Medium-term seed storage of 50 genera of forage legumes and evidence-based genebank monitoring intervals

Genebanks maintaining seeds for long-term genetic resources conservation monitor seed lots to detect early loss in viability. Monitoring is costly and depletes valuable seed. Three decades of genebank seed germination test results of diverse forage species from 50 legume genera in the International Livestock Research Institute’s medium-term store (circa 8° C with 5 % moisture content) were analysed to determine whether advice on seed monitoring intervals could be derived. Cumulative normal distributions were fitted by probit analysis for each seed lot and compared within each genus. Six patterns of within-genus variation were identified: no detectable trend in germination test results during storage (4 genera); detectable trends, but variable (positive to negative) amongst lots (5); consistent slope of loss in viability amongst lots (17); consistent slope of increase in ability to germinate amongst lots (21); common loss in viability amongst lots (2); common increase in ability to germinate amongst lots (1). Seed lot monitoring intervals for the medium-term store were derived for each of 19 genera with consistent loss in viability across seed lots: three genera provided comparatively rapid deterioration, five met the general expectations for a medium-term store (2-10 years’ maintenance of high viability), whilst 11 provided much better survival. Moreover, 26 further genera provided no evidence as yet of seed deterioration; of these, 22 improved in ability to germinate during storage indicating confounding of hardseededness with viability in germination tests

Do intracerebral cytokine responses explain the harmful effects of dexamethasone in HIV-associated cryptococcal meningitis?

Background The CryptoDex trial showed dexamethasone was associated with poorer clinical outcomes and slower fungal clearance in HIV-associated cryptococcal meningitis. We analysed CSF cytokine concentrations from CrytpoDex participants over the first week of treatment to investigate potential mechanisms of harm and test two hypotheses: dexamethasone reduced pro-inflammatory cytokine concentrations leading to poorer outcomes; and leukotriene A4 hydrolase (LTA4H) genotype (previously associated with dexamethasone responsiveness in tuberculous meningitis) influenced dexamethasone’s clinical impact. Methods We included participants from Vietnam, Thailand, and Uganda. We measured CSF concentrations of IFN-γ, TNF-α, GM-CSF, IL-6, IL-12p70, IL-8, MCP-1, MIP-1α, IL-4, IL-10, and IL-17 from days 1 to 7 of treatment using the Luminex system. We determined LTA4H genotype using a TaqMan genotyping assay of the promoter region SNP rs17525495. We assessed the impact of dexamethasone on cytokine concentration dynamics and the association between cytokine concentration dynamics and fungal clearance with mixed effect models. We measure the influence of LTA4H genotype on outcomes with Cox regression models. Results Dexamethasone increased the rate of TNF-α concentration decline (-0.13 pg/ml/day (95%CI -0.22 to -0.06) p=0.03), which was associated with slower fungal clearance (correlation -0.62 (-0.83 to -0.26)). LTA4H genotype had no statistically significant impact on outcome or response to dexamethasone therapy. Better clinical outcomes were associated with higher baseline concentrations of IFN-γ. Conclusions Dexamethasone may slow fungal clearance and worsen outcomes by increasing the rate of decline of TNF-α concentration

Clinical features, antimicrobial susceptibility patterns and genomics of bacteria causing neonatal sepsis in a children's hospital in Vietnam: protocol for a prospective observational study.

INTRODUCTION: The clinical syndrome of neonatal sepsis, comprising signs of infection, septic shock and organ dysfunction in infants ≤4 weeks of age, is a frequent sequel to bloodstream infection and mandates urgent antimicrobial therapy. Bacterial characterisation and antimicrobial susceptibility testing is vital for ensuring appropriate therapy, as high rates of antimicrobial resistance (AMR), especially in low-income and middle-income countries, may adversely affect outcome. Ho Chi Minh City (HCMC) in Vietnam is a rapidly expanding city in Southeast Asia with a current population of almost 8 million. There are limited contemporary data on the causes of neonatal sepsis in Vietnam, and we hypothesise that the emergence of multidrug resistant bacteria is an increasing problem for the appropriate management of sepsis cases. In this study, we aim to investigate the major causes of neonatal sepsis and assess disease outcomes by clinical features, antimicrobial susceptibility profiles and genome composition. METHOD AND ANALYSIS: We will conduct a prospective observational study to characterise the clinical and microbiological features of neonatal sepsis in a major children's hospital in HCMC. All bacteria isolated from blood subjected to whole genome sequencing. We will compare clinical variables and outcomes between different bacterial species, genome composition and AMR gene content. AMR gene content will be assessed and stratified by species, years and contributing hospital departments. Genome sequences will be analysed to investigate phylogenetic relationships. ETHICS AND DISSEMINATION: The study will be conducted in accordance with the principles of the Declaration of Helsinki and the International Council on Harmonization Guidelines for Good Clinical Practice. Ethics approval has been provided by the Oxford Tropical Research Ethics Committee 35-16 and Vietnam Children's Hospital 1 Ethics Committee 73/GCN/BVND1. The findings will be disseminated at international conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN69124914; Pre-results

Three phylogenetic groups have driven the recent population expansion of Cryptococcus neoformans

