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1.  Economic Impact of Cystic Echinococcosis in Peru 
Background
Cystic echinococcosis (CE) constitutes an important public health problem in Peru. However, no studies have attempted to estimate the monetary and non-monetary impact of CE in Peruvian society.
Methods
We used official and published sources of epidemiological and economic information to estimate direct and indirect costs associated with livestock production losses and human disease in addition to surgical CE-associated disability adjusted life years (DALYs) lost.
Findings
The total estimated cost of human CE in Peru was U.S.$2,420,348 (95% CI:1,118,384–4,812,722) per year. Total estimated livestock-associated costs due to CE ranged from U.S.$196,681 (95% CI:141,641–251,629) if only direct losses (i.e., cattle and sheep liver destruction) were taken into consideration to U.S.$3,846,754 (95% CI:2,676,181–4,911,383) if additional production losses (liver condemnation, decreased carcass weight, wool losses, decreased milk production) were accounted for. An estimated 1,139 (95% CI: 861–1,489) DALYs were also lost due to surgical cases of CE.
Conclusions
This preliminary and conservative assessment of the socio-economic impact of CE on Peru, which is based largely on official sources of information, very likely underestimates the true extent of the problem. Nevertheless, these estimates illustrate the negative economic impact of CE in Peru.
Author Summary
Cystic echinococcosis (CE), caused by infection with the larval stage of the cestode Echinococcus granulosus, constitutes an important public health problem in Peru. Despite its high prevalence in endemic communities no studies have attempted to estimate the economic impact of CE in Peruvian society. We used official and published sources of epidemiological and economic information to estimate direct and indirect costs associated with livestock production losses and human disease. We also used disability adjusted life years (DALYs) which is an overall measure of disease burden, expressed as number of years lost due to ill-health, disability or early death due to CE. We found that the total estimated cost of human CE in Peru was U.S.$2,420,348 per year. Total estimated livestock-associated costs due to CE ranged from U.S.$196,681 to U.S.$3,846,754. An estimated 1,139 DALYs were also lost due to surgical cases of CE which is comparable to DALY losses from Amebiasis or Malaria in Peru. This conservative assessment found significant economic losses caused by this CE in Peruvian society. The findings of this study are important as these data can serve to prioritize those areas that may need to be targeted in a control program.
doi:10.1371/journal.pntd.0001179
PMCID: PMC3101191  PMID: 21629731
2.  The Monetary Burden of Cystic Echinococcosis in Iran 
Cystic echinococcosis (CE) is a globally distributed parasitic infection of humans and livestock. The disease is of significant medical and economic importance in many developing countries, including Iran. However, the socioeconomic impact of the disease, in most endemic countries, is not fully understood. The purpose of the present study was to determine the monetary burden of CE in Iran. Epidemiological data, including prevalence and incidence of CE in humans and animals, were obtained from regional hospitals, the scientific literature, and official government reports. Economic data relating to human and animal disease, including cost of treatment, productivity losses, and livestock production losses were obtained from official national and international datasets. Monte Carlo simulation methods were used to represent uncertainty in input parameters. Mean number of surgical CE cases per year for 2000–2009 was estimated at 1,295. The number of asymptomatic individuals living in the country was estimated at 635,232 (95% Credible Interval, CI 149,466–1,120,998). The overall annual cost of CE in Iran was estimated at US$232.3 million (95% CI US$103.1–397.8 million), including both direct and indirect costs. The cost associated with human CE was estimated at US$93.39 million (95% CI US$6.1–222.7 million) and the annual cost associated with CE in livestock was estimated at US$132 million (95% CI US$61.8–246.5 million). The cost per surgical human case was estimated at US$1,539. CE has a considerable economic impact on Iran, with the cost of the disease approximated at 0.03% of the country's gross domestic product. Establishment of a CE surveillance system and implementation of a control program are necessary to reduce the economic burden of CE on the country. Cost-benefit analysis of different control programs is recommended, incorporating present knowledge of the economic losses due to CE in Iran.
Author Summary
Cystic echinococcosis (CE), caused by the tapeworm Echinococcus granulosus, is a zoonotic infection that occurs worldwide. The adult parasite resides in the small intestines of dogs and the cyst form can develop in the liver and lungs of both humans and livestock. CE causes medical, veterinary, and economic losses in endemic areas. However, data on the economic consequences of CE are lacking. The present study estimated the monetary burden of CE in Iran. We used epidemiological and economic information to estimate direct and indirect costs of human and livestock CE in the country. Costs associated with human CE included the costs of surgery and hospital services in addition to lost wages due to work absenteeism during hospitalization and recovery. Costs associated with CE in livestock included losses due to condemnation of livers and lungs during carcass inspections, decreased carcass weight, reproductive losses, and reductions in milk and other animal products. We estimated the overall annual cost of CE in Iran at US$232.25 million, with the cost of the disease estimated to be approximately 0.03% of the country's gross domestic product. Implementation of a control program is necessary to reduce the economic burden of CE on Iran.
