Seasonality of Plasmodium falciparum transmission: a systematic review

This article is fully open access and the published version is available free of charge from the jounal website.http://www.malariajournal.com/content/14/1/343Background Although Plasmodium falciparum transmission frequently exhibits seasonal patterns, the drivers of malaria seasonality are often unclear. Given the massive variation in the landscape upon which transmission acts, intra-annual fluctuations are likely influenced by different factors in different settings. Further, the presence of potentially substantial inter-annual variation can mask seasonal patterns; it may be that a location has “strongly seasonal” transmission and yet no single season ever matches the mean, or synoptic, curve. Accurate accounting of seasonality can inform efficient malaria control and treatment strategies. In spite of the demonstrable importance of accurately capturing the seasonality of malaria, data required to describe these patterns is not universally accessible and as such localized and regional efforts at quantifying malaria seasonality are disjointed and not easily generalized. Methods The purpose of this review was to audit the literature on seasonality of P. falciparum and quantitatively summarize the collective findings. Six search terms were selected to systematically compile a list of papers relevant to the seasonality of P. falciparum transmission, and a questionnaire was developed to catalogue the manuscripts. Results and discussion 152 manuscripts were identified as relating to the seasonality of malaria transmission, deaths due to malaria or the population dynamics of mosquito vectors of malaria. Among these, there were 126 statistical analyses and 31 mechanistic analyses (some manuscripts did both). Discussion Identified relationships between temporal patterns in malaria and climatological drivers of malaria varied greatly across the globe, with different drivers appearing important in different locations. Although commonly studied drivers of malaria such as temperature and rainfall were often found to significantly influence transmission, the lags between a weather event and a resulting change in malaria transmission also varied greatly by location. Conclusions The contradicting results of studies using similar data and modelling approaches from similar locations as well as the confounding nature of climatological covariates underlines the importance of a multi-faceted modelling approach that attempts to capture seasonal patterns at both small and large spatial scales. Keywords: Plasmodium falciparum ; Seasonality; Climatic driversAcknowledgements This work was supported by the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directory, Department of Homeland Security, and Fogarty International Center, National Institutes of Health. DLS is funded by a grant from the Bill & Melinda Gates Foundation (OPP1110495), which also supports RCR. PMA is grateful to the University of Utrecht for supporting him with The Belle van Zuylen Chair. PWG is a Career Development Fellow (K00669X) jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and receives support from the Bill and Melinda Gates Foundation (OPP1068048, OPP1106023)

Indoor Residual Spraying in Combination with Insecticide-Treated Nets Compared to Insecticide-Treated Nets Alone for Protection against Malaria: A Cluster Randomised Trial in Tanzania.

Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) of houses provide effective malaria transmission control. There is conflicting evidence about whether it is more beneficial to provide both interventions in combination. A cluster randomised controlled trial was conducted to investigate whether the combination provides added protection compared to ITNs alone. In northwest Tanzania, 50 clusters (village areas) were randomly allocated to ITNs only or ITNs and IRS. Dwellings in the ITN+IRS arm were sprayed with two rounds of bendiocarb in 2012. Plasmodium falciparum prevalence rate (PfPR) in children 0.5-14 y old (primary outcome) and anaemia in children <5 y old (secondary outcome) were compared between study arms using three cross-sectional household surveys in 2012. Entomological inoculation rate (secondary outcome) was compared between study arms. IRS coverage was approximately 90%. ITN use ranged from 36% to 50%. In intention-to-treat analysis, mean PfPR was 13% in the ITN+IRS arm and 26% in the ITN only arm, odds ratio = 0.43 (95% CI 0.19-0.97, n = 13,146). The strongest effect was observed in the peak transmission season, 6 mo after the first IRS. Subgroup analysis showed that ITN users were additionally protected if their houses were sprayed. Mean monthly entomological inoculation rate was non-significantly lower in the ITN+IRS arm than in the ITN only arm, rate ratio = 0.17 (95% CI 0.03-1.08). This is the first randomised trial to our knowledge that reports significant added protection from combining IRS and ITNs compared to ITNs alone. The effect is likely to be attributable to IRS providing added protection to ITN users as well as compensating for inadequate ITN use. Policy makers should consider deploying IRS in combination with ITNs to control transmission if local ITN strategies on their own are insufficiently effective. Given the uncertain generalisability of these findings, it would be prudent for malaria control programmes to evaluate the cost-effectiveness of deploying the combination.\ud \u

Lessons from the removal of lead from gasoline for controlling other environmental pollutants: A case study from New Zealand

<p>Abstract</p> <p>Background</p> <p>It took over two decades to achieve the removal of leaded gasoline in this country. This was despite international evidence and original research conducted in New Zealand on the harm to child cognitive function and behaviour from lead exposure.</p> <p>Objective</p> <p>To identify lessons from the New Zealand experience of removing leaded gasoline that are potentially relevant to the control of other environmental pollutants.</p> <p>Discussion</p> <p>From the available documentation, we suggest a number of reasons for the slow policy response to the leaded gasoline hazard. These include: (1) industry power in the form of successful lobbying by the lead additive supplier, Associated Octel; (2) the absence of the precautionary principle as part of risk management policy; and (3) weak policymaking machinery that included: (a) the poor use of health research evidence (from both NZ and internationally), as well as limited use of expertise in academic and non-governmental organisations; (b) lack of personnel competent in addressing technically complex issues; and (c) diffusion of responsibility among government agencies.</p> <p>Conclusion</p> <p>There is a need for a stronger precautionary approach by policymakers when considering environmental pollutants. Politicians, officials and health workers need to strengthen policymaking processes and effectively counter the industry tactics used to delay regulatory responses.</p

The Chop Gene Contains an Element for the Positive Regulation of the Mitochondrial Unfolded Protein Response

We have previously reported on the discovery of a mitochondrial specific unfolded protein response (mtUPR) in mammalian cells, in which the accumulation of unfolded protein within the mitochondrial matrix results in the transcriptional activation of nuclear genes encoding mitochondrial stress proteins such as chaperonin 60, chaperonin 10, mtDnaJ, and ClpP, but not those encoding stress proteins of the endoplasmic reticulum (ER) or the cytosol. Analysis of the chaperonin 60/10 bidirectional promoter showed that the CHOP element was required for the mtUPR and that the transcription of the chop gene is activated by mtUPR. In order to investigate the role of CHOP in the mtUPR, we carried out a deletion analysis of the chop promoter. This revealed that the transcriptional activation of the chop gene by mtUPR is through an AP-1 (activator protein-1) element. This site lies alongside an ERSE element through which chop transcription is activated in response to the ER stress response (erUPR). Thus CHOP can be induced separately in response to 2 different stress response pathways. We also discuss the potential signal pathway between mitochondria and the nucleus for the mtUPR

Distance decay in delivery care utilisation associated with neonatal mortality. A case referent study in northern Vietnam

BACKGROUND: Efforts to reduce neonatal mortality are essential if the Millennium Development Goal (MDG) 4 is to be met. The impact of spatial dimensions of neonatal survival has not been thoroughly investigated even though access to good quality delivery care is considered to be one of the main priorities when trying to reduce neonatal mortality. This study examined the association between distance from the mother's home to the closest health facility and neonatal mortality, and investigated the influence of distance on patterns of perinatal health care utilisation. METHODS: A surveillance system of live births and neonatal deaths was set up in eight districts of Quang Ninh province, Vietnam, from July 2008 to December 2009. Case referent design including all neonatal deaths and randomly selected newborn referents from the same population. Interviews were performed with mothers of all subjects and GIS coordinates for mothers' homes and all health facilities in the study area were obtained. Straight-line distances were calculated using ArcGIS software. RESULTS: A total of 197 neonatal deaths and 11 708 births were registered and 686 referents selected. Health care utilisation prior to and at delivery varied with distance to the health facility. Mothers living farthest away (4th and 5th quintile, ≥1257 meters) from a health facility had an increased risk of neonatal mortality (OR 1.96, 95% CI 1.40 - 2.75, adjusted for maternal age at delivery and marital status). When stratified for socio-economic factors there was an increased risk for neonatal mortality for mothers with low education and from poor households who lived farther away from a health facility. Mothers who delivered at home had more than twice as long to a health facility compared to mothers who delivered at a health care facility. There was no difference in age at death when comparing neonates born at home or health facility deliveries (p = 0.56). CONCLUSION: Distance to the closest health facility was negatively associated with neonatal mortality risk. Health care utilisation in the prenatal period could partly explain this risk elevation since there was a distance decay in health system usage prior to and at delivery. The geographical dimension must be taken into consideration when planning interventions for improved neonatal survival, especially when targeting socio-economically disadvantaged groups

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

The global distribution of the Duffy blood group

Blood group variants are characteristic of population groups, and can show conspicuous geographic patterns. Interest in the global prevalence of the Duffy blood group variants is multidisciplinary, but of particular importance to malariologists due to the resistance generally conferred by the Duffy-negative phenotype against Plasmodium vivax infection. Here we collate an extensive geo-database of surveys, forming the evidence-base for a multi-locus Bayesian geostatistical model to generate global frequency maps of the common Duffy alleles to refine the global cartography of the common Duffy variants. We show that the most prevalent allele globally was FY*A, while across sub-Saharan Africa the predominant allele was the silent FY*BES variant, commonly reaching fixation across stretches of the continent. The maps presented not only represent the first spatially and genetically comprehensive description of variation at this locus, but also constitute an advance towards understanding the transmission patterns of the neglected P. vivax malaria parasite

Expression of the 60 kDa and 71 kDa heat shock proteins and presence of antibodies against the 71 kDa heat shock protein in pediatric patients with immune thrombocytopenic purpura

BACKGROUND: Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by platelet destruction resulting from autoantibodies against platelet proteins, particularly platelet glycoprotein IIb/IIIa. Heat shock proteins (Hsp) have been shown to be major antigenic determinants in some autoimmune diseases. Antibodies to Hsps have also been reported to be associated with a number of pathological states. METHODS: Using western blot, we measured the levels of the 60 kDa heat shock protein (Hsp60) and of the inducible 71 kDa member of the Hsp70 family (Hsp71) in lymphocytes and the presence of antibodies against these hsps in plasma of 29 pediatric patients with ITP before the treatment and in 6 other patients before and after treatment. RESULTS: Interestingly only one out of 29 patients showed detectable Hsp60 in lymphocytes while this heat shock protein was detected in the 30 control children. Hsp71 levels were slightly lower in lymphocytes of patients with ITP than in controls (1567.8 ± 753.2 via 1763.2 ± 641.8 integrated optical density (IOD) units). There was a small increase of Hsp71 after recovery from ITP. The titers of plasma antibodies against Hsp60 and Hsp71 were also examined. Antibodies against Hsp71 were more common in ITP patients (15/29) than in control children (5/30). The titer of anti-Hsp71 was also higher in children patients with ITP. The prevalence of ITP children with antibodies against Hsp71 (51.7%) was as high as those with antibodies against platelet membrane glycoproteins (58.3%). CONCLUSIONS: In summary, pediatric patients with ITP showed no detectable expression of Hsp60 in lymphocytes and a high prevalence of antibody against Hsp71 in plasma. These changes add to our understanding of the pathogenesis of ITP and may be important for the diagnosis, prognosis and treatment of ITP