted in line with PRISMA and meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Culling and data extraction followed protocols, with cross-checking and consistency checks. DisMod-MR, the latest version of generic disease modelling system, redesigned as a Bayesian meta-regression tool, imputed prevalence by age, year and sex for 187 countries and 21 regions. The disability weight associated with cannabis dependence was estimated through population surveys and multiplied by prevalence data to calculate the years of life lived with disability (YLDs) and disability-adjusted life years (DALYs). YLDs and DALYs attributed to regular cannabis use as a risk factor for schizophrenia were also estimated.
Results
There were an estimated 13.1 million cannabis dependent people globally in 2010 (point prevalence0.19% (95% uncertainty: 0.17-0.21%)). Prevalence peaked between 20-24 yrs, was higher in males (0.23% (0.2-0.27%)) than females (0.14% (0.12-0.16%)) and in high income regions. Cannabis dependence accounted for 2 million DALYs globally (0.08%; 0.05-0.12%) in 2010; a 22% increase in crude DALYs since 1990 largely due to population growth. Countries with statistically higher age-standardised DALY rates included the United States, Canada, Australia, New Zealand and Western European countries such as the United Kingdom; those with lower DALY rates were from Sub-Saharan Africa-West and Latin America. Regular cannabis use as a risk factor for schizophrenia accounted for an estimated 7,000 DALYs globally.
Conclusion
Cannabis dependence is a disorder primarily experienced by young adults, especially in higher income countries. It has not been shown to increase mortality as opioid and other forms of illicit drug dependence do. Our estimates suggest that cannabis use as a risk factor for schizophrenia is not a major contributor to population-level disease burden.
doi:10.1371/journal.pone.0076635
PMCID: PMC3811989  PMID: 24204649

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