doi:10.1371/journal.pntd.0001915
PMCID: PMC3510083  PMID: 23209857
3.  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
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.  Cystic Echinococcosis in the Province of Álava, North Spain: The Monetary Burden of a Disease No Longer under Surveillance 
Cystic echinococcosis (CE) is endemic in Spain but has been considered non-endemic in the province of Álava, Northern Spain, since 1997. However, Álava is surrounded by autonomous regions with some of the highest CE prevalence proportions in the nation, casting doubts about the current classification. The purpose of this study is to estimate the frequency of CE in humans and animals and to use this data to determine the societal cost incurred due to CE in the Álava population in 2005. We have identified epidemiological and clinical data from surveillance and hospital records, prevalence data in intermediate (sheep and cattle) host species from abattoir records, and economical data from national and regional official institutions. Direct costs (diagnosis, treatment, medical care in humans and condemnation of offal in livestock species) and indirect costs (productivity losses in humans and reduction in growth, fecundity and milk production in livestock) were modelled using the Latin hypercube method under five different scenarios reflecting different assumptions regarding the prevalence of asymptomatic cases and associated productivity losses in humans. A total of 13 human CE cases were reported in 2005. The median total cost (95% credible interval) of CE in humans and animals in Álava in 2005 was estimated to range between €61,864 (95%CI%: €47,304–€76,590) and €360,466 (95%CI: €76,424–€752,469), with human-associated losses ranging from 57% to 93% of the total losses, depending on the scenario used. Our data provide evidence that CE is still very well present in Álava and incurs important cost to the province every year. We expect this information to prove valuable for public health agencies and policy-makers, as it seems advisable to reinstate appropriate surveillance and monitoring systems and to implement effective control measures that avoid the spread and recrudescence of the disease.
Author Summary
Historically, cystic echinococcosis (CE) is one of the most important zoonotic diseases in Spain. The initiation of a number of control campaigns in the second half of the 1980s has led to a substantial reduction of the number of CE infections both in humans and livestock species. As a consequence of this initial success, obligation to report human CE cases was revoked in 1997 in a number of Spanish autonomous regions that were consequently considered non-endemic for CE. This policy has not been translated to livestock species, where the identification of hydatid cysts and the reporting of prevalence data remain compulsory in all national slaughterhouses. We present here an estimation of the human and animal CE associated monetary losses in the province of Álava, North Spain, for the year 2005. Obtained economic data corroborate the epidemiological findings and demonstrate that CE has important socio-economic consequences in Álava. Taking together, our data suggest that surveillance status of CE in Álava (and very likely in other Spanish regions currently classified as non-endemic areas) should be reassessed. The situation also indicates that more accurate and effective methods for detecting and reporting the disease at the regional and national level are greatly needed.
doi:10.1371/journal.pntd.0003069
PMCID: PMC4125306  PMID: 25102173
6.  The Global Burden of Alveolar Echinococcosis 
Background
Human alveolar echinococcosis (AE) is known to be common in certain rural communities in China whilst it is generally rare and sporadic elsewhere. The objective of this study was to provide a first estimate of the global incidence of this disease by country. The second objective was to estimate the global disease burden using age and gender stratified incidences and estimated life expectancy with the disease from previous results of survival analysis. Disability weights were suggested from previous burden studies on echinococcosis.
Methodology/Principal Findings
We undertook a detailed review of published literature and data from other sources. We were unable to make a standardised systematic review as the quality of the data was highly variable from different countries and hence if we had used uniform inclusion criteria many endemic areas lacking data would not have been included. Therefore we used evidence based stochastic techniques to model uncertainty and other modelling and estimating techniques, particularly in regions where data quality was poor. We were able to make an estimate of the annual global incidence of disease and annual disease burden using standard techniques for calculation of DALYs. Our studies suggest that there are approximately 18,235 (CIs 11,900–28,200) new cases of AE per annum globally with 16,629 (91%) occurring in China and 1,606 outside China. Most of these cases are in regions where there is little treatment available and therefore will be fatal cases. Based on using disability weights for hepatic carcinoma and estimated age and gender specific incidence we were able to calculate that AE results in a median of 666,434 DALYs per annum (CIs 331,000-1.3 million).
Conclusions/Significance
The global burden of AE is comparable to several diseases in the neglected tropical disease cluster and is likely to be one of the most important diseases in certain communities in rural China on the Tibetan plateau.
Author Summary
Human alveolar echinococcosis (AE), caused by the larval stage of the fox tapeworm Echinococcus multilocularis, is amongst the world's most dangerous zoonoses. Transmission to humans is by consumption of parasite eggs which are excreted in the faeces of the definitive hosts: foxes and, increasingly, dogs. Transmission can be through contact with the definitive host or indirectly through contamination of food or possibly water with parasite eggs. We made an intensive search of English, Russian, Chinese and other language databases. We targeted data which could give country specific incidence or prevalence of disease and searched for data from every country we believed to be endemic for AE. We also used data from other sources (often unpublished). From this information we were able to make an estimate of the annual global incidence of disease and disease burden using standard techniques for calculation of DALYs. Our studies suggest that AE results in a median of 18,235 cases globally with a burden of 666,433 DALYs per annum. This is the first estimate of the global burden of AE both in terms of global incidence and DALYs and demonstrates the burden of AE is comparable to several diseases in the neglected tropical disease cluster.
doi:10.1371/journal.pntd.0000722
PMCID: PMC2889826  PMID: 20582310
7.  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
8.  Priorities for research and control of cestode zoonoses in Asia 
Globally, cestode zoonoses cause serious public health problems, particularly in Asia. Among all neglected zoonotic diseases, cestode zoonoses account for over 75% of global disability adjusted life years (DALYs) lost. An international symposium on cestode zoonoses research and control was held in Shanghai, China between 28th and 30th October 2012 in order to establish joint efforts to study and research effective approaches to control these zoonoses. It brought together 96 scientists from the Asian region and beyond to exchange ideas, report on progress, make a gap analysis, and distill prioritizing settings with a focus on the Asian region. Key objectives of this international symposium were to agree on solutions to accelerate progress towards decreasing transmission, and human mortality and morbidity caused by the three major cestode zoonoses (cystic echinococcosis, alveolar echinococcosis, and cysticercosis); to critically assess the potential to control these diseases; to establish a research and validation agenda on existing and new approaches; and to report on novel tools for the study and control of cestode zoonoses.
doi:10.1186/2049-9957-2-16
PMCID: PMC3750256  PMID: 23915395
Neglected diseases; Cestode zoonoses; Asia; Priority; Gap; Research; Control
9.  Echinococcus granulosus Infection and Options for Control of Cystic Echinococcosis in Tibetan Communities of Western Sichuan Province, China 
Background
Human cystic echinococcosis (CE) is highly endemic in the Tibetan regions of Sichuan where most families keep guard dogs and where there are considerable numbers of ownerless/stray dogs. Strong Buddhist beliefs do not allow for elimination of stray dogs, and many strays are actually fed and adopted by households or monasteries. On account of the high altitude (3900–5000 m), pasturage is the major agricultural activity in this area. The harsh mountainous climate often leads to many grazing animals dying on the pasture at the end of a hard winter. The skin and some meat are taken, and the rest of the animal is left for scavenging birds and animals. The poor sanitation and hygiene, the Buddhist doctrine of allowing old livestock to die naturally, plus the unrestricted disposal of animal viscera post-slaughter may be responsible for the high prevalence of human CE in this setting.
