A sticky situation: the unexpected stability of malaria elimination

Malaria eradication involves eliminating malaria from every country where transmission occurs. Current theory suggests that the post-elimination challenges of remaining malaria-free by stopping transmission from imported malaria will have onerous operational and financial requirements. Although resurgent malaria has occurred in a majority of countries that tried but failed to eliminate malaria, a review of resurgence in countries that successfully eliminated finds only four such failures out of 50 successful programmes. Data documenting malaria importation and onwards transmission in these countries suggests malaria transmission potential has declined by more than 50-fold (i.e. more than 98%) since before elimination. These outcomes suggest that elimination is a surprisingly stable state. Elimination''s ‘stickiness’ must be explained either by eliminating countries starting off qualitatively different from non-eliminating countries or becoming different once elimination was achieved. Countries that successfully eliminated were wealthier and had lower baseline endemicity than those that were unsuccessful, but our analysis shows that those same variables were at best incomplete predictors of the patterns of resurgence. Stability is reinforced by the loss of immunity to disease and by the health system''s increasing capacity to control malaria transmission after elimination through routine treatment of cases with antimalarial drugs supplemented by malaria outbreak control. Human travel patterns reinforce these patterns; as malaria recedes, fewer people carry malaria from remote endemic areas to remote areas where transmission potential remains high. Establishment of an international resource with backup capacity to control large outbreaks can make elimination stickier, increase the incentives for countries to eliminate, and ensure steady progress towards global eradication. Although available evidence supports malaria elimination''s stickiness at moderate-to-low transmission in areas with well-developed health systems, it is not yet clear if such patterns will hold in all areas. The sticky endpoint changes the projected costs of maintaining elimination and makes it substantially more attractive for countries acting alone, and it makes spatially progressive elimination a sensible strategy for a malaria eradication endgame.     

Entrepreneurial Regions: Do Macro-Psychological Cultural Characteristics of Regions Help Solve the “Knowledge Paradox” of Economics?

In recent years, modern economies have shifted away from being based on physical capital and towards being based on new knowledge (e.g., new ideas and inventions). Consequently, contemporary economic theorizing and key public policies have been based on the assumption that resources for generating knowledge (e.g., education, diversity of industries) are essential for regional economic vitality. However, policy makers and scholars have discovered that, contrary to expectations, the mere presence of, and investments in, new knowledge does not guarantee a high level of regional economic performance (e.g., high entrepreneurship rates). To date, this “knowledge paradox” has resisted resolution. We take an interdisciplinary perspective to offer a new explanation, hypothesizing that “hidden” regional culture differences serve as a crucial factor that is missing from conventional economic analyses and public policy strategies. Focusing on entrepreneurial activity, we hypothesize that the statistical relation between knowledge resources and entrepreneurial vitality (i.e., high entrepreneurship rates) in a region will depend on “hidden” regional differences in entrepreneurial culture. To capture such “hidden” regional differences, we derive measures of entrepreneurship-prone culture from two large personality datasets from the United States (N = 935,858) and Great Britain (N = 417,217). In both countries, the findings were consistent with the knowledge-culture-interaction hypothesis. A series of nine additional robustness checks underscored the robustness of these results. Naturally, these purely correlational findings cannot provide direct evidence for causal processes, but the results nonetheless yield a remarkably consistent and robust picture in the two countries. In doing so, the findings raise the idea of regional culture serving as a new causal candidate, potentially driving the knowledge paradox; such an explanation would be consistent with research on the psychological characteristics of entrepreneurs.     

Climate change and heat-related mortality in six cities Part 2: climate model evaluation and projected impacts from changes in the mean and variability of temperature with climate change

Previous assessments of the impacts of climate change on heat-related mortality use the “delta method” to create temperature projection time series that are applied to temperature–mortality models to estimate future mortality impacts. The delta method means that climate model bias in the modelled present does not influence the temperature projection time series and impacts. However, the delta method assumes that climate change will result only in a change in the mean temperature but there is evidence that there will also be changes in the variability of temperature with climate change. The aim of this paper is to demonstrate the importance of considering changes in temperature variability with climate change in impacts assessments of future heat-related mortality. We investigate future heat-related mortality impacts in six cities (Boston, Budapest, Dallas, Lisbon, London and Sydney) by applying temperature projections from the UK Meteorological Office HadCM3 climate model to the temperature–mortality models constructed and validated in Part 1. We investigate the impacts for four cases based on various combinations of mean and variability changes in temperature with climate change. The results demonstrate that higher mortality is attributed to increases in the mean and variability of temperature with climate change rather than with the change in mean temperature alone. This has implications for interpreting existing impacts estimates that have used the delta method. We present a novel method for the creation of temperature projection time series that includes changes in the mean and variability of temperature with climate change and is not influenced by climate model bias in the modelled present. The method should be useful for future impacts assessments. Few studies consider the implications that the limitations of the climate model may have on the heat-related mortality impacts. Here, we demonstrate the importance of considering this by conducting an evaluation of the daily and extreme temperatures from HadCM3, which demonstrates that the estimates of future heat-related mortality for Dallas and Lisbon may be overestimated due to positive climate model bias. Likewise, estimates for Boston and London may be underestimated due to negative climate model bias. Finally, we briefly consider uncertainties in the impacts associated with greenhouse gas emissions and acclimatisation. The uncertainties in the mortality impacts due to different emissions scenarios of greenhouse gases in the future varied considerably by location. Allowing for acclimatisation to an extra 2°C in mean temperatures reduced future heat-related mortality by approximately half that of no acclimatisation in each city.     

