Estimating Dengue Transmission Intensity from Sero-Prevalence Surveys in Multiple Countries

BACKGROUND:Estimates of dengue transmission intensity remain ambiguous. Since the majority of infections are asymptomatic, surveillance systems substantially underestimate true rates of infection. With advances in the development of novel control measures, obtaining robust estimates of average dengue transmission intensity is key for assessing both the burden of disease from dengue and the likely impact of interventions. METHODOLOGY/PRINCIPAL FINDINGS:The force of infection (λ) and corresponding basic reproduction numbers (R0) for dengue were estimated from non-serotype (IgG) and serotype-specific (PRNT) age-stratified seroprevalence surveys identified from the literature. The majority of R0 estimates ranged from 1-4. Assuming that two heterologous infections result in complete immunity produced up to two-fold higher estimates of R0 than when tertiary and quaternary infections were included. λ estimated from IgG data were comparable to the sum of serotype-specific forces of infection derived from PRNT data, particularly when inter-serotype interactions were allowed for. CONCLUSIONS/SIGNIFICANCE:Our analysis highlights the highly heterogeneous nature of dengue transmission. How underlying assumptions about serotype interactions and immunity affect the relationship between the force of infection and R0 will have implications for control planning. While PRNT data provides the maximum information, our study shows that even the much cheaper ELISA-based assays would provide comparable baseline estimates of overall transmission intensity which will be an important consideration in resource-constrained settings

Assessment of chemical stability of monoclonal antibody and antibody drug conjugate administered by pressurized intraperitoneal aerosol chemotherapy.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new therapeutic approach for patients with peritoneal cancer. So far, most published studies investigated the administration of established cytostatic agents through PIPAC. This study aimed to evaluate the effect of PIPAC on two breakthrough anti-cancer agents, specifically anti-PD1 pembrolizumab, and anti-HER2 antibody-drug conjugate (ADC) - trastuzumab-deruxtecan. We conducted systematic analyses on samples of pembrolizumab and trastuzumab-deruxtecan at clinically relevant concentrations before and after PIPAC administration using an experimental setup of a hermetic container system, mimicking the abdominal cavity and using identical features as in clinical use. We utilized a range of chromatographic and spectroscopic techniques to explore potential alterations in the primary, secondary, and tertiary structures of the drugs, focusing on post-translational modifications resulting from the aerosolization. Our findings indicate that PIPAC did not compromise the integrity of tested biopharmaceuticals. The size variants of both drugs, assessed by size exclusion chromatography (SEC), remained unchanged. Reversed-phase liquid chromatography (RPLC) and hydrophobic interaction chromatography (HIC) revealed no significant differences in hydrophobicity variants, the average drug-to-antibody ratio (DAR), or DAR distribution before and after PIPAC treatment. Circular dichroism (CD) spectroscopy confirmed that the secondary and tertiary structures were preserved. While pembrolizumab showed no change in charge variants post-PIPAC, trastuzumab-deruxtecan exhibited a non-negligible change in the quantity of charge variants on the monoclonal antibody itself, while the payload remained unchanged. This shift could possibly be related to the metallic composition of the CapnoPen® device (made of nickel and chromium) used in PIPAC and for these experiments. Together, our results suggest that PIPAC does not alter the structure of pembrolizumab and trastuzumab-deruxtecan, paving the way for future clinical trials

Future and potential spending on health 2015-40: Development assistance for health, and government, prepaid private, and out-of-pocket health spending in 184 countries