Methods and Findings
As part of a large collaborative control program for CE in Ganzi County, situated in the west of Sichuan Province, surveillance for Echinococcus infection in domestic dogs using a coproantigen method and necropsy of unwanted dogs was carried out prior to (in 2000) and after (in 2005) dog anthelminthic treatment (5 mg/kg oral praziquantal at 6 month intervals) to determine the efficacy of the treatment for control. The prevalence of E. granulosus only in dogs by necropsy was 27% and 22%, and prevalence of both Echinococcus spp. by necropsy was 63% and 38%; prevalence of both Echinococcus spp. by coproantigen analysis was 50% and 17%. Necropsy of sheep/goats (age <1 to 12 years) (prevalence of E. granulosus in 1–6-year-old animals was 38% and in 10–12-year-old animals was 70%) and yaks (age 4 years) (prevalence of E. granulosus was 38%) was undertaken to determine the baseline transmission pressure. Protoscoleces were only found in very old sheep/goats and yaks. Necropsy of dogs in the Datangma district indicated that there was no apparent significant change in the overall prevalence of E. granulosus in unwanted dogs after 5 years of 6-month praziquantel treatment. However, this was likely due to the number of dogs available for necropsy being too small to reflect the real situation prevailing. There was a highly significant decrease in Echinococcus prevalence after the 5-year treatment program shown by coproantigen-ELISA. This indicated a decreasing but continuing risk for re-infection of domestic and stray dogs. Genotyping of E. granulosus samples obtained from necropsied sheep/goats and yaks and from locally infected humans at surgery was carried out to determine the strain of parasite responsible for human infection. DNA genotyping indicated that only the sheep strain (G1) of E. granulosus was present in the study area.
Conclusions
Considerable re-infection rates of E. granulosus among dogs indicated a high infection pressure from infected livestock in this region, most likely from older animals dying on the pasture. A combination of livestock vaccination with the Eg95 vaccine, which is effective against the sheep strain of E. granulosus, and dog anthelmintic treatment, thus targeting two critical points of the parasite life-cycle, would avoid the conflicts of religion or local culture and could achieve the goal of hydatid control in the long term.
Author Summary
Human cystic echinococcosis (CE) is highly endemic in Tibetan regions of Sichuan. As part of a control program for CE in Datangma district, Ganzi County, necropsy of strays and coproantigen-ELISA of all dogs was carried out prior to and post-drug treatment to determine the efficacy of the treatment for control. Examination of sheep/goats and yaks was undertaken to determine the baseline transmission pressure to dogs. The necropsy results indicated no apparent significant change in the overall prevalence of E. granulosus in unwanted dogs after 5 years of 6-month treatment. In contrast, there was a highly significant decrease in Echinococcus prevalence in domestic/stray dogs after the 5-year treatment program shown by coproantigen-ELISA. This indicated a decreasing but continuing risk for re-infection of dogs resulting from high infection pressure from the numerous infected domestic animals. DNA genotyping indicated the presence only of the sheep strain (G1) of E. granulosus in the study area. A combination of livestock vaccination with the highly effective Eg95 vaccine and dog drug treatment, targeting two critical points of the parasite life-cycle, would avoid the conflicts of religion or local culture and achieve the goal of hydatid control in the long term in the area.
doi:10.1371/journal.pntd.0000426
PMCID: PMC2668793  PMID: 19399162
10.  Human and Canine Echinococcosis Infection in Informal, Unlicensed Abattoirs in Lima, Peru 
Echinococcus granulosus infections are a major public health problem in livestock-raising regions around the world. The life cycle of this tapeworm is sustained between dogs (definitive host, canine echinococcosis), and herbivores (intermediary host, cystic hydatid disease). Humans may also develop cystic hydatid disease. Echinococcosis is endemic in rural areas of Peru; nevertheless, its presence or the extension of the problem in urban areas is basically unknown. Migration into Lima, an 8-million habitant's metropolis, creates peripheral areas where animals brought from endemic areas are slaughtered without veterinary supervision. We identified eight informal, unlicensed abattoirs in a peripheral district of Lima and performed a cross-sectional study in to assess the prevalence of canine echinococcosis, evaluated by coproELISA followed by PCR evaluation and arecoline purge. Eight of 22 dogs (36%) were positive to coproELISA, and four (18%) were confirmed to be infected with E. granulosus tapeworms either by PCR or direct observation (purge). Later evaluation of the human population living in these abattoirs using abdominal ultrasound, chest X-rays and serology, found 3 out of 32 (9.3%) subjects with echinococcal cysts in the liver (two viable, one calcified), one of whom had also lung involvement and a strongly positive antibody response. Autochthonous transmission of E. granulosus is present in Lima. Informal, unlicensed abattoirs may be sources of infection to neighbouring people in this urban environment.
