Malaria: deploying a candidate vaccine (RTS,S/AS02A) for an old scourge of humankind

Malaria is an infectious disease caused by the protist Plasmodium spp. and it currently kills more than one million people annually. The burden of malaria is concentrated in sub-Saharan Africa, India, and Southeast Asia. The parasite’s resistance to commonly used anti-malarial drugs has worsened the situation in the poorest countries. The World Health Organization (WHO) estimates that more than 100 countries suffer from endemic malaria episodes. In addition to numerous control measures and treatments, several vaccines are at different research stages and trials. We have assayed RTS,S/AS02A, a pre-erythrocytic candidate vaccine that has shown promising protection levels in phase IIb trials in Mozambique. The vaccine is directed against the sporozoite form of the parasite, which is injected by the mosquito Anopheles spp. The vaccine induces a strong antibody response and stimulates Th1 cells—a subset of helper T cells that participates in cell-mediated immunity. Recent interest by international funding agencies has provided new inputs into initiatives and programs to fight malaria, which, under normal welfare and adequate social development conditions, is a curable disease. [Int Microbiol 2006; 9(2):83-93

Approaching the Target: the Path Towards an Effective Malaria Vaccine

Developing an effective malaria vaccine has been the goal of the scientific community for many years. A malaria vaccine, added to existing tools and strategies, would further prevent infection and decrease the unacceptable malaria morbidity and mortality burden. Great progress has been made over the last decade and a number of vaccine candidates are in the clinical phases of development. The RTS,S malaria vaccine candidate, based on a recombinant P. falciparum protein, is the most advanced of such candidates, currently undergoing a large phase III trial. RTS,S has consistently shown around 50% efficacy protecting against the first clinical episode of malaria, in some cases extending up to 4 years. It is hoped that RTS,S will eventually become the first licensed malaria vaccine. This first vaccine against a human parasite is a groundbreaking achievement, but improved malaria vaccines conferring higher protection will be needed if the aspiration of malaria eradication is to be achieved

Some Lessons for the Future from the Global Malaria Eradication Programme (1955–1969)

Jose Najera and colleagues identify lessons from the Global Malaria Eradication Programme (1955–1969) relevant to current elimination and eradication efforts

Phenology of myxomycetes in Turrialba, Costa Rica

Long-term monitoring and phenological patterns of microbial communities are rare in the scientific literature. Myxomycetes have life cycle characteristics that allow both to be documented. The present study summarizes the integrated floristic and bioclimatic components of a 30-month assessment of myxomycete sporocarps in a premontane tropical forest in Turrialba, Costa Rica. Based on monthly visits and a standard sampling effort of 120 minutes per visit, myxomycetes were recorded on leaves, twigs, and logs on the ground by two to three people in 20-minute periods associated with six different collecting sites within a 34-hectare successional forest patch. Biological data were analyzed using three recorded climatic variables obtained in situ during the complete period of study. Also, the Oceanic Niño Index (ONI), provided by NOAA, an estimate of El Niño-Southern Oscillation (ENSO), was evaluated in the analyses. Overall, 54 species and 2245 records of myxomycetes were recorded, with an average of 14.5 species (range between 6-24) and 78.4 records (range between 20-110) detected each month. In general, neither the number of records nor the number of species were associated with individual climate variables, but multiple regression analyses showed that a combination of the accumulated precipitation of the four days before sampling and the average relative humidity can explain most of the fruiting dynamics (R2 = 0.56). When the ONI index was included in the analyses, the explained variability increased (R2 = 0.64), and when a categorization of months based on the same index was used, analyses showed that both the number of records and species evenness were affected by ENSO. At the species level, Hemitrichia calyculata was the only species observed during every month, closely followed by Arcyria cinerea, A. denudata, and Physarum compressum, recorded on most visits. Sporadic fruiting in some species such as Tubifera microsperma, P. tenerum, P. bogoriense, P. melleum, and Metatrichia vesparia could have been associated with local climate oscillations influenced by ENSO patterns. Phenological patterns were observed at the species level, indicating that in the Neotropics, under favorable conditions, myxomycete sporocarps are practically always present, but species assemblages vary temporally. These variations are primarily driven by local climate, but regional climate dynamics also affect fruiting patterns. Presumably, the remaining ecological effect on fruiting patterns in the Neotropics can be attributed to certain finer factors such as ecosystem structure, substrate quality/ availability, and biotic interactions. As such, phenomena such as climate change can have an important effect on the production of sporocarps by tropical myxomycetes, with subsequent effects of their ecological dynamics.Universidad de Costa Rica/[570-B8-006]/UCR/Costa RicaUCR::Sedes Regionales::Sede del Atlántico::Recinto de Paraíso::Finca Experimental Interdisciplinaria de Modelos Agroecológicos (FEIMA)UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ingeniería::Instituto Investigaciones en Ingeniería (INII

Curved dilatonic brane-worlds and the cosmological constant problem

We construct a model for dilatonic brane worlds with constant curvature on the brane, i.e. a non-zero four-dimensional cosmological constant, given in function of the dilaton coupling and the cosmological constant of the bulk. We compare this family of solutions to other known dilatonic domain wall solutions and apply a self-tunning mechanism to check the stability of our solutions under quantum fluctuations living on the brane.Comment: latex, 6 pages. (v2): considerable changes in the conclusion. (v3): added new discussion on the solutions and some references; version to appear in CQ

Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017

Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the healthrelated SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030

Determinants of household demand for bed nets in a rural area of southern Mozambique

<p>Abstract</p> <p>Background</p> <p>A key to making insecticide-treated nets (ITNs) a long-term, sustainable solution to the spread of malaria is understanding what drives their purchase and use. Few studies have analysed the determinants of demand for bed nets for malaria prevention at the household level, and in particular, how demand for nets compares with demand for other mosquito prevention methods.</p> <p>Methods</p> <p>This study uses a household survey to assess the determinants of demand for bed nets in an area of endemic malaria transmission in rural, southern Mozambique. The study looks at willingness to pay (WTP) for bed nets, net ownership, usage, and past purchase behaviour, alongside expenditure and frequency of use of alternate methods for malaria prevention.</p> <p>Results</p> <p>While overall net ownership in the sample is low, the evidence fails to suggest that poorer households are less likely to own bed nets, when controlling for covariates, nor does the likelihood of receiving a free net depend on socioeconomic status (SES). Formal schooling and market knowledge seem to indicate higher average willingness to pay, while use of alternate methods for malaria prevention, and receipt of Indoor Residual Spraying (IRS) are found to decrease demand for bed nets.</p> <p>Conclusion</p> <p>For long-term sustainability of ITNs to be realized, results suggest that either full or partial subsidies may be necessary in some contexts to encourage households to obtain and use nets. Given the possible substitution effects of combined malaria control interventions, and the danger of not taking into consideration household preferences for malaria prevention, successful malaria control campaigns should invest a portion of their funds towards educating recipients of IRS and users of other preventive methods on the importance of net use even in the absence of mosquitoes.</p

Spatio-temporal analysis of mortality among children under the age of five in Manhiça (Mozambique) during the period 1997-2005

<p>Abstract</p> <p>Background</p> <p>Reducing childhood mortality is the fourth goal of the Millennium Development Goals agreed at the United Nations Millennium Summit in September 2000. However, childhood mortality in developing countries remains high. Providing an accurate picture of space and time-trend variations in child mortality in a region might generate further ideas for health planning actions to achieve such a reduction. The purpose of this study was to examine the spatio-temporal variation for child mortality rates in Manhiça, a district within the Maputo province of southern rural Mozambique during the period 1997-2005 using a proper generalized linear mixed model.</p> <p>Results</p> <p>The results showed that childhood mortality in all the area was modified from year to year describing a convex time-trend but the spatial pattern described by the neighbourhood-specific underlying mortality rates did not change during the entire period from 1997 to 2005, where neighbourhoods with highest risks are situated in the peripheral side of the district. The spatial distribution, though more blurred here, was similar to the spatial distribution of child malaria incidence in the same area. The peak in mortality rates observed in 2001 could have been caused by the precipitation system that started in early February 2000, following which heavy rains flooded parts of Mozambique's southern provinces. However, the mortality rates at the end of the period returned to initial values.</p> <p>Conclusions</p> <p>The results of this study suggest that the health intervention programmes established in Manhiça to alleviate the effects of flooding on child mortality should cover a period of around five years and that special attention might be focused on eradicating malaria transmission. These outcomes also suggest the utility of suitably modelling space-time trend variations in a region when a point effect of an environmental factor affects all the study area.</p

Varying efficacy of intermittent preventive treatment for malaria in infants in two similar trials: public health implications.

BACKGROUND\ud \ud Intermittent preventive treatment (IPTi) with sulphadoxine-pyrimethamine (SP) in infants resulted in different estimates of clinical malaria protection in two trials that used the same protocol in Ifakara, Tanzania, and Manhiça, Mozambique. Understanding the reasons for the discrepant results will help to elucidate the action mechanism of this intervention, which is essential for rational policy formulation.\ud \ud METHODS\ud \ud A comparative analysis of two IPTi trials that used the same study design, follow-up, intervention, procedures and assessment of outcomes, in Tanzania and Mozambique was undertaken. Children were randomised to receive either SP or placebo administered 3 times alongside routine vaccinations delivered through the Expanded Program on Immunisation (EPI). Characteristics of the two areas and efficacy on clinical malaria after each dose were compared.\ud \ud RESULTS\ud \ud The most relevant difference was in ITN's use ; 68% in Ifakara and zero in Manhiça. In Ifakara, IPTi was associated with a 53% (95% CI 14.0; 74.1) reduction in the risk of clinical malaria between the second and the third dose; during the same period there was no significant effect in Manhiça. Similarly, protection against malaria episodes was maintained in Ifakara during 6 months after dose 3, but no effect of IPTi was observed in Manhiça.\ud \ud CONCLUSION\ud \ud The high ITN coverage in Ifakara is the most likely explanation for the difference in IPTi efficacy on clinical malaria. Combination of IPTi and ITNs may be the most cost-effective tool for malaria control currently available, and needs to be explored in current and future studies.\ud \ud TRIAL REGISTRATION\ud \ud Manhiça study registration number: NCT00209795Ifakara study registration number: NCT88523834