Summary 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.
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.
Summary 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.
Monitoring and evaluation (M&E) is a key component of large-scale neglected tropical diseases (NTD) control programs. Diagnostic tests deployed in these M&E surveys are often imperfect, and it ...remains unclear how this affects the population-based program decision-making.
We developed a 2-stage lot quality assurance sampling (LQAS) framework for decision-making that allows for both imperfect diagnostics and spatial heterogeneity of infections. We applied the framework to M&E of soil-transmitted helminth control programs as a case study. For this, we explored the impact of the diagnostic performance (sensitivity and specificity), spatial heterogeneity (intra-cluster correlation), and survey design on program decision-making around the prevalence decisions thresholds recommended by WHO (2%, 10%, 20% and 50%) and the associated total survey costs.
The survey design currently recommended by WHO (5 clusters and 50 subjects per cluster) may lead to incorrect program decisions around the 2% and 10% prevalence thresholds, even when perfect diagnostic tests are deployed. To reduce the risk of incorrect decisions around the 2% prevalence threshold, including more clusters (≥10) and deploying highly specific diagnostic methods (≥98%) are the most-cost saving strategies when spatial heterogeneity is moderate-to-high (intra-cluster correlation >0.017). The higher cost and lower throughput of improved diagnostic tests are compensated by lower required sample sizes, though only when the cost per test is <6.50 US$ and sample throughput is ≥3 per hour.
Our framework provides a means to assess and update M&E guidelines and guide product development choices for NTD. Using soil-transmitted helminths as a case study, we show that current M&E guidelines may severely fall short, particularly in low-endemic and post-control settings. Furthermore, specificity rather than sensitivity is a critical parameter to consider. When the geographical distribution of an NTD within a district is highly heterogeneous, sampling more clusters (≥10) may be required.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The COVID-19 pandemic has affected the entire world causing substantial numbers of cases and deaths in most countries. Many have implemented nationwide stringent control to avoid overburdening the ...health care system. This has paralyzed economic and social activities and may continue to do so until the large-scale availability of a vaccine. We propose an alternative exit strategy to develop herd immunity in a predictable and controllable way: a phased lift of control. This means that successive parts of the country (e.g. provinces) stop stringent control, and COVID-19-related IC admissions are distributed over the country as a whole. Importantly, vulnerable individuals need to be shielded until herd immunity has developed in their area. We explore the characteristics and duration of this strategy using a novel individual-based model for geographically stratified transmission of COVID-19 in a country. The model predicts that individuals will have to experience stringent control for about 14 months on average, but this duration may be almost halved by further developments (more IC beds, better treatments). Clearly, implementation of this strategy would have a profound impact on individuals and society, and should therefore be considered carefully by various other disciplines (e.g. health systems, ethics, economics) before actual implementation.
Many countries are currently dealing with the COVID-19 epidemic and are searching for an exit strategy such that life in society can return to normal. To support this search, computational models are ...used to predict the spread of the virus and to assess the efficacy of policy measures before actual implementation. The model output has to be interpreted carefully though, as computational models are subject to uncertainties. These can stem from, e.g., limited knowledge about input parameters values or from the intrinsic stochastic nature of some computational models. They lead to uncertainties in the model predictions, raising the question what distribution of values the model produces for key indicators of the severity of the epidemic. Here we show how to tackle this question using techniques for uncertainty quantification and sensitivity analysis. We assess the uncertainties and sensitivities of four exit strategies implemented in an agent-based transmission model with geographical stratification. The exit strategies are termed Flattening the Curve, Contact Tracing, Intermittent Lockdown and Phased Opening. We consider two key indicators of the ability of exit strategies to avoid catastrophic health care overload: the maximum number of prevalent cases in intensive care (IC), and the total number of IC patient-days in excess of IC bed capacity. Our results show that uncertainties not directly related to the exit strategies are secondary, although they should still be considered in comprehensive analysis intended to inform policy makers. The sensitivity analysis discloses the crucial role of the intervention uptake by the population and of the capability to trace infected individuals. Finally, we explore the existence of a safe operating space. For Intermittent Lockdown we find only a small region in the model parameter space where the key indicators of the model stay within safe bounds, whereas this region is larger for the other exit strategies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Soil-transmitted helminth (STH) control programs currently lack evidence-based recommendations for cost-efficient survey designs for monitoring and evaluation. Here, we present a framework to provide ...evidence-based recommendations, using a case study of therapeutic drug efficacy monitoring based on the examination of helminth eggs in stool.
We performed an in-depth analysis of the operational costs to process one stool sample for three diagnostic methods (Kato-Katz, Mini-FLOTAC and FECPAKG2). Next, we performed simulations to determine the probability of detecting a truly reduced therapeutic efficacy for different scenarios of STH species (Ascaris lumbricoides, Trichuris trichiura and hookworms), pre-treatment infection levels, survey design (screen and select (SS); screen, select and retest (SSR) and no selection (NS)) and number of subjects enrolled (100-5,000). Finally, we integrated the outcome of the cost assessment into the simulation study to estimate the total survey costs and determined the most cost-efficient survey design.
Kato-Katz allowed for both the highest sample throughput and the lowest cost per test, while FECPAKG2 required both the most laboratory time and was the most expensive. Counting of eggs accounted for 23% (FECPAKG2) or ≥80% (Kato-Katz and Mini-FLOTAC) of the total time-to-result. NS survey designs in combination with Kato-Katz were the most cost-efficient to assess therapeutic drug efficacy in all scenarios of STH species and endemicity.
We confirm that Kato-Katz is the fecal egg counting method of choice for monitoring therapeutic drug efficacy, but that the survey design currently recommended by WHO (SS) should be updated. Our generic framework, which captures laboratory time and material costs, can be used to further support cost-efficient choices for other important surveys informing STH control programs. In addition, it can be used to explore the value of alternative diagnostic techniques, like automated egg counting, which may further reduce operational costs.
ClinicalTrials.gov NCT03465488.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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. An additional challenge is to obtain all of the aforementioned values stratified by age and gender, data which are seldom available for NTDs. ...the affordable diagnostic tools typically used to measure NTDs in resource-constrained settings are inaccurate and many sequelae (i.e., morbidities) of NTDs are nonspecific, making it difficult to attribute them to a particular infection or risk factor.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To monitor and evaluate soil-transmitted helminth (STH) control programs, the World Health Organization (WHO) recommends screening stools from 250 children, deploying Kato-Katz thick smear (KK). ...However, it remains unclear whether these recommendations are sufficient to make adequate decisions about stopping preventive chemotherapy (PC) (prevalence of infection <2%) or declaring elimination of STHs as a public health problem (prevalence of moderate-to-heavy intensity (MHI) infections <2%).
We developed a simulation framework to determine the effectiveness and cost of survey designs for decision-making in STH control programs, capturing the operational resources to perform surveys, the variation in egg counts across STH species, across schools, between and within individuals, and between repeated smears. Using this framework and a lot quality assurance sampling approach, we determined the most cost-efficient survey designs (number of schools, subjects, stool samples per subject, and smears per stool sample) for decision-making.
For all species, employing duplicate KK (sampling 4 to 6 schools and 64 to 70 subjects per school) was the most cost-efficient survey design to assess whether prevalence of any infection intensity was above or under 2%. For prevalence of MHI infections, single KK was the most cost-efficient (sampling 11 to 25 schools and 52 to 84 children per school).
KK is valuable for monitoring and evaluation of STH control programs, though we recommend deploying a duplicate KK on a single stool sample to stop PC, and a single KK to declare the elimination of STHs as a public health problem.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
