Mass Azithromycin Distribution and Community Microbiome: A Cluster-Randomized Trial.

BackgroundMass distributions of oral azithromycin have long been used to eliminate trachoma, and they are now being proposed to reduce childhood mortality. The observed benefit appears to be augmented with each additional treatment, suggesting a possible community-level effect. Here, we assess whether 2 biannual mass treatments of preschool children affect the community's gut microbiome at 6 months after the last distribution.MethodsIn this cluster-randomized controlled trial, children aged 1-60 months in the Dossa region of Niger were randomized at the village level to receive a single dose of azithromycin or placebo every 6 months. Fecal samples were collected 6 months after the second treatment for metagenomic deep sequencing. The prespecified primary outcome was the Euclidean PERMANOVA of the gut microbiome, or effectively the distance between the genus-level centroid at the community level, with the secondary outcome being the Simpson's α diversity.ResultsIn the azithromycin arm, the gut microbial structures were significantly different than in the placebo arm (Euclidean PERMANOVA, P < .001). Further, the diversity of the gut microbiome in the azithromycin arm was significantly lower than in the placebo arm (inverse Simpson's index, P = .005).ConclusionsTwo mass azithromycin administrations, 6 months apart, in preschool children led to long-term alterations of the gut microbiome structure and community diversity. Here, long-term microbial alterations in the community did not imply disease but were associated with an improvement in childhood mortality.Clinical trials registrationNCT02048007

Assessment of Granulovirus, Spinosad, and Mating Disruption for Controlling \u3ci\u3eCydia pomonella\u3c/i\u3e L. [Lepidoptera: Tortricidae] in Organic Coastal California Apple Orchards

Codling moth, Cydia pomonella[Lepidoptera: Tortricidae], is a major entomological pest of apples, pears, and walnuts cross the world (Pajac et al. 2016). Female codling moths lay eggs on the apple exocarp and larvae burrow within the fruit causing economic losses to fruit growers.Organic apple orchards in San Luis Obispo, CA currently have three codling moth, Cydia pomonella,control options commercially available including granulovirus (CpVG), spinosad, and mating disruption. In field tests on apple (Malus), we compare percent fruit injury between treatments of granulovirus (2.43 oz/ha Cyd-X® organically approved, Certis USA, Columbia MD), spinosad (4.05 oz/ha Entrust® Naturalyte® organically approved WP formation, Dow AgroSciences, Indianapolis IN), and a control. We also compared mating disruption in form of codling moth Codlemone® sex pheromone (257 ties/ha (506 mg)/acre Isomate®-OFM TT organically approved Pacific Biocontrol Corporation Vancouver, WA) against a control. Delta taps and 1 mg pheromone lures were used to trap males and track the degree day (DD) model for the two orchard’s codling moth populations to determine application timing for each treatment. A preliminary DD model was used based on the University of California at Davis Agricultural Extension codling moth DD model. During 2016 trialsno detectible control was provided by spray treatments with an average fruit injury of 26% control, 23% granulovirus, 28% spinosad. During 2016 trialsno detectible control was provided by mating disruption with an average fruit injury of 16% control and 16% pheromone. During 2017 trials there was detectible control provided by the treatments to the crop by both spray treatmentsand pheromone ties. 2017 average fruit injury for spray treatments was 51% control, 20% granulovirus, and 14% spinosad. 2017 average fruit injury for mating disruption was 29% control and 6% pheromone. Data suggest underlying relationship between location specific climate factors, cultivars, codling moth populations, and treatment efficacy

Diagnostics for Yaws Eradication: Insights From Direct Next-Generation Sequencing of Cutaneous Strains of Treponema pallidum.

Background: Yaws-like chronic ulcers can be caused by Treponema pallidum subspecies pertenue, Haemophilus ducreyi, or other, still-undefined bacteria. To permit accurate evaluation of yaws elimination efforts, programmatic use of molecular diagnostics is required. The accuracy and sensitivity of current tools remain unclear because our understanding of T. pallidum diversity is limited by the low number of sequenced genomes. Methods: We tested samples from patients with suspected yaws collected in the Solomon Islands and Ghana. All samples were from patients whose lesions had previously tested negative using the Centers for Disease Control and Prevention (CDC) diagnostic assay in widespread use. However, some of these patients had positive serological assays for yaws on blood. We used direct whole-genome sequencing to identify T. pallidum subsp pertenue strains missed by the current assay. Results: From 45 Solomon Islands and 27 Ghanaian samples, 11 were positive for T. pallidum DNA using the species-wide quantitative polymerase chain reaction (PCR) assay, from which we obtained 6 previously undetected T. pallidum subsp pertenue whole-genome sequences. These show that Solomon Islands sequences represent distinct T. pallidum subsp pertenue clades. These isolates were invisible to the CDC diagnostic PCR assay, due to sequence variation in the primer binding site. Conclusions: Our data double the number of published T. pallidum subsp pertenue genomes. We show that Solomon Islands strains are undetectable by the PCR used in many studies and by health ministries. This assay is therefore not adequate for the eradication program. Next-generation genome sequence data are essential for these efforts

Transcription of TP0126, Treponema pallidum Putative OmpW Homolog, Is Regulated by the Length of a Homopolymeric Guanosine Repeat