Cryptococcus neoformans (C. neoformans var. grubii) is an environmentally acquired pathogen causing 181,000 HIV-associated deaths each year. We sequenced 699 isolates, primarily C. neoformans from HIV-infected patients, from 5 countries in Asia and Africa. The phylogeny of C. neoformans reveals a recent exponential population expansion, consistent with the increase in the number of susceptible hosts. In our study population, this expansion has been driven by three sub-clades of the C. neoformans VNIa lineage; VNIa-4, VNIa-5 and VNIa-93. These three sub-clades account for 91% of clinical isolates sequenced in our study. Combining the genome data with clinical information, we find that the VNIa-93 sub-clade, the most common sub-clade in Uganda and Malawi, was associated with better outcomes than VNIa-4 and VNIa-5, which predominate in Southeast Asia. This study lays the foundation for further work investigating the dominance of VNIa-4, VNIa-5 and VNIa-93 and the association between lineage and clinical phenotype

Reproductive performance in sows in relation to Japanese Encephalitis Virus seropositivity in an endemic area

Japanese Encephalitis Virus (JEV) is considered an important reproductive pathogen in pigs. Most studies of the reproductive impact of JEV have been conducted in areas where the disease occurs in seasonal epidemics. In this study, the associations between seropositivity for JEV, measured with an IgG ELISA, and the number of piglets born alive and stillborn were investigated in a tropical area endemic for JEV in Vietnam. Sixty percent of sows from four farms in the Mekong delta of Vietnam were seropositive to JEV and the Odds Ratio for a sow being infected was highest (6.4) in sows above 3.5 years (95% confidence interval 2.2–18.3). There was an association between increasing Optical Density (OD) values from the ELISA and the number of stillborn piglets in sows less than 1.5 years, but no effect of seropositivity could be shown when all sows were studied. OD values had an effect (p = 0.04) on the number of piglets born alive in the statistical analysis only when interacting with the effect of the breeds. An increase in mean OD value of the herd was correlated (p < 0.0001) with an increase in the number of piglets born alive. In this study, there was evidence of a negative association between seropositivity for JEV and the reproductive performance only in sows less than 1.5 years in endemic areas. This could be explained by a year-round infection with the virus, which would lead to immunity in many gilts before their first pregnancy. This, in turn, may imply that JEV infection in pigs is of minor importance for the reproductive performance in endemic areas

Nationwide Investigation of the Pyrethroid Susceptibility of Mosquito Larvae Collected from Used Tires in Vietnam

Pyrethroid resistance is envisioned to be a major problem for the vector control program since, at present, there are no suitable chemical substitutes for pyrethroids. Cross-resistance to knockdown agents, which are mainly used in mosquito coils and related products as spatial repellents, is the most serious concern. Since cross-resistance is a global phenomenon, we have started to monitor the distribution of mosquito resistance to pyrethroids. The first pilot study was carried out in Vietnam. We periodically drove along the national road from the north end to the Mekong Delta in Vietnam and collected mosquito larvae from used tires. Simplified susceptibility tests were performed using the fourth instar larvae of Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus. Compared with the other species, Ae. aegypti demonstrated the most prominent reduction in susceptibility. For Ae. aegypti, significant increases in the susceptibility indices with a decrease in the latitude of collection points were observed, indicating that the susceptibility of Ae. aegypti against d-allethrin was lower in the southern part, including mountainous areas, as compared to that in the northern part of Vietnam. There was a significant correlation between the susceptibility indices in Ae. aegypti and the sum of annual pyrethroid use for malaria control (1998–2002). This might explain that the use of pyrethroids as residual treatment inside houses and pyrethroid-impregnated bed nets for malaria control is attributable to low pyrethroid susceptibility in Ae. aegypti. Such insecticide treatment appeared to have been intensively administered in the interior and along the periphery of human habitation areas where, incidentally, the breeding and resting sites of Ae. aegypti are located. This might account for the strong selection pressure toward Ae. aegypti and not Ae. albopictus

Distribution Systems of Insecticide-Treated Bed Nets for Malaria Control in Rural Burkina Faso: Cluster-Randomized Controlled Trial

BACKGROUND: Insecticide-impregnated bed nets (ITNs) have been shown to be a highly effective tool against malaria in the endemic regions of sub-Saharan Africa (SSA). There are however different opinions about the role of ITN social marketing and ITN free distribution in the roll-out of ITN programmes. The objective of this study was to evaluate the effects of free ITN distribution through antenatal care services in addition to an ITN social marketing programme in an area typical for rural SSA. METHODS: A cluster-randomised controlled ITN trial took place in the whole Kossi Province in north-western Burkina Faso, an area highly endemic for malaria. Twelve clusters were assigned to long-term ITN (Serena brand) social marketing plus free ITN (Serena brand) distribution to all pregnant women attending governmental antenatal care services (group A), and 13 clusters to ITN social marketing only (group B). The intervention took place during the rainy season of 2006 and thereafter. The trial was evaluated through a representative household survey at baseline and after one year. Serena ITN household ownership was the primary outcome measure. FINDINGS: A total of 1052 households were visited at baseline in February 2006 and 1050 at follow-up in February 2007. Overall Serena ITN household ownership increased from 16% to 28% over the study period, with a significantly higher increase in group A (13% to 35%) than in group B (18% to 23%) (p<0.001). INTERPRETATION: The free distribution of ITNs to pregnant women through governmental antenatal care services in addition to ITN social marketing substantially improved ITN household ownership in rural Burkina Faso. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN07985309