Heterogeneity in the spread and control of infectious disease: consequences for the elimination of canine rabies

Understanding the factors influencing vaccination campaign effectiveness is vital in designing efficient disease elimination programmes. We investigated the importance of spatial heterogeneity in vaccination coverage and human-mediated dog movements for the elimination of endemic canine rabies by mass dog vaccination in Region VI of the Philippines (Western Visayas). Household survey data was used to parameterise a spatially-explicit rabies transmission model with realistic dog movement and vaccination coverage scenarios, assuming a basic reproduction number for rabies drawn from the literature. This showed that heterogeneous vaccination reduces elimination prospects relative to homogeneous vaccination at the same overall level. Had the three vaccination campaigns completed in Region VI in 2010–2012 been homogeneous, they would have eliminated rabies with high probability. However, given the observed heterogeneity, three further campaigns may be required to achieve elimination with probability 0.95. We recommend that heterogeneity be reduced in future campaigns through targeted efforts in low coverage areas, even at the expense of reduced coverage in previously high coverage areas. Reported human-mediated dog movements did not reduce elimination probability, so expending limited resources on restricting dog movements is unnecessary in this endemic setting. Enhanced surveillance will be necessary post-elimination, however, given the reintroduction risk from long-distance dog movements

High levels of childhood obesity observed among 3- to 7-year-old New Zealand Pacific children is a public health concern.

This cross-sectional, community-based survey was designed to assess attained growth and body composition of 3- to 7-y-old Pacific children (n = 21 boys and 20 girls) living in Dunedin, New Zealand, and to examine nondietary factors associated with the percentage of body fat. Fat mass, lean tissue mass and the percentage of body fat were measured using dual energy X-ray absorptiometry. One trained anthropometrist also measured height, weight, skinfolds (triceps, subscapular) and circumferences (mid-upper arm, chest, waist, calf). Compared with the National Center for Health Statistics and National Health and Examination Surveys I and II reference data, these Pacific children were tall and heavy for their age with high arm-muscle-area-for-height. Median (quartiles) Z-scores for height and BMI-for-age and arm-muscle-area-for-height were 1.33 (0.60, 2.15), 1.20 (0.74, 4.43) and 1.09 (0.63, 1.85), respectively. Their median (quartile) percentage of body fat was 21.8% (15.0, 35.5) of which 38.5% was located in the trunk. The estimated percentage of children classified as obese ranged from 34 to 49% depending on the criterion used. Over 60% of the children had levels of trunk fat above 1 SD of reported age- and sex-specific Z-scores for New Zealand children. The nondietary factors examined (hours of television viewing and hours playing organized sports, as reported by parents) were not associated with variations in the percentage of body fat, after adjusting for age, sex and birth weight. These extremely high levels of obesity and truncal fat among very young New Zealand children will have major public health implications as these children age

Alginate oligosaccharides enhance diffusion and activity of colistin in a mucin-rich environment

In a number of chronic respiratory diseases e.g. cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), the production of viscous mucin reduces pulmonary function and represents an effective barrier to diffusion of inhaled therapies e.g. antibiotics. Here, a 2-compartment Transwell model was developed to study impaired diffusion of the antibiotic colistin across an artificial sputum (AS) matrix/medium and to quantify its antimicrobial activity against Pseudomonas aeruginosa NH57388A biofilms (alone and in combination with mucolytic therapy). High-performance liquid chromatography coupled with fluorescence detection (HPLC-FLD) revealed that the presence of AS medium significantly reduced the rate of colistin diffusion (> 85% at 48 h; p < 0.05). Addition of alginate oligosaccharide (OligoG CF-5/20) significantly improved colistin diffusion by 3.7 times through mucin-rich AS medium (at 48 h; p < 0.05). Increased diffusion of colistin with OligoG CF-5/20 was shown (using confocal laser scanning microscopy and COMSTAT image analysis) to be associated with significantly increased bacterial killing (p < 0.05). These data support the use of this model to study drug and small molecule delivery across clinically-relevant diffusion barriers. The findings indicate the significant loss of colistin and reduced effectiveness that occurs with mucin binding, and support the use of mucolytics to improve antimicrobial efficacy and lower antibiotic exposure