Personality Consistency in Dogs: A Meta-Analysis

Personality, or consistent individual differences in behavior, is well established in studies of dogs. Such consistency implies predictability of behavior, but some recent research suggests that predictability cannot be assumed. In addition, anecdotally, many dog experts believe that ‘puppy tests’ measuring behavior during the first year of a dog''s life are not accurate indicators of subsequent adult behavior. Personality consistency in dogs is an important aspect of human-dog relationships (e.g., when selecting dogs suitable for substance-detection work or placement in a family). Here we perform the first comprehensive meta-analysis of studies reporting estimates of temporal consistency of dog personality. A thorough literature search identified 31 studies suitable for inclusion in our meta-analysis. Overall, we found evidence to suggest substantial consistency (r = 0.43). Furthermore, personality consistency was higher in older dogs, when behavioral assessment intervals were shorter, and when the measurement tool was exactly the same in both assessments. In puppies, aggression and submissiveness were the most consistent dimensions, while responsiveness to training, fearfulness, and sociability were the least consistent dimensions. In adult dogs, there were no dimension-based differences in consistency. There was no difference in personality consistency in dogs tested first as puppies and later as adults (e.g., ‘puppy tests’) versus dogs tested first as puppies and later again as puppies. Finally, there were no differences in consistency between working versus non-working dogs, between behavioral codings versus behavioral ratings, and between aggregate versus single measures. Implications for theory, practice, and future research are discussed.     

High Resistance of Plasmodium falciparum to Sulphadoxine/Pyrimethamine in Northern Tanzania and the Emergence of dhps Resistance Mutation at Codon 581

Background

Sulphadoxine-pyrimethamine (SP) a widely used treatment for uncomplicated malaria and recommended for intermittent preventive treatment of malaria in pregnancy, is being investigated for intermittent preventive treatment of malaria in infants (IPTi). High levels of drug resistance to SP have been reported from north-eastern Tanzania associated with mutations in parasite genes. This study compared the in vivo efficacy of SP in symptomatic 6–59 month children with uncomplicated malaria and in asymptomatic 2–10 month old infants.

Methodology and Principal Findings

An open label single arm (SP) standard 28 day in vivo WHO antimalarial efficacy protocol was used in 6 to 59 months old symptomatic children and a modified protocol used in 2 to 10 months old asymptomatic infants. Enrolment was stopped early (87 in the symptomatic and 25 in the asymptomatic studies) due to the high failure rate. Molecular markers were examined for recrudescence, re-infection and markers of drug resistance and a review of literature of studies looking for the 581G dhps mutation was carried out. In symptomatic children PCR-corrected early treatment failure was 38.8% (95% CI 26.8–50.8) and total failures by day 28 were 82.2% (95% CI 72.5–92.0). There was no significant difference in treatment failures between asymptomatic and symptomatic children. 96% of samples carried parasites with mutations at codons 51, 59 and 108 in the dhfr gene and 63% carried a double mutation at codons 437 and 540. 55% carried a third mutation with the addition of a mutation at codon 581 in the dhps gene. This triple: triple haplotype maybe associated with earlier treatment failure.

Conclusion

In northern Tanzania SP is a failed drug for treatment and its utility for prophylaxis is doubtful. The study found a new combination of parasite mutations that maybe associated with increased and earlier failure.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00361114","term_id":"NCT00361114"}}NCT00361114     

Climate change and heat-related mortality in six cities Part 1: model construction and validation

Heat waves are expected to increase in frequency and magnitude with climate change. The first part of a study to produce projections of the effect of future climate change on heat-related mortality is presented. Separate city-specific empirical statistical models that quantify significant relationships between summer daily maximum temperature (T _max) and daily heat-related deaths are constructed from historical data for six cities: Boston, Budapest, Dallas, Lisbon, London, and Sydney. ‘Threshold temperatures’ above which heat-related deaths begin to occur are identified. The results demonstrate significantly lower thresholds in ‘cooler’ cities exhibiting lower mean summer temperatures than in ‘warmer’ cities exhibiting higher mean summer temperatures. Analysis of individual ‘heat waves’ illustrates that a greater proportion of mortality is due to mortality displacement in cities with less sensitive temperature–mortality relationships than in those with more sensitive relationships, and that mortality displacement is no longer a feature more than 12 days after the end of the heat wave. Validation techniques through residual and correlation analyses of modelled and observed values and comparisons with other studies indicate that the observed temperature–mortality relationships are represented well by each of the models. The models can therefore be used with confidence to examine future heat-related deaths under various climate change scenarios for the respective cities (presented in Part 2).