Author Summary
Echinococcus granulosus infections are a major public health problem in livestock-raising regions around the world. This parasite is transmitted by dogs, and humans could be accidentally infected, developing cystic lesions in internal organs after several years of infection. The risk of infection has been widely described in Peruvian rural areas; nevertheless the extension of the problem in urban areas is basically unknown. Migration into Lima, an 8-million habitant's metropolis, creates peripheral areas where animals brought from endemic areas are slaughtered without veterinary supervision. In our study, we assess the number of infected dogs, which were living in eight informal, unlicensed abattoirs in a peripheral district of Lima, by evaluation of dog faeces using different techniques. We identified that 4 of 22 dogs were infected with E. granulosus worm. Later evaluation of the human population living in these abattoirs using abdominal ultrasound, chest X-rays and serology, found 3 of 32 subjects had echinococcal cysts in the liver, one of whom had also a cyst in lung and a positive serological test. This work demonstrates that autochthonous transmission of E. granulosus is present in Lima and that informal, unlicensed abattoirs may be sources of infection to neighbouring people in this urban environment.
doi:10.1371/journal.pntd.0001462
PMCID: PMC3317905  PMID: 22509413
11.  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
12.  Widespread co-endemicity of human cystic and alveolar echinococcosis on the eastern Tibetan Plateau, northwest Sichuan/southeast Qinghai, China 
Acta tropica  2009;113(3):248-256.
Cystic echinococcosis (CE) or hydatid disease is known to be cosmopolitan in its global distribution, while alveolar echinococcosis (AE) is a much rarer though more pathogenic hepatic parasitic disease restricted to the northern hemisphere. Both forms of human echinococcosis are known to occur on the Tibetan Plateau, but the epidemiological characteristics remain poorly understood. In our current study, abdominal ultrasound screening programs for echinococcosis were conducted in thirty-one Tibetan townships in Ganze and Aba Tibetan Autonomous Prefectures of northwest Sichuan Province during 2001-2008. Hospital records (1992-2006) in a major regional treatment centre for echinococcosis in Sichuan Province were also reviewed. Of 10,186 local residents examined by portable ultrasound scan, 645 (6.3%) were diagnosed with echinococcosis: a prevalence of 3.2% for CE, 3.1% for AE and 0.04% for dual infection (both CE and AE). Human cystic and alveolar echinococcosis in pastoral areas was highly co-endemic, in comparison to much lower prevalences in semi-pastoral or farming regions. The high ultrasound prevalence in these co-endemic areas in northwest Sichuan Province was also reflected in the hospital study, and hospital records furthermore indicated another possible highly co-endemic focus in Guoluo Prefecture of Qinghai Province, located at the border of northwest Sichuan. These chronic cestode zoonoses constitute an unparalleled major public health problem for pastoral Tibetan communities, and pose great difficulties for adequate treatment access and effective transmission control in such remote regions.
doi:10.1016/j.actatropica.2009.11.006
PMCID: PMC2847145  PMID: 19941830
Cystic echinococcosis; Alveolar echinococcosis; Ultrasound; Prevalence; Tibetan; Sichuan Province; Qinghai Province
13.  Evaluation of Oxfendazole, Praziquantel and Albendazole against Cystic Echinococcosis: A Randomized Clinical Trial in Naturally Infected Sheep 
Background
Cystic Echinococosis (CE) is a zoonotic disease caused by larval stage Echinococcus granulosus. We determined the effects of high dose of Oxfendazole (OXF), combination Oxfendazole/Praziquantel (PZQ), and combination Albendazole (ABZ)/Praziquantel against CE in sheep.
Methodology/Principal Findings
A randomized placebo-controlled trial was carried out on 118 randomly selected ewes. They were randomly assigned to one of the following groups: 1) placebo; 2) OXF 60 mg/Kg of body weight (BW) weekly for four weeks; 3) ABZ 30 mg/Kg BW + PZQ 40 mg/Kg BW weekly for 6 weeks, and 4) OXF 30 mg/Kg BW+ PZQ 40 mg/Kg BW biweekly for 3 administrations (6 weeks). Percent protoscolex (PSC) viability was evaluated using a 0.1% aqueous eosin vital stain for each cyst. “Noninfective” sheep were those that had no viable PSCs; “low-medium infective” were those that had 1% to 60% PSC viability; and “high infective” were those with more than 60% PSC viability. We evaluated 92 of the 118 sheep. ABZ/PZQ led the lowest PSC viability for lung cysts (12.7%), while OXF/PZQ did so for liver cysts (13.5%). The percentage of either “noninfective” or “low-medium infective” sheep was 90%, 93.8% and 88.9% for OXF, ABZ/PZQ and OXF/PZQ group as compared to 50% “noninfective” or “low-medium infective” for placebo. After performing all necropsies, CE prevalence in the flock of sheep was 95.7% (88/92) with a total number of 1094 cysts (12.4 cysts/animal). On average, the two-drug-combination groups resulted pulmonary cysts that were 6 mm smaller and hepatic cysts that were 4.2 mm smaller than placebo (p<0.05).
Conclusions/Significance
We demonstrate that Oxfendazole at 60 mg, combination Oxfendazole/Praziquantel and combination Albendazole/Praziquantel are successful schemas that can be added to control measures in animals and merits further study for the treatment of animal CE. Further investigations on different schedules of monotherapy or combined chemotherapy are needed, as well as studies to evaluate the safety and efficacy of Oxfendazole in humans.
Author Summary
Cystic Echinococcosis (CE) is a near-cosmopolitan parasitic zoonosis that causes economic losses in many regions of the world. This parasitic infection can be regarded as an emerging or re-emerging disease causing considerable losses in livestock production. CE is produced by the larval cystic stage (hydatid) of the dog parasite Echinococcus granulosus. After infective eggs are ingested, cysts develop mainly in lungs and liver of humans and animals (sheep, cattle, pigs, horses, etc). Infected people may require surgery and/or Albendazole-based chemotherapy. In this study, we evaluated the effects of Oxfendazole alone (an antiparasitic drug used in animals), Oxfendazole plus Praziquantel, and Albendazole plus Praziquantel against hydatid cysts in sheep over 4 to 6 weeks of treatment. All of the treatments in this study were efficacious in killing the larval stages and, therefore, in minimizing the risk of a dog acquiring new infections (taenias). These treatment schemes can be added to control measures in animals and eventually could be used for the treatment of human infection. Further investigations on different schedules of monotherapy or combined chemotherapy are needed, as well as studies to evaluate the safety and efficacy of Oxfendazole in humans.
doi:10.1371/journal.pntd.0000616
PMCID: PMC2826409  PMID: 20186332
14.  Human Echinococcosis Mortality in the United States, 1990–2007 
Background
Despite the endemic nature of Echinococcus granulosus and Echinococcus multilocularis infection in regions of the United States (US), there is a lack of data on echinococcosis-related mortality. To measure echinococcosis-associated mortality in the US and assess possible racial/ethnic disparities, we reviewed national-death certificate data for an 18-year period.
Methodology/Principal Findings
Echinococcosis-associated deaths from 1990 through 2007 were identified from multiple-cause-coded death records and were combined with US census data to calculate mortality rates. A total of 41 echinococcosis-associated deaths occurred over the 18-year study period. Mortality rates were highest in males, Native Americans, Asians/Pacific Islanders, Hispanics and persons 75 years of age and older. Almost a quarter of fatal echinococcosis-related cases occurred in residents of California. Foreign-born persons accounted for the majority of echinococcosis-related deaths; however, both of the fatalities in Native Americans and almost half of the deaths in whites were among US-born individuals.
Conclusions/Significance
Although uncommon, echinococcosis-related deaths occur in the US. Clinicians should be aware of the diagnosis, particularly in foreign-born patients from Echinococcus endemic areas, and should consider tropical infectious disease consultation early.
Author Summary
Human echinococcosis is a parasitic disease that affects an estimated 2–3 million people and results in an annual monetary loss of over $750,000,000 worldwide. It results in the development of life threatening tissue cysts, primarily in the liver and lung, following accidental ingestion of eggs in infected dog, fox or wild canine feces. Echinococcus parasites have a complex, two-host lifecycle (such as in dogs and sheep) in which humans are an aberrant, dead-end host. The vast majority of cases of human echinococcosis occur outside of the United States (US); however, cases within the US do occur. In this study, the authors examined death certificate data of US residents from 1990–2007 in which echinococcosis was listed as one of the diagnoses at death. The analysis demonstrated 41 echinococcosis-related deaths over the 18-year study period with foreign-born persons accounting for the majority of the deaths. This study helps quantify echinococcosis deaths among US residents and adds further support to the importance of funding echinococcosis prevention research.
doi:10.1371/journal.pntd.0001524
PMCID: PMC3274497  PMID: 22347516
15.  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
16.  An Oral Recombinant Vaccine in Dogs against Echinococcus granulosus, the Causative Agent of Human Hydatid Disease: A Pilot Study 
Dogs are the main source of human cystic echinococcosis. An oral vaccine would be an important contribution to control programs in endemic countries. We conducted two parallel experimental trials in Morocco and Tunisia of a new oral vaccine candidate against Echinococcus granulosus in 28 dogs. The vaccine was prepared using two recombinant proteins from adult worms, a tropomyosin (EgTrp) and a fibrillar protein similar to paramyosin (EgA31), cloned and expressed in a live attenuated strain of Salmonella enterica serovar typhimurium.
In each country, five dogs were vaccinated with the associated EgA31 and EgTrp; three dogs received only the vector Salmonella; and six dogs were used as different controls. The vaccinated dogs received two oral doses of the vaccine 21 d apart, and were challenged 20 d later with 75,000 living protoscoleces. The controls were challenged under the same conditions. All dogs were sacrificed 26–29 d postchallenge, before the appearance of eggs, for safety reasons.
We studied the histological responses to both the vaccine and control at the level of the duodenum, the natural localization of the cestode. Here we show a significant decrease of parasite burden in vaccinated dogs (70% to 80%) and a slower development rate in all remaining worms. The Salmonella vaccine EgA31-EgTrp demonstrated a high efficacy against E. granulosus promoting its potential role in reducing transmission to humans and animals.
Author Summary
In many countries in the world, livestock and humans are affected with hydatid disease, which is caused by the development, in the viscera, of the larval stage of the cestode Echinococcus granulosus. They become infected by ingesting the eggs of this parasite, which are passed in the feces of the dog—the host of the adult worm. Domestic dogs are key in the transmission to livestock and humans.
This disease remains a major economic and public health problem in affected countries. Because dogs are quickly reinfected, control programs in these locations include monthly anthelmintic deworming. These control measures, however, are burdensome for the owner, so they often fail. In contrast, vaccination can take place in control programs at different stages of the parasite life cycle. For example, currently an effective recombinant vaccine for sheep has been developed that should work indirectly to reduce infection in dogs, which tend to eat sheep offal. However, we propose that a recombinant oral vaccine given to the small number of dogs keeping the herd would decrease the number of Echinococcus granulosus adult worms and, consequently, the number of infective eggs. This measure would help reduce the contamination risk factors for humans and livestock, and would be cost-effective for the owners of the dogs.
doi:10.1371/journal.pntd.0000125
PMCID: PMC2217674  PMID: 18235847
17.  Epidemiological Studies on Echinococcosis and Characterization of Human and Livestock Hydatid Cysts in Mauritania 
Background
Echinococcosis/hydatidosis is considered endemic in Mauritania. The aim of this study is to present an epidemiological study on the echinococcosis in man and animals in the Nouakchott region.
Methods
The internal organs from livestock carcasses were inspected for research of hydatid cysts. The hydatid fluid was examined for research of the protoscoleces. Dogs were necropsied for the collect of Echinococcus granulosus.