An effective mechanism for introduction of phenotypic diversity within a bacterial population exploits changes in the length of repetitive DNA elements located within gene promoters. This phenomenon, known as phase variation, causes rapid activation or silencing of gene expression and fosters bacterial adaptation to new or changing environments. Phase variation often occurs in surface-exposed proteins, and in Treponema pallidum subsp. pallidum, the syphilis agent, it was reported to affect transcription of three putative outer membrane protein (OMP)-encoding genes. When the T. pallidum subsp. pallidum Nichols strain genome was initially annotated, the TP0126 open reading frame was predicted to include a poly(G) tract and did not appear to have a predicted signal sequence that might suggest the possibility of its being an OMP. Here we show that the initial annotation was incorrect, that this poly(G) is instead located within the TP0126 promoter, and that it varies in length in vivo during experimental syphilis. Additionally, we show that TP0126 transcription is affected by changes in the poly(G) length consistent with regulation by phase variation. In silico analysis of the TP0126 open reading frame based on the experimentally identified transcriptional start site shortens this hypothetical protein by 69 amino acids, reveals a predicted cleavable signal peptide, and suggests structural homology with the OmpW family of porins. Circular dichroism of recombinant TP0126 supports structural homology to OmpW. Together with the evidence that TP0126 is fully conserved among T. pallidum subspecies and strains, these data suggest an important role for TP0126 in T. pallidum biology and syphilis pathogenesis

Effectiveness of single-dose azithromycin to treat latent yaws: a longitudinal comparative cohort study

BACKGROUND: Treatment of latent yaws is a crucial component of the WHO yaws eradication strategy to prevent relapse and the resulting transmission to uninfected children. We assessed the effectiveness of single-dose azithromycin to treat patients with latent yaws. METHODS: This population-based cohort study included children (age <20 years) living on Lihir Island, Papua New Guinea, with high-titre (rapid plasma reagin titre >/=1:8) latent or active yaws, between April, 2013, and May, 2015. Latent yaws was defined as lack of suspicious skin lesions or presence of ulcers negative for Treponema pallidum subsp pertenue on PCR, and active yaws was defined as ulcers positive for T pertenue on PCR. All children received one oral dose of 30 mg/kg azithromycin. The primary endpoint was serological cure, defined as a two-dilution decrease in rapid plasma reagin titre by 24 months after treatment. Treatment of latent yaws was taken to be non-inferior to that of active yaws if the lower limit of the two-sided 95% CI for the difference in rates was higher than or equal to -10%. This study is registered with ClinicalTrials.gov, number NCT01955252. FINDINGS: Of 311 participants enrolled, 273 (88%; 165 with latent yaws and 108 with active yaws) completed follow-up. The primary endpoint was achieved in 151 (92%) participants with latent yaws and 101 (94%) with active yaws (risk difference -2.0%, 95% CI -8.3 to 4.3), meeting the prespecified criteria for non-inferiority. INTERPRETATION: On the basis of decline in serological titre, oral single-dose azithromycin was effective in participants with latent yaws. This finding supports the WHO strategy for the eradication of yaws based on mass administration of the entire endemic community irrespective of clinical status. FUNDING: Newcrest Mining Limited and ISDIN laboratories

Challenges and key research questions for yaws eradication.

Yaws is endemic in west Africa, southeast Asia, and the Pacific region. To eradicate yaws by 2020, WHO has launched a campaign of mass treatment with azithromycin. Progress has been made towards achievement of this ambitious goal, including the validation of point-of-care and molecular diagnostic tests and piloting of the strategy in several countries, including Ghana, Vanuatu, and Papua New Guinea. Gaps in knowledge need to be addressed to allow refinement of the eradication strategy. Studies exploring determinants of the spatial distribution of yaws are needed to help with the completion of baseline mapping. The finding that Haemophilus ducreyi causes lesions similar to yaws is particularly important and further work is needed to assess the effect of azithromycin on these lesions. The integration of diagnostic tests into different stages of the eradication campaign needs investigation. Finally, studies must be done to inform the optimum mass-treatment strategy for sustainable interruption of transmission

Survey of Treponemal Infections in Free-Ranging and Captive Macaques, 1999-2012.

Survey results showed treponemal infection among pet macaques in Southeast Asia, a region with a high prevalence of human yaws. This finding, along with studies showing treponemal infection in nonhuman primates in Africa, should encourage a One Health approach to yaws eradication and surveillance activities, possibly including monitoring of nonhuman primates in yaws-endemic regions

Putting the Choice in Housing Choice Voucher, Pt. 3: Mapping Locations of Housing Choice Vouchers in the Chicago Region

Documents the location of vouchers by census tract in 6-county Chicago region as of June 30, 2003. The report provides a baseline to determine progress on assisting voucher holders in making moves to opportunity. To date, this report is one-of-a-kind

Developing New Elementary Climate Science Curriculum Strategies for K-12 Students at the Boise Watershed

Increasing greenhouse gas emissions are warming global temperatures at an alarming rate; this will affect the human population, including Idahoans! This project focuses on developing and implementing a climate science curriculum program within the Boise WaterShed’s Education Program. This service-learning capstone project, in collaboration with Boise WaterShed, seeks to develop interactive learning and lesson plans for K-6 students. This project builds upon existing activities in the Education program like greenhouse gas tag and other interactive learning games. Objectives for this project include implementing and assessing the efficacy of the new climate material. Survey questions will assess the effectiveness of climate education lesson material and methodologies for future data analysis. On March 16th, I am presenting a beta version of the created lesson plan at NorthStar Middle School. Pre and post-test questions will direct future improvements and will assess student’s responses and knowledge gain from the lesson