Luc E. Coffeng

The Global Burden of Disease Study 2010: Interpretation and Implications for the Neglected Tropical Diseases

The publication of the Global Burden of Disease Study 2010 (GBD 2010) and the accompanying collection of Lancet articles in December 2012 provided the most comprehensive attempt to quantify the burden of almost 300 diseases, injuries, and risk factors, including neglected tropical diseases (NTDs) [1]–[3]. The disability-adjusted life year (DALY), the metric used in the GBD 2010, is a tool which may be used to assess and compare the relative impact of a number of diseases locally and globally [4]–[6]. Table 1 lists the major NTDs as defined by the World Health Organization (WHO) [7] and their estimated DALYs [1]. With a few exceptions, most of the NTDs currently listed by the WHO [7] or those on the expanded list from PLOS Neglected Tropical Diseases [8] are disablers rather than killers, so the DALY estimates represent one of the few metrics available that could fully embrace the chronic effects of these infections. Table 1 Estimated DALYs (in millions) of the NTDs from the Global Burden of Disease Study 2010. Disease DALYs from GBD 2010 (numbers in parentheses indicate 95% confidence intervals) [1] NTDs 26.06 (20.30–35.12) Intestinal nematode infections 5.19 (2.98–8.81) Hookworm disease 3.23 (1.70–5.73) Ascariasis 1.32 (0.71–2.35) Trichuriasis 0.64 (0.35–1.06) Leishmaniasis 3.32 (2.18–4.90) Schistosomiasis 3.31 (1.70–6.26) Lymphatic filariasis 2.78 (1.8–4.00) Food-borne trematodiases 1.88 (0.70–4.84) Rabies 1.46 ((0.85–2.66) Dengue 0.83 (0.34–1.41) African trypanosomiasis 0.56 (0.08–1.77) Chagas disease 0.55 (0.27–1.05) Cysticercosis 0.50 (0.38–0.66) Onchocerciasis 0.49 (0.36–0.66) Trachoma 0.33 (0.24–0.44) Echinococcosis 0.14 (0.07–0.29) Yellow fever <0.001 Other NTDs * 4.72 (3.53–6.35) Open in a separate window * Relapsing fevers, typhus fever, spotted fever, Q fever, other rickettsioses, other mosquito-borne viral fevers, unspecified arthropod-borne viral fever, arenaviral haemorrhagic fever, toxoplasmosis, unspecified protozoal disease, taeniasis, diphyllobothriasis and sparganosis, other cestode infections, dracunculiasis, trichinellosis, strongyloidiasis, enterobiasis, and other helminthiases. Even DALYs, however, do not tell the complete story of the harmful effects from NTDs. Some of the specific and potential shortcomings of GBD 2010 have been highlighted elsewhere [9]. Furthermore, DALYs measure only direct health loss and, for example, do not consider the economic impact of the NTDs that results from detrimental effects on school attendance and child development, agriculture (especially from zoonotic NTDs), and overall economic productivity [10], [11]. Nor do DALYs account for direct costs of treatment, surveillance, and prevention measures. Yet, economic impact has emerged as an essential feature of the NTDs, which may trap people in a cycle of poverty and disease [10]–[12]. Additional aspects not considered by the DALY metrics are the important elements of social stigma for many of the NTDs and the spillover effects to family and community members [13], [14], loss of tourism [15], and health system overload (e.g., during dengue outbreaks). Ultimately NTD control and elimination efforts could produce social and economic benefits not necessarily reflected in the DALY metrics, especially among the most affected poor communities [11].

The global burden of dengue: an analysis from the Global Burden of Disease Study 2013

BACKGROUND Dengue is the most common arbovirus infection globally, but its burden is poorly quantified. We estimated dengue mortality, incidence, and burden for the Global Burden of Disease Study 2013. METHODS We modelled mortality from vital registration, verbal autopsy, and surveillance data using the Cause of Death Ensemble Modelling tool. We modelled incidence from officially reported cases, and adjusted our raw estimates for under-reporting based on published estimates of expansion factors. In total, we had 1780 country-years of mortality data from 130 countries, 1636 country-years of dengue case reports from 76 countries, and expansion factor estimates for 14 countries. FINDINGS We estimated an average of 9221 dengue deaths per year between 1990 and 2013, increasing from a low of 8277 (95% uncertainty estimate 5353-10 649) in 1992, to a peak of 11 302 (6790-13 722) in 2010. This yielded a total of 576 900 (330 000-701 200) years of life lost to premature mortality attributable to dengue in 2013. The incidence of dengue increased greatly between 1990 and 2013, with the number of cases more than doubling every decade, from 8·3 million (3·3 million-17·2 million) apparent cases in 1990, to 58·4 million (23·6 million-121·9 million) apparent cases in 2013. When accounting for disability from moderate and severe acute dengue, and post-dengue chronic fatigue, 566 000 (186 000-1 415 000) years lived with disability were attributable to dengue in 2013. Considering fatal and non-fatal outcomes together, dengue was responsible for 1·14 million (0·73 million-1·98 million) disability-adjusted life-years in 2013. INTERPRETATION Although lower than other estimates, our results offer more evidence that the true symptomatic incidence of dengue probably falls within the commonly cited range of 50 million to 100 million cases per year. Our mortality estimates are lower than those presented elsewhere and should be considered in light of the totality of evidence suggesting that dengue mortality might, in fact, be substantially higher. FUNDING Bill & Melinda Gates Foundation.