The availability and geographic location of open-source food composition data used to estimate micronutrient intakes in sub-Saharan Africa: A scoping review

BACKGROUND: Estimates of dietary micronutrient intakes rely on food composition data. The nutrient composition of foods varies spatially with potentially large effects on dietary micronutrient intakes. This review assessed the availability and geographic origin of five minerals (calcium, iron, iodine, selenium and zinc) in publicly available food composition tables/databases (FCTs) for use in sub-Saharan Africa (SSA). METHODS: A scoping review was conducted following PRISMA guidelines, in which four databases (MEDLINE, Embase, Global Health and Africa Wide Information) and four online resources were searched to identify published FCTs for use in SSA. Metadata were reviewed to identify the geographic origin of composition values for selected foods. RESULTS: Nineteen publicly available FCTs were identified, with the highest geographic coverage in Eastern Africa (45% of countries) and lowest coverage in Central Africa (12% of countries). Iodine and selenium were reported in four and six FCTs, respectively, while iron and calcium were included in ≥ 18 FCTs. More than 60% of nutrient values were borrowed from other FCTs. The geographic origin of 22% of mineral values were documented. CONCLUSIONS: Limited local food composition analytical data is available, for estimating mineral intakes of SSA populations, with poor documentation of the data sources and the geographic origins of samples. New data structures and improved metadata are required to capture and report geographic information in publicly available FCTs, and to accommodate a new generation of spatially-resolved food composition data

Bi-functional alginate oligosaccharide–polymyxin conjugates for improved treatment of multidrug-resistant gram-negative bacterial infections

The recent emergence of resistance to colistin, an antibiotic of last resort with dose-limiting toxicity, has highlighted the need for alternative approaches to combat infection. This study aimed to generate and characterise alginate oligosaccharide (“OligoG”)–polymyxin (polymyxin B and E (colistin)) conjugates to improve the effectiveness of these antibiotics. OligoG–polymyxin conjugates (amide- or ester-linked), with molecular weights of 5200–12,800 g/mol and antibiotic loading of 6.1–12.9% w/w, were reproducibly synthesised. In vitro inflammatory cytokine production (tumour necrosis factor alpha (TNFα) ELISA) and cytotoxicity (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) of colistin (2.2–9.3-fold) and polymyxin B (2.9–27.2-fold) were significantly decreased by OligoG conjugation. Antimicrobial susceptibility tests (minimum inhibitory concentration (MIC), growth curves) demonstrated similar antimicrobial efficacy of ester- and amide-linked conjugates to that of the parent antibiotic but with more sustained inhibition of bacterial growth. OligoG–polymyxin conjugates exhibited improved selectivity for Gram-negative bacteria in comparison to mammalian cells (approximately 2–4-fold). Both OligoG–colistin conjugates caused significant disruption of Pseudomonas aeruginosa biofilm formation and induced bacterial death (confocal laser scanning microscopy). When conjugates were tested in an in vitro “time-to-kill” (TTK) model using Acinetobacter baumannii, only ester-linked conjugates reduced viable bacterial counts (~2-fold) after 4 h. Bi-functional OligoG–polymyxin conjugates have potential therapeutic benefits in the treatment of multidrug-resistant (MDR) Gram-negative bacterial infections, directly reducing toxicity whilst retaining antimicrobial and antibiofilm activities

Systematic review of metrics used to characterise dietary nutrient supply from household consumption and expenditure surveys.