Results
In the Nouakchott Hospital, 24 surgical operation of human hydatid cysts have been performed, out of which 50% were localised in the lung, 33% in the liver and 17% elsewhere. Then, the incidence rate would be of 1.2% per 100 000 inhabitants in Mauritania. In the dog, the prevalence rate is 14%. The average number of E. granulosus on the whole dogs is 172 and 1227 on the positive dogs. Concerning the livestock, hydatid cysts found in 30.1% of the dromedary, 5.5% of the cattle and 6.5 of the sheep. The fertility rate of hydatid cysts in humans (75%) and camels (76%) was significantly higher than that of sheep (24%) and cattle (23%) (P<0.0001). Hydatid infestation is characterized globally by the dominance of pulmonary localizations in humans (50%) and camels (72.7%) and in the liver in sheep (76.1%) and cattle (82.3%).
Conclusion
The differences between prevalence rates, the fertility of hydatid cysts and diversity sites localization observed in humans and camels of one hand and the sheep and cattle on the other hand, depends possibly the strain(s) diversity of E. granulosus.
PMCID: PMC3279863  PMID: 22347274
Prevalence; Hydatidosis; Echinococcosis; Mauritania
18.  Clinical Manifestations of Human Brucellosis: A Systematic Review and Meta-Analysis 
Background
The objectives of this systematic review, commissioned by WHO, were to assess the frequency and severity of clinical manifestations of human brucellosis, in view of specifying a disability weight for a DALY calculation.
Methods/Principal Findings
Thirty three databases were searched, with 2,385 articles published between January 1990–June 2010 identified as relating to human brucellosis. Fifty-seven studies were of sufficient quality for data extraction. Pooled proportions of cases with specific clinical manifestations were stratified by age category and sex and analysed using generalized linear mixed models. Data relating to duration of illness and risk factors were also extracted. Severe complications of brucellosis infection were not rare, with 1 case of endocarditis and 4 neurological cases per 100 patients. One in 10 men suffered from epididymo-orchitis. Debilitating conditions such as arthralgia, myalgia and back pain affected around half of the patients (65%, 47% and 45%, respectively). Given that 78% patients had fever, brucellosis poses a diagnostic challenge in malaria-endemic areas. Significant delays in appropriate diagnosis and treatment were the result of health service inadequacies and socioeconomic factors. Based on disability weights from the 2004 Global Burden of Disease Study, a disability weight of 0.150 is proposed as the first informed estimate for chronic, localised brucellosis and 0.190 for acute brucellosis.
Conclusions
This systematic review adds to the understanding of the global burden of brucellosis, one of the most common zoonoses worldwide. The severe, debilitating, and chronic impact of brucellosis is highlighted. Well designed epidemiological studies from regions lacking in data would allow a more complete understanding of the clinical manifestations of disease and exposure risks, and provide further evidence for policy-makers. As this is the first informed estimate of a disability weight for brucellosis, there is a need for further debate amongst brucellosis experts and a consensus to be reached.
Author Summary
Brucellosis is a bacterial disease transmitted to humans by consumption of infected, unpasteurised animal milk or through direct contact with infected animals, particularly aborted foetuses. The livestock production losses resulting from these abortions have a major economic impact on individuals and communities. Infected people often suffer from a chronic, debilitating illness. This systematic review on the symptoms of human brucellosis is the first ever conducted. Using strict exclusion criteria, 57 scientific articles published between January 1990–June 2010 which included high quality data were identified. Severe complications of brucellosis infection were not rare, with 1 case of endocarditis and 4 neurological cases per 100 patients. One in 10 men suffered from testicular infection, which can case sterility. Debilitating conditions such as joint, muscle, and back pain affected around half of the patients. Given that most patients had fever, brucellosis poses a diagnostic challenge in malaria-endemic areas where fever is often assumed to be malaria. More high quality data is needed for a more complete understanding of the clinical manifestations of disease and exposure risks, and to provide further evidence for policy-makers.
doi:10.1371/journal.pntd.0001929
PMCID: PMC3516581  PMID: 23236528
19.  Global Burden of Human Brucellosis: A Systematic Review of Disease Frequency 
Background
This report presents a systematic review of scientific literature published between 1990–2010 relating to the frequency of human brucellosis, commissioned by WHO. The objectives were to identify high quality disease incidence data to complement existing knowledge of the global disease burden and, ultimately, to contribute towards the calculation of a Disability-Adjusted Life Years (DALY) estimate for brucellosis.
Methods/Principal Findings
Thirty three databases were searched, identifying 2,385 articles relating to human brucellosis. Based on strict screening criteria, 60 studies were selected for quality assessment, of which only 29 were of sufficient quality for data analysis. Data were only available from 15 countries in the regions of Northern Africa and Middle East, Western Europe, Central and South America, Sub-Saharan Africa, and Central Asia. Half of the studies presented incidence data, six of which were longitudinal prospective studies, and half presented seroprevalence data which were converted to incidence rates. Brucellosis incidence varied widely between, and within, countries. Although study biases cannot be ruled out, demographic, occupational, and socioeconomic factors likely play a role. Aggregated data at national or regional levels do not capture these complexities of disease dynamics and, consequently, at-risk populations or areas may be overlooked. In many brucellosis-endemic countries, health systems are weak and passively-acquired official data underestimate the true disease burden.
Conclusions
High quality research is essential for an accurate assessment of disease burden, particularly in Eastern Europe, the Asia-Pacific, Central and South America and Africa where data are lacking. Providing formal epidemiological and statistical training to researchers is essential for improving study quality. An integrated approach to disease surveillance involving both human health and veterinary services would allow a better understanding of disease dynamics at the animal-human interface, as well as a more cost-effective utilisation of resources.