African Programme for Onchocerciasis Control 1995–2015: Model-Estimated Health Impact and Cost

Background Onchocerciasis causes a considerable disease burden in Africa, mainly through skin and eye disease. Since 1995, the African Programme for Onchocerciasis Control (APOC) has coordinated annual mass treatment with ivermectin in 16 countries. In this study, we estimate the health impact of APOC and the associated costs from a program perspective up to 2010 and provide expected trends up to 2015. Methods and Findings With data on pre-control prevalence of infection and population coverage of mass treatment, we simulated trends in infection, blindness, visual impairment, and severe itch using the micro-simulation model ONCHOSIM, and estimated disability-adjusted life years (DALYs) lost due to onchocerciasis. We assessed financial costs for APOC, beneficiary governments, and non-governmental development organizations, excluding cost of donated drugs. We estimated that between 1995 and 2010, mass treatment with ivermectin averted 8.2 million DALYs due to onchocerciasis in APOC areas, at a nominal cost of about US

Global burden of cutaneous leishmaniasis: a cross-sectional analysis from the Global Burden of Disease Study 2013.

257 million. We expect that APOC will avert another 9.2 million DALYs between 2011 and 2015, at a nominal cost of US

African Programme for Onchocerciasis Control 1995-2015: updated health impact estimates based on new disability weights

221 million. Conclusions Our simulations suggest that APOC has had a remarkable impact on population health in Africa between 1995 and 2010. This health impact is predicted to double during the subsequent five years of the program, through to 2015. APOC is a highly cost-effective public health program. Given the anticipated elimination of onchocerciasis from some APOC areas, we expect even more health gains and a more favorable cost-effectiveness of mass treatment with ivermectin in the near future.

Quantitative analyses and modelling to support achievement of the 2020 goals for nine neglected tropical diseases

BACKGROUND High-quality epidemiological studies evaluating the burden of cutaneous leishmaniasis worldwide are lacking. We compared the burden of cutaneous leishmaniasis in each country to the overall global burden and assessed the equality of cutaneous leishmaniasis burden across different countries and regions. METHODS Data were extracted from scientific literature, hospital sources, country reports, and WHO sources on the prevalence of sequalae of both acute and chronic cutaneous leishmaniasis. Prevalence data were combined with a disability weight to yield years lived with disability. Disability-adjusted life-years (DALYs) are a sum of the years lived with disability and years of life lost (or mortality, assumed to be zero). We compared DALYs due to cutaneous leishmaniasis for 152 countries using standard Z score analysis with Bonferroni correction (p<0·003) and generation of Lorenz curves with a Gini coefficient. FINDINGS In 2013, the global mean age-standardised DALYs for cutaneous leishmaniasis was 0·58 per 100 000 people. Nine countries had significantly greater DALYs from cutaneous leishmaniasis than the mean: Afghanistan (87·0), Sudan (20·2), Syria (9·2), Yemen (6·2), Iraq (6·0), Burkina Faso (4·8), Bolivia (4·6), Haiti (4·1), and Peru (4·0). The Gini coefficient was 0·89. Andean Latin America, North Africa and Middle East, western sub-Saharan Africa, and south Asia had the highest DALYs from cutaneous leishmaniasis. Among males, Palestine had the highest incidence rates (616·2 cases per 100 000 people) followed by Afghanistan (566·4), Syria (357·1), and Nicaragua (354·8). Among females, Afghanistan had the highest incidence rates (623·9) followed by Syria (406·3), Palestine (222·1), and Nicaragua (180·8). Similar proportions of males and females had cutaneous leishmaniasis in most countries with a high incidence. INTERPRETATION The burden from cutaneous leishmaniasis mainly falls on countries in Africa and the Middle East. Global and national data on the burden of cutaneous leishmaniasis disease are pivotal to promote field studies and initiate behavioural change. FUNDING Bill & Melinda Gates Foundation.

Global skin disease morbidity and mortality an update from the global burden of disease study 2013

Since 1995, the African Programme for Onchocerciasis Control (APOC) has coordinated mass treatment with ivermectin in sixteen sub-Saharan countries with the aim to control morbidity due to infection with Onchocerca volvulus, a filarial nematode. The authors predicted trends in prevalence of infection, visual impairment,blindness, and troublesome itch due to onchocerciasis in APOC countries for the period 1995–2015, based on extensive data on pre-control infection levels, population coverage of ivermectin mass treatment, and the association between infection and morbidity . They also estimated the associated health impact, expressed in disability-adjusted life years (DALYs). However, the estimated health impact was based on disability weights from the 2004 update of the Global Burden of Disease (GBD) study, which have been criticized for being based solely on the opinions of health professionals . The published GBD 2010 study addressed the criticism by providing updated disability weights based on household surveys in Bangladesh, Indonesia, Peru, and Tanzania, an open internet survey, and a telephone survey in the United States . As a result of this populationbased approach, the disability weights for visual impairment, blindness, and troublesome itch have changed considerably and should better reflect our ideas and beliefs as a society of what constitutes health.