OBJECTIVE: To review existing publications using Household Consumption and Expenditure Survey (HCES) data to estimate household dietary nutrient supply to (1) describe scope of available literature, (2) identify the metrics reported and parameters used to construct these metrics, (3) summarise comparisons between estimates derived from HCES and individual dietary assessment data and (4) explore the demographic and socio-economic sub-groups used to characterise risks of nutrient inadequacy. DESIGN: This study is a systematic review of publications identified from online databases published between 2000 to 2019 that used HCES food consumption data to estimate household dietary nutrient supply. Further publications were identified by 'snowballing' the references of included database-identified publications. SETTING: Publications using data from low- and lower-middle income countries. RESULTS: In total, fifty-eight publications were included. Three metrics were reported that characterised household dietary nutrient supply: apparent nutrient intake per adult-male equivalent per day (n 35), apparent nutrient intake per capita per day (n 24) and nutrient density (n 5). Nutrient intakes were generally overestimated using HCES food consumption data, with several studies finding sizeable discrepancies compared with intake estimates based on individual dietary assessment methods. Sub-group analyses predominantly focused on measuring variation in household dietary nutrient supply according to socio-economic position and geography. CONCLUSION: HCES data are increasingly being used to assess diets across populations. More research is needed to inform the development of a framework to guide the use of and qualified interpretation of dietary assessments based on these data

Vitamin B 12 and Folate status of older New Zealand women

The primary aim of this study was to assess the biochemical vitamin B 12 and folate status of a representative group of elderly women (70-80 y) living in Dunedin, New Zealand. A second aim was to determine the prevalence of hyperhomocysteinaemia and to explore the determinants of homocysteine (hcy) concentration in this population. A cross-sectional study was carried out between June and August of 2000. Two hundred and fifty women were randomly selected from the 1998 electoral roll. Fasting blood samples were analysed for folate, vitamin B 12 , total hcy, creatinine, and haematological parameters. Of the women selected, 87 did not respond, 37 were not traceable, 23 were not eligible or had died, and 103 agreed to participate. The overall response rate was 46%. Based on a cut-off of 150 pmol/L for serum B 12 , 13 % of participants would be classified as having sub-optimal vitamin B 12 status. Of the women, 3 and 5 %, respectively, had low serum (&lt;6.6 nmol/L) and erythrocyte folate (&lt;317 nmol/L) concentrations. No participant had megaloblastic anaemia. The prevalence of hyperhomocysteinaemia (&gt;15 µmol/L) in this population was 18%. Hyperhomocysteinaemia in this group may be partly explained by renal insufficiency because there was a significant association between serum creatinine and plasma hcy (P&lt;0.001). Blood folate levels but not serum B 12 were significantly inversely associated with hcy. In conclusion, there was a moderately high prevalence of hyperhomocysteinaemia and suboptimal plasma vitamin B 12 concentrations but not low blood folate concentrations in this elderly female population

Can selenium deficiency in Malawi be alleviated through consumption of agro-biofortified maize flour? Study protocol for a randomised, double-blind, controlled trial

Micronutrient deficiencies including selenium (Se) are widespread in Malawi and potentially underlie a substantial disease burden, particularly among poorer and marginalised populations. Concentrations of Se in staple cereal crops can be increased through application of Se fertilisers – a process known as agronomic biofortification (agro-biofortification) – and this may contribute to alleviating deficiencies. The Addressing Hidden Hunger with Agronomy (AHHA) trial aims to establish the efficacy of this approach for improving Se status in rural Malawi

Modeling food fortification contributions to micronutrient requirements in Malawi using Household Consumption and Expenditure Surveys.

Large-scale food fortification may be a cost-effective intervention to increase micronutrient supplies in the food system when implemented under appropriate conditions, yet it is unclear if current strategies can equitably benefit populations with the greatest micronutrient needs. This study developed a mathematical modeling framework for comparing fortification scenarios across different contexts. It was applied to model the potential contributions of three fortification vehicles (oil, sugar, and wheat flour) toward meeting dietary micronutrient requirements in Malawi through secondary data analyses of a Household Consumption and Expenditure Survey. We estimated fortification vehicle coverage, micronutrient density of the diet, and apparent intake of nonpregnant, nonlactating women for nine different micronutrients, under three food fortification scenarios and stratified by subpopulations across seasons. Oil and sugar had high coverage and apparent consumption that, when combined, were predicted to improve the vitamin A adequacy of the diet. Wheat flour contributed little to estimated dietary micronutrient supplies due to low apparent consumption. Potential contributions of all fortification vehicles were low in rural populations of the lowest socioeconomic position. While the model predicted large-scale food fortification would contribute to reducing vitamin A inadequacies, other interventions are necessary to meet other micronutrient requirements, especially for the rural poor

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN