The relationship between zinc intake and growth in children aged 1-8 years: a systematic review and meta-analysis

BACKGROUND/OBJECTIVES: It is estimated that zinc deficiency affects 17% of the world's population, and because of periods of rapid growth children are at an increased risk of deficiency, which may lead to stunting. This paper presents a systematic review and meta-analysis of the randomised controlled trials (RCTs) that assess zinc intake and growth in children aged 1–8 years. This review is part of a larger systematic review by the European Micronutrient Recommendations Aligned Network of Excellence that aims to harmonise the approach to setting micronutrient requirements for optimal health in European populations (www.eurreca.org). SUBJECT/METHODS: Searches were performed of literature published up to and including December 2013 using MEDLINE, Embase and the Cochrane Library databases. Included studies were RCTs in apparently healthy child populations aged from 1 to 8 years that supplied zinc supplements either as capsules or as part of a fortified meal. Pooled meta-analyses were performed when appropriate. RESULTS: Nine studies met the inclusion criteria. We found no significant effect of zinc supplementation of between 2 weeks and 12 months duration on weight gain, height for age, weight for age, length for age, weight for height (WHZ) or WHZ scores in children aged 1–8 years. CONCLUSIONS: Many of the children in the included studies were already stunted and may have been suffering from multiple micronutrient deficiencies, and therefore zinc supplementation alone may have only a limited effect on growth

Protection from Experimental Cerebral Malaria with a Single Dose of Radiation-Attenuated, Blood-Stage Plasmodium berghei Parasites

BACKGROUND: Whole malaria parasites are highly effective in inducing immunity against malaria. Due to the limited success of subunit based vaccines in clinical studies, there has been a renewed interest in whole parasite-based malaria vaccines. Apart from attenuated sporozoites, there have also been efforts to use live asexual stage parasites as vaccine immunogens. METHODOLOGY AND RESULTS: We used radiation exposure to attenuate the highly virulent asexual blood stages of the murine malaria parasite P. berghei to a non-replicable, avirulent form. We tested the ability of the attenuated blood stage parasites to induce immunity to parasitemia and the symptoms of severe malaria disease. Depending on the mouse genetic background, a single high dose immunization without adjuvant protected mice from parasitemia and severe disease (CD1 mice) or from experimental cerebral malaria (ECM) (C57BL/6 mice). A low dose immunization did not protect against parasitemia or severe disease in either model after one or two immunizations. The protection from ECM was associated with a parasite specific antibody response and also with a lower level of splenic parasite-specific IFN-γ production, which is a mediator of ECM pathology in C57BL/6 mice. Surprisingly, there was no difference in the sequestration of CD8+ T cells and CD45+ CD11b+ macrophages in the brains of immunized, ECM-protected mice. CONCLUSIONS: This report further demonstrates the effectiveness of a whole parasite blood-stage vaccine in inducing immunity to malaria and explicitly demonstrates its effectiveness against ECM, the most pathogenic consequence of malaria infection. This experimental model will be important to explore the formulation of whole parasite blood-stage vaccines against malaria and to investigate the immune mechanisms that mediate protection against parasitemia and cerebral malaria

Costs of integrating HIV self-testing in public health facilities in Malawi, South Africa, Zambia and Zimbabwe.

INTRODUCTION: As countries approach the UNAIDS 95-95-95 targets, there is a need for innovative and cost-saving HIV testing approaches that can increase testing coverage in hard-to-reach populations. The HIV Self-Testing Africa-Initiative distributed HIV self-test (HIVST) kits using unincentivised HIV testing counsellors across 31 public facilities in Malawi, South Africa, Zambia and Zimbabwe. HIVST was distributed either through secondary (partner's use) distribution alone or primary (own use) and secondary distribution approaches. METHODS: We evaluated the costs of adding HIVST to existing HIV testing from the providers' perspective in the 31 public health facilities across the four countries between 2018 and 2019. We combined expenditure analysis and bottom-up costing approaches. We also carried out time-and-motion studies on the counsellors to estimate the human resource costs of introducing and demonstrating how to use HIVST for primary and secondary use. RESULTS: A total of 41 720 kits were distributed during the analysis period, ranging from 1254 in Zimbabwe to 27 678 in Zambia. The cost per kit distributed through the primary distribution approach was $4.27 in Zambia and$9.24 in Zimbabwe. The cost per kit distributed through the secondary distribution approach ranged from $6.46 in Zambia to$13.42 in South Africa, with a wider variation in the average cost at facility-level. From the time-and-motion observations, the counsellors spent between 20% and 44% of the observed workday on HIVST. Overall, personnel and test kit costs were the main cost drivers. CONCLUSION: The average costs of distributing HIVST kits were comparable across the four countries in our analysis despite wide cost variability within countries. We recommend context-specific exploration of potential efficiency gains from these facility-level cost variations and demand creation activities to ensure continued affordability at scale

Pathogenic Roles of CD14, Galectin-3, and OX40 during Experimental Cerebral Malaria in Mice

An in-depth knowledge of the host molecules and biological pathways that contribute towards the pathogenesis of cerebral malaria would help guide the development of novel prognostics and therapeutics. Genome-wide transcriptional profiling of the brain tissue during experimental cerebral malaria (ECM ) caused by Plasmodium berghei ANKA parasites in mice, a well established surrogate of human cerebral malaria, has been useful in predicting the functional classes of genes involved and pathways altered during the course of disease. To further understand the contribution of individual genes to the pathogenesis of ECM, we examined the biological relevance of three molecules – CD14, galectin-3, and OX40 that were previously shown to be overexpressed during ECM. We find that CD14 plays a predominant role in the induction of ECM and regulation of parasite density; deletion of the CD14 gene not only prevented the onset of disease in a majority of susceptible mice (only 21% of CD14-deficient compared to 80% of wildtype mice developed ECM, p<0.0004) but also had an ameliorating effect on parasitemia (a 2 fold reduction during the cerebral phase). Furthermore, deletion of the galectin-3 gene in susceptible C57BL/6 mice resulted in partial protection from ECM (47% of galectin-3-deficient versus 93% of wildtype mice developed ECM, p<0.0073). Subsequent adherence assays suggest that galectin-3 induced pathogenesis of ECM is not mediated by the recognition and binding of galectin-3 to P. berghei ANKA parasites. A previous study of ECM has demonstrated that brain infiltrating T cells are strongly activated and are CD44+CD62L− differentiated memory T cells [1]. We find that OX40, a marker of both T cell activation and memory, is selectively upregulated in the brain during ECM and its distribution among CD4+ and CD8+ T cells accumulated in the brain vasculature is approximately equal

The Columbia River Channel Deepening Project Balancing the Decision Using a Hierarchical Decision Model (HDM)

The Columbia River Channel Deepening Project (CRCD) currently under consideration by the U.S. Army Corps of Engineers (Corps) would be the one of the largest federally funded public works projects in Oregon over the next decade, with a range of development costs between $150 and$200 million. The focus of the project is to increase the depth of the Columbia River to not less than 43 feet, such that larger loads of cargo may be exported from the Port of Portland to the Pacific Ocean. Thus, it will contribute to the larger goal of creating more export opportunities for the southwest Washington and Central Oregon markets of goods and services. The CRCD project is one that has generated many newspaper headlines, controversy and analysis by many interested parties over its ten year development process. It is an entity of great interest for decision makers in the engineering community as well, and as such, Team 1 identified this project as ripe for applying decision making course tools. Note: The presentation associated with this report is included here as a supplemental file

Changes in flagellin glycosylation affect Campylobacter autoagglutination and virulence.: Mol.Microbiology

NRC publication: Ye

Molecular Correlates of Experimental Cerebral Malaria Detectable in Whole Blood ▿ †

Cerebral malaria (CM) is a primary cause of deaths caused by Plasmodium falciparum in young children in sub-Saharan Africa. Laboratory tests based on early detection of host biomarkers in patient blood would help in the prognosis and differential diagnosis of CM. Using the Plasmodium berghei ANKA murine model of experimental cerebral malaria (ECM), we have identified over 300 putative diagnostic biomarkers of ECM in the circulation by comparing the whole-blood transcriptional profiles of resistant mice (BALB/c) to those of two susceptible strains (C57BL/6 and CBA/CaJ). Our results suggest that the transcriptional profile of whole blood captures the molecular and immunological events associated with the pathogenesis of disease. We find that during ECM, erythropoiesis is dysfunctional, thrombocytopenia is evident, and glycosylation of cell surface components may be modified. Furthermore, analysis of immunity-related genes suggests that slightly distinct mechanisms of immunopathogenesis may operate in susceptible C57BL/6 and CBA/CaJ mice. Furthermore, our data set has allowed us to create a molecular signature of ECM composed of a subset of circulatory markers. Complement component C1q, β-chain, nonspecific cytotoxic cell receptor protein 1, prostate stem cell antigen, DnaJC, member 15, glutathione S-transferase omega-1, and thymidine kinase 1 were overexpressed in blood during the symptomatic phase of ECM, as measured by quantitative real-time PCR analysis. These studies provide the first host transcriptome database that is uniquely altered during the pathogenesis of ECM in blood. A subset of these mediators of ECM warrant validation in P. falciparum-infected young African children as diagnostic markers of CM