Background: The amount of resources, particularly prepaid resources, available for health can affect access to health care and health outcomes. Although health spending tends to increase with economic development, tremendous variation exists among health financing systems. Estimates of future spending can be beneficial for policy makers and planners, and can identify financing gaps. In this study, we estimate future gross domestic product (GDP), all-sector government spending, and health spending disaggregated by source, and we compare expected future spending to potential future spending. Methods: We extracted GDP, government spending in 184 countries from 1980-2015, and health spend data from 1995-2014. We used a series of ensemble models to estimate future GDP, all-sector government spending, development assistance for health, and government, out-of-pocket, and prepaid private health spending through 2040. We used frontier analyses to identify patterns exhibited by the countries that dedicate the most funding to health, and used these frontiers to estimate potential health spending for each low-income or middle-income country. All estimates are inflation and purchasing power adjusted. Findings: We estimated that global spending on health will increase from US$9.21 trillion in 2014 to$24.24 trillion (uncertainty interval [UI] 20.47-29.72) in 2040. We expect per capita health spending to increase fastest in upper-middle-income countries, at 5.3% (UI 4.1-6.8) per year. This growth is driven by continued growth in GDP, government spending, and government health spending. Lower-middle income countries are expected to grow at 4.2% (3.8-4.9). High-income countries are expected to grow at 2.1% (UI 1.8-2.4) and low-income countries are expected to grow at 1.8% (1.0-2.8). Despite this growth, health spending per capita in low-income countries is expected to remain low, at $154 (UI 133-181) per capita in 2030 and$195 (157-258) per capita in 2040. Increases in national health spending to reach the level of the countries who spend the most on health, relative to their level of economic development, would mean $321 (157-258) per capita was available for health in 2040 in low-income countries. Interpretation: Health spending is associated with economic development but past trends and relationships suggest that spending will remain variable, and low in some low-resource settings. Policy change could lead to increased health spending, although for the poorest countries external support might remain essential

Future and potential spending on health 2015-40 : development assistance for health, and government, prepaid private, and out-of-pocket health spending in 184 countries

Background The amount of resources, particularly prepaid resources, available for health can affect access to health care and health outcomes. Although health spending tends to increase with economic development, tremendous variation exists among health financing systems. Estimates of future spending can be beneficial for policy makers and planners, and can identify financing gaps. In this study, we estimate future gross domestic product (GDP), all-sector government spending, and health spending disaggregated by source, and we compare expected future spending to potential future spending. Methods We extracted GDP, government spending in 184 countries from 1980-2015, and health spend data from 1995-2014. We used a series of ensemble models to estimate future GDP, all-sector government spending, development assistance for health, and government, out-of-pocket, and prepaid private health spending through 2040. We used frontier analyses to identify patterns exhibited by the countries that dedicate the most funding to health, and used these frontiers to estimate potential health spending for each low-income or middle-income country. All estimates are inflation and purchasing power adjusted. Findings We estimated that global spending on health will increase from US$9.21 trillion in 2014 to$24.24 trillion (uncertainty interval [UI] 20.47-29.72) in 2040. We expect per capita health spending to increase fastest in upper-middle-income countries, at 5.3% (UI 4.1-6.8) per year. This growth is driven by continued growth in GDP, government spending, and government health spending. Lower-middle income countries are expected to grow at 4.2% (3.8-4.9). High-income countries are expected to grow at 2.1% (UI 1.8-2.4) and low-income countries are expected to grow at 1.8% (1.0-2.8). Despite this growth, health spending per capita in low-income countries is expected to remain low, at $154 (UI 133-181) per capita in 2030 and$195 (157-258) per capita in 2040. Increases in national health spending to reach the level of the countries who spend the most on health, relative to their level of economic development, would mean $321 (157-258) per capita was available for health in 2040 in low-income countries. Interpretation Health spending is associated with economic development but past trends and relationships suggest that spending will remain variable, and low in some low-resource settings. Policy change could lead to increased health spending, although for the poorest countries external support might remain essential.Peer reviewe

Tool for eliminating dog-mediated human rabies through mass dog vaccination campaigns

The World Health Organization and collaborating agencies have set the goal of eliminating dog-mediated human rabies by 2030. Building on experience with rabies endemic countries, we constructed a user-friendly tool to help public health officials plan the resources needed to achieve this goal through mass vaccination of dogs

Objective assessment of electrode discrimination with the auditory change complex in adult cochlear implant users

The spatial auditory change complex (ACC) is a cortical response elicited by a change in place of stimulation. There is growing evidence that it provides a useful objective measure of electrode discrimination in cochlear implant (CI) users. To date, the spatial ACC has only been measured in relatively experienced CI users with one type of device. Early assessment of electrode discrimination could allow auditory stimulation to be optimized during a potentially sensitive period of auditory rehabilitation. In this study we used a direct stimulation paradigm to measure the spatial ACC in both pre- and post-lingually deafened adults. We show that it is feasible to measure the spatial ACC in different CI devices and as early as 1 week after CI switch-on. The spatial ACC has a strong relationship with performance on a behavioural discrimination task and in some cases provides information over and above behavioural testing. We suggest that it may be useful to measure the spatial ACC to guide auditory rehabilitation and improve hearing performance in CI users