Author Summary
Brucellosis is a bacterial disease transmitted to humans by consumption of infected, unpasteurised animal milk or through direct contact with infected animals, particularly aborted foetuses. The livestock production losses resulting from these abortions have a major economic impact on individuals and communities. Infected people often suffer from a chronic, debilitating illness. This systematic review of the incidence of human brucellosis is the first ever conducted. Using strict exclusion criteria, 28 scientific articles published between January 1990–June 2010 which included high quality data were identified. Half of these studies presented incidence data and half presented seroprevalence data which were converted to incidence rates. Data were only available from 15 countries in the regions of Northern Africa and Middle East, Western Europe, Central and South America, Sub-Saharan Africa and Central Asia. Brucellosis incidence varied widely between and within countries. Demographic, occupational and socioeconomic factors may play a role in these differences. In many brucellosis-endemic countries, health systems are weak, and official data are likely to underestimate the true disease burden. High quality research is needed, particularly from Eastern Europe, the Asia-Pacific, Central and South America and Africa. An integrated approach to disease surveillance involving both human health and veterinary services would allow a better understanding of the disease, as well as a more cost-effective utilisation of resources.
doi:10.1371/journal.pntd.0001865
PMCID: PMC3493380  PMID: 23145195
20.  Systematic review of general burden of disease studies using disability-adjusted life years 
Objective
To systematically review the methodology of general burden of disease studies. Three key questions were addressed: 1) what was the quality of the data, 2) which methodological choices were made to calculate disability adjusted life years (DALYs), and 3) were uncertainty and risk factor analyses performed? Furthermore, DALY outcomes of the included studies were compared.
Methods
Burden of disease studies (1990 to 2011) in international peer-reviewed journals and in grey literature were identified with main inclusion criteria being multiple-cause studies that quantified the burden of disease as the sum of the burden of all distinct diseases expressed in DALYs. Electronic database searches included Medline (PubMed), EMBASE, and Web of Science. Studies were collated by study population, design, methods used to measure mortality and morbidity, risk factor analyses, and evaluation of results.
Results
Thirty-one studies met the inclusion criteria of our review. Overall, studies followed the Global Burden of Disease (GBD) approach. However, considerable variation existed in disability weights, discounting, age-weighting, and adjustments for uncertainty. Few studies reported whether mortality data were corrected for missing data or underreporting. Comparison with the GBD DALY outcomes by country revealed that for some studies DALY estimates were of similar magnitude; others reported DALY estimates that were two times higher or lower.
Conclusions
Overcoming “error” variation due to the use of different methodologies and low-quality data is a critical priority for advancing burden of disease studies. This can enlarge the detection of true variation in DALY outcomes between populations or over time.
doi:10.1186/1478-7954-10-21
PMCID: PMC3554436  PMID: 23113929
Review; General burden of disease; Disability-adjusted life years; Methodology
21.  Alveolar echinococcosis-spreading disease challenging clinicians: A case report and literature review 
Human alveolar echinococcosis (AE) is a potentially deadly disease; recent studies have shown that the endemic area of Echinococcus multilocularis, its causative agent, is larger than previously known. This disease has low prevalence and remains underreported in Europe. Emerging clinical data show that diagnostic difficulties are still common. We report on a 76-year old patient suffering from AE lesions restricted to the left lobe of the liver who underwent a curative extended left hemihepatectomy. Prior to the resection a liver biopsy under the suspicion of an atypical malignancy was performed. After the intervention he developed a pseudoaneurysm of the hepatic artery that was successfully coiled. Surprisingly, during surgery, the macroscopic appearance of the tumour revealed a growth pattern that was rather typical for cystic echinococcosis (CE), i.e., a gross tumour composed of multiple large vesicles with several centimeters in diameter. In addition, there were neither extensive adhesions nor infiltrations of the neighboring pancreas and diaphragm as was expected from previous imaging results. The unexpected diagnosis of AE was confirmed by definite histopathology, specific polymerase chain reaction and serology results. This is a rare case of unusual macroscopic presentation of AE that posed immense diagnostic challenges and had an eventful course. To our knowledge this is the first case of an autochthonous infection in this particular geographic area of Germany, the federal state of Saxony. This report may provide new hints for an expanding area of risk for AE and emphasizes the risk of complications in the scope of diagnostic procedures and the limitations of modern radiological imaging.
doi:10.3748/wjg.v19.i26.4257
PMCID: PMC3710431  PMID: 23864792
Alveolar echinococcosis; Echinococcus multilocularis; Autochthonous infection; Liver resection; Hemihepatectomy
22.  Natural Infection of the Ground Squirrel (Spermophilus spp.) with Echinococcus granulosus in China 
Background
Echinococcus granulosus is usually transmitted between canid definitive hosts and ungulate intermediate hosts.
Methodology/Principal Findings
Lesions found in the livers of ground squirrels, Spermophilus dauricus/alashanicus, trapped in Ningxia Hui Autonomous Region, an area in China co-endemic for both E. granulosus and E. multilocularis, were subjected to molecular genotyping for Echinococcus spp. DNA. One of the lesions was shown to be caused by E. granulosus and subsequently by histology to contain viable protoscoleces.
Conclusions/Significance
This is the first report of a natural infection of the ground squirrel with E. granulosus. This does not provide definitive proof of a cycle involving ground squirrels and dogs or foxes, but it is clear that there is active E. granulosus transmission occurring in this area, despite a recent past decline in the dog population in southern Ningxia.