Elimination of African Onchocerciasis: Modeling the Impact of Increasing the Frequency of Ivermectin Mass Treatment

Quantitative analysis and mathematical models are useful tools in informing strategies to control or eliminate disease. Currently, there is an urgent need to develop these tools to inform policy to achieve the 2020 goals for neglected tropical diseases (NTDs). In this paper we give an overview of a collection of novel model-based analyses which aim to address key questions on the dynamics of transmission and control of nine NTDs: Chagas disease, visceral leishmaniasis, human African trypanosomiasis, leprosy, soil-transmitted helminths, schistosomiasis, lymphatic filariasis, onchocerciasis and trachoma. Several common themes resonate throughout these analyses, including: the importance of epidemiological setting on the success of interventions; targeting groups who are at highest risk of infection or re-infection; and reaching populations who are not accessing interventions and may act as a reservoir for infection,. The results also highlight the challenge of maintaining elimination ‘as a public health problem’ when true elimination is not reached. The models elucidate the factors that may be contributing most to persistence of disease and discuss the requirements for eventually achieving true elimination, if that is possible. Overall this collection presents new analyses to inform current control initiatives. These papers form a base from which further development of the models and more rigorous validation against a variety of datasets can help to give more detailed advice. At the moment, the models’ predictions are being considered as the world prepares for a final push towards control or elimination of neglected tropical diseases by 2020.

The global burden of disease study 2013: What does it mean for the NTDs?

Importance Disability secondary to skin conditions is substantial worldwide. The Global Burden of Disease Study 2013 includes estimates of global morbidity and mortality due to skin diseases. Objective To measure the burden of skin diseases worldwide. Data Sources For nonfatal estimates, data were found by literature search using PubMed and Google Scholar in English and Spanish for years 1980 through 2013 and by accessing administrative data on hospital inpatient and outpatient episodes. Data for fatal estimates were based on vital registration and verbal autopsy data. Study Selection Skin disease data were extracted from more than 4000 sources including systematic reviews, surveys, population-based disease registries, hospital inpatient data, outpatient data, cohort studies, and autopsy data. Data metrics included incidence, prevalence, remission, duration, severity, deaths, and mortality risk. Data Extraction and Synthesis Data were extracted by age, time period, case definitions, and other study characteristics. Data points were modeled with Bayesian meta-regression to generate estimates of morbidity and mortality metrics for skin diseases. All estimates were made with 95% uncertainty intervals. Main Outcomes and Measures Disability-adjusted life years (DALYs), years lived with disability, and years of life lost from 15 skin conditions in 188 countries. Results Skin conditions contributed 1.79% to the global burden of disease measured in DALYs from 306 diseases and injuries in 2013. Individual skin diseases varied in size from 0.38% of total burden for dermatitis (atopic, contact, and seborrheic dermatitis), 0.29% for acne vulgaris, 0.19% for psoriasis, 0.19% for urticaria, 0.16% for viral skin diseases, 0.15% for fungal skin diseases, 0.07% for scabies, 0.06% for malignant skin melanoma, 0.05% for pyoderma, 0.04% for cellulitis, 0.03% for keratinocyte carcinoma, 0.03% for decubitus ulcer, and 0.01% for alopecia areata. All other skin and subcutaneous diseases composed 0.12% of total DALYs. Conclusions and Relevance Skin and subcutaneous diseases were the 18th leading cause of global DALYs in Global Burden of Disease 2013. Excluding mortality, skin diseases were the fourth leading cause of disability worldwide.

The global burden of psoriatic skin disease

The African Programme for Onchocerciasis Control (APOC) is currently shifting its focus from morbidity control to elimination of infection. To enhance the likelihood of elimination and speed up its achievement, programs may consider to increase the frequency of ivermectin mass treatment from annual to 6-monthly or even higher. In a computer simulation study, we examined the potential impact of increasing the mass treatment frequency for different settings. With the ONCHOSIM model, we simulated 92,610 scenarios pertaining to different assumptions about transmission conditions, history of mass treatment, the future mass treatment strategy, and ivermectin efficacy. Simulation results were used to determine the minimum remaining program duration and number of treatment rounds required to achieve 99% probability of elimination. Doubling the frequency of treatment from yearly to 6-monthly or 3-monthly was predicted to reduce remaining program duration by about 40% or 60%, respectively. These reductions come at a cost of additional treatment rounds, especially in case of 3-monthly mass treatment. Also, aforementioned reductions are highly dependent on maintained coverage, and could be completely nullified if coverage of mass treatment were to fall in the future. In low coverage settings, increasing treatment coverage is almost just as effective as increasing treatment frequency. We conclude that 6-monthly mass treatment may only be worth the effort in situations where annual treatment is expected to take a long time to achieve elimination in spite of good treatment coverage, e.g. because of unfavorable transmission conditions or because mass treatment started recently.