The effect of wealth and real income on wildlife consumption among native Amazonians in Bolivia: estimates of annual trends with longitudinal household data (2002–2006)

Over the last decades, native Amazonians have put increasing pressure on animal wildlife owing to growth in demand. Across societies, household monetary income and wealth shape food consumption; hence, so it is natural to ask what effect might these variables have on the demand for wildlife consumption among native Amazonians, particularly as they gain a stronger foothold in the market economy and increasing de jure stewardship over their territories. Prior estimates of the effects of household monetary income and household wealth on wildlife consumption among native Amazonians have relied on cross-sectional data and produced unclear results. The goal of this research was to improve the precision of previous estimates by drawing on a larger sample and on longitudinal data. The analysis draws on a dataset composed of five consecutive annual surveys (2002–2006, inclusive) from 324 households in a native Amazonian society of foragers and farmers in Bolivia (Tsimane'). Multiple regression analysis is used to estimate the association between wildlife consumption and monetary income and wealth. Wildlife consumption bore a positive association with the level of household wealth and no significant association with household monetary income. Among Tsimane', the main internal threat to wildlife conservation in the short run will likely arise from increases in wealth, probably from the enhanced capacity that selected physical assets (e.g. guns) have in the capture of animal wildlif

Costs and effectiveness of alternative dog vaccination strategies to improve dog population coverage in rural and urban settings during a rabies outbreak.

Dog-rabies elimination programs have typically relied upon parenteral vaccination at central-point locations; however, dog-ownership practices, accessibility to hard-to-reach sub-populations, resource limitations, and logistics may impact a country's ability to reach the 70% coverage goal recommended by the World Organization for Animal Health (OIE) and World Health Organization (WHO). Here we report the cost-effectiveness of different dog-vaccination strategies during a dog-rabies outbreak in urban and peri-urban sections of Croix-des-Bouquets commune of the West Department, Haiti, in 2016. Three strategies, mobile static point (MSP), mobile static point with capture-vaccinate-release (MSP?+?CVR), and door-to-door vaccination with oral vaccination (DDV?+?ORV), were applied at five randomly assigned sites and assessed for free-roaming dog vaccination coverage and total population coverage. A total of 7065 dogs were vaccinated against rabies during the vaccination campaign. Overall, free-roaming dog vaccination coverage was estimated at 52% (47%-56%) for MSP, 53% (47%-60%) for DDV?+?ORV, and 65% (61%-69%) for MSP?+?CVR (differences with MSP and DDV?+?ORV significant at p?<?0.01). Total dog vaccination coverage was 33% (95% CI: 26%-43%) for MSP, 49% (95% CI: 40%-61%) for MSP?+?CVR and 78% (77%-80%) for DDV?+?ORV (differences significant at p?<?0.001). Overall, the least expensive campaign was MSP, with an estimated cost of about $2039 per day ($4078 total), and the most expensive was DDV?+?ORV with a cost of $3246 per day ($6492 total). Despite the relative high cost of an ORV bait, combining DDV and ORV was the most cost-effective strategy in our study ($1.97 per vaccinated dog), largely due to increased efficiency of the vaccinators to target less accessible dogs. Costs per vaccinated dog were$2.20 for MSP and $2.28 for MSP?+?CVR. We hope the results from this study will support the design and implementation of effective dog vaccination campaigns to achieve the goal of eliminating dog-mediated human rabies deaths by 2030

Commonality and variation in mental representations of music revealed by a cross-cultural comparison of rhythm priors in 15 countries

Music is present in every known society but varies from place to place. What, if anything, is universal to music cognition? We measured a signature of mental representations of rhythm in 39 participant groups in 15 countries, spanning urban societies and Indigenous populations. Listeners reproduced random ‘seed’ rhythms; their reproductions were fed back as the stimulus (as in the game of ‘telephone’), such that their biases (the prior) could be estimated from the distribution of reproductions. Every tested group showed a sparse prior with peaks at integer-ratio rhythms. However, the importance of different integer ratios varied across groups, often reflecting local musical practices. Our results suggest a common feature of music cognition: discrete rhythm ‘categories’ at small-integer ratios. These discrete representations plausibly stabilize musical systems in the face of cultural transmission but interact with culture-specific traditions to yield the diversity that is evident when mental representations are probed across many cultures