Author Summary
Echinococcus granulosus and E. multilocularis are important zoonotic pathogens that cause serious disease in humans. E. granulosus can be transmitted through sylvatic cycles, involving wild carnivores and ungulates; or via domestic cycles, usually involving dogs and farm livestock. E. multilocularis is primarily maintained in a sylvatic life-cycle between foxes and rodents. As part of extensive investigations that we undertook to update available epidemiological data and to monitor the transmission patterns of both E. granulosus and E. mulilocularis in Ningxia Hui Autonomous Region (NHAR) in northwest China, we captured small mammals on the southern slopes of Yueliang Mountain, Xiji, an area co-endemic for human alveolar echinococcosis and cystic echinococcosis. Of 500 trapped small mammals (mainly ground squirrels; Spermophilus dauricus/alashanicus), macroscopic cyst-like lesions (size range 1–10 mm) were found on the liver surface of approximately 10% animals. One of the lesions was shown by DNA analysis to be caused by E. granulosus and by histology to contain viable protoscoleces. This is the first report of a natural infection of the ground squirrel with E. granulosus. We have no definitive proof of a cycle involving ground squirrels and dogs/foxes but it is evident that there is active E. granulosus transmission occurring in this area.
doi:10.1371/journal.pntd.0000518
PMCID: PMC2737643  PMID: 19771151
23.  Serological evidence for human cystic echinococcosis in Slovenia 
Background
Cystic echinococcosis (CE) is caused by the larva of tapeworm Echinococcus granulosus. Dogs and other canids are the primary definitive hosts for this parasite. CE may develop after accidental ingestion of tapeworm eggs, excreted with the feces of these animals. In the intestine, the larvae released from the eggs are nested in the liver, lungs or other organs of livestock as intermediate hosts and humans as aberrant hosts. The aim of this study was to examine serologically whether some of the patients in Slovenia, suspected of CE by imaging findings in the liver or lungs had been infected with the larva of Echinococcus granulosus.
Methods
Between January 1, 2002 and the end of December 2006, 1323 patients suspected of having echinococcosis were screened serologically by indirect haemagglutination assay (IHA). For confirmation and differentiation of Echinococcus spp. infection, the sera of IHA-positive patients were then retested by western blot (WB).
Results
Out of 127 IHA-positive sera, 34 sera were confirmed by WB and considered specific for CE. Of 34 sera of CE-positive patients sera, 32 corresponded to the characteristic imaging findings of a liver cysts and 2 to those of lung cysts. The mean age of CE-positive patients was 58.3 years. No significant differences were found between the CE-positive patients in regard to their sex.
Conclusion
In the study, it was found out that CE was mostly spread in the same area of Slovenia as in the past, but its prevalence decreased from 4.8 per 105 inhabitants in the period 1956–1968 to 1.7 per 105 inhabitants in the period 2002–2006. In spite of the decreased prevalence of CE in the last years, it is suggested that clinicians and public health authorities, especially in the eastern parts of Slovenia where the most CE patients come from, should pay greater attention to this disease in the future.
doi:10.1186/1471-2334-8-63
PMCID: PMC2412869  PMID: 18471283
24.  Weighting Components of Composite Endpoints in Clinical Trials: An Approach Employing Disability Adjusted Life Years 
Background and Purpose
Conventional analysis of vascular prevention trials assigns equal weight to disparate vascular events of composite endpoint at variance with public’s perception of their differential impact on health outcome. This study was to apply the disability-adjusted life year (DALY) metric for differential weighting of individual vascular endpoints in trial analyses.
Methods
DALY values for the most common major endpoints in vascular prevention trials, nonfatal myocardial infarction (MI), nonfatal stroke, and vascular death, were derived using World Health Organization Global Burden of Disease Project methodology. The standardized DALYs for each event were applied to recent major primary and secondary vascular prevention trials and to hypothetical model trials.
Results
Standardized DALYs lost were 7.63 for nonfatal stroke, 5.14 for nonfatal MI, and 11.59 for vascular death. In the published trials analyses, direction of treatment effects was consistent between DALY and standard event analysis, but rank order of treatment effect changed for 10 of 18 trials. The DALY analysis also enabled to provide number-needed-to-treat values to gain one DALY: 2.1 for anticoagulation in atrial fibrillation, 2.7 for carotid endarterectomy in symptomatic stenosis, and 4.7 for clopidogrel added to aspirin in acute coronary syndrome. Hypothetical trial analyses demonstrated that the DALY metric more finely discriminates treatment effects.
Conclusions
Compared with a nonfatal MI, a nonfatal stroke causes a 1.48-fold greater loss and vascular death a 2.25-fold greater loss of DALY. DALY analysis integrates these valuations in a summary metric reflecting the net impact of therapy on patient and societal health, complementing conventional endpoint analyses.
doi:10.1161/STROKEAHA.110.600106
PMCID: PMC3109505  PMID: 21527766
DALY; vascular disease; clinical trial; treatment effect
25.  Human African Trypanosomiasis in a Rural Community, Democratic Republic of Congo 
Emerging Infectious Diseases  2007;13(2):248-254.
Human African trypanosomiasis places a substantial economic hardship on affected households.
According to the World Health Organization, human African trypanosomiasis (HAT) (sleeping sickness) caused the loss of ≈1.5 million disability-adjusted life years (DALYs) in 2002. We describe the effect of HAT during 2000–2002 in Buma, a rural community near Kinshasa in the Democratic Republic of Congo. We used retrospective questionnaire surveys to estimate HAT-related household costs and DALYs. The HAT outbreak in Buma involved 57 patients and affected 47 (21%) households. The cost to each household was equivalent to 5 months’ income for that household. The total number of HAT-related DALYs was 2,145, and interventions to control HAT averted 1,408 DALYs. The cost per DALY averted was US $17. Because HAT has a serious economic effect on households and control interventions are cost-effective, considering only global burden of disease rankings for resource allocation could lead to misguided priority setting if applied without caution in HAT-affected countries.
doi:10.3201/eid1302.060075
PMCID: PMC2725878  PMID: 17479887
Human African trypanosomiasis; DALYs; household; cost; Democratic Republic of Congo; T. b. gambiense; burden of disease; sleeping sickness; research

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