On the path to rabies elimination: The need for risk assessments to improve administration of post-exposure prophylaxis.

Costs of rabies post-exposure prophylaxis (PEP) often remain high in regions where rabies has been controlled in dogs, presenting a challenge for sustaining rabies elimination programmes. We investigated the potential for bite patient risk assessments to improve PEP provision and surveillance in settings approaching elimination of dog-mediated rabies. We conducted a longitudinal study of patients presenting to animal bite treatment centres (ABTCs) on the island province of Bohol in the Philippines to investigate the health status of biting dogs and to quantify current expenditure on PEP. Incidence of bite patients presenting to ABTCs was high (>300/100,000 persons/year) and increasing, resulting in substantial health provider costs. Over $142,000 was spent on PEP in 2013 for a population of 1.3 million. From follow up of 3820 bite patients we found that  >92% were bitten by healthy dogs (alive 14 days after the bite) and just 1.4% were bitten by probable or confirmed rabid dogs. The status of dogs that bit 6% of patients could not be determined. During the course of investigations of bites by suspect dogs, we were able to obtain samples for case confirmation, identify exposed persons who had not sought PEP as well as in-contact dogs at risk of developing rabies. We calculate that expenditure on PEP could at least be halved through more judicious approaches to provision of PEP, based on the histories of biting animals determined through risk assessments with bite patients. We conclude that a One Health approach to surveillance based on Integrated Bite Case Management could improve the sustainability and effectiveness of rabies elimination programmes while also improving patient care by identifying those genuinely in need of lifesaving PEP

The AWED trial (Applying Wolbachia to Eliminate Dengue) to assess the efficacy of Wolbachia-infected mosquito deployments to reduce dengue incidence in Yogyakarta, Indonesia: study protocol for a cluster randomised controlled trial.

BACKGROUND: Dengue and other arboviruses transmitted by Aedes aegypti mosquitoes, including Zika and chikungunya, present an increasing public health challenge in tropical regions. Current vector control strategies have failed to curb disease transmission, but continue to be employed despite the absence of robust evidence for their effectiveness or optimal implementation. The World Mosquito Program has developed a novel approach to arbovirus control using Ae. aegypti stably transfected with Wolbachia bacterium, with a significantly reduced ability to transmit dengue, Zika and chikungunya in laboratory experiments. Modelling predicts this will translate to local elimination of dengue in most epidemiological settings. This study protocol describes the first trial to measure the efficacy of Wolbachia in reducing dengue virus transmission in the field. METHODS/DESIGN: The study is a parallel, two-arm, non-blinded cluster randomised controlled trial conducted in a single site in Yogyakarta, Indonesia. The aim is to determine whether large-scale deployment of Wolbachia-infected Ae. aegypti mosquitoes leads to a measurable reduction in dengue incidence in treated versus untreated areas. The primary endpoint is symptomatic, virologically confirmed dengue virus infection of any severity. The 26 km2 study area was subdivided into 24 contiguous clusters, allocated randomly 1:1 to receive Wolbachia deployments or no intervention. We use a novel epidemiological study design, the cluster-randomised test-negative design trial, in which dengue cases and arbovirus-negative controls are sampled concurrently from among febrile patients presenting to a network of primary care clinics, with case or control status classified retrospectively based on the results of laboratory diagnostic testing. Efficacy is estimated from the odds ratio of Wolbachia exposure distribution (probability of living in a Wolbachia-treated area) among virologically confirmed dengue cases compared to test-negative controls. A secondary per-protocol analysis allows for individual Wolbachia exposure levels to be assessed to account for movements outside the cluster and the heterogeneity in local Wolbachia prevalence among treated clusters. DISCUSSION: The findings from this study will provide the first experimental evidence for the efficacy of Wolbachia in reducing dengue incidence. Together with observational evidence that is accumulating from pragmatic deployments of Wolbachia in other field sites, this will provide valuable data to estimate the effectiveness of this novel approach to arbovirus control, inform future cost-effectiveness estimates, and guide plans for large-scale deployments in other endemic settings. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT03055585 . Registered on 14 February 2017

An Anomalous Type IV Secretion System in Rickettsia Is Evolutionarily Conserved

Bacterial type IV secretion systems (T4SSs) comprise a diverse transporter family functioning in conjugation, competence, and effector molecule (DNA and/or protein) translocation. Thirteen genome sequences from Rickettsia, obligate intracellular symbionts/pathogens of a wide range of eukaryotes, have revealed a reduced T4SS relative to the Agrobacterium tumefaciens archetype (vir). However, the Rickettsia T4SS has not been functionally characterized for its role in symbiosis/virulence, and none of its substrates are known.Superimposition of T4SS structural/functional information over previously identified Rickettsia components implicate a functional Rickettsia T4SS. virB4, virB8 and virB9 are duplicated, yet only one copy of each has the conserved features of similar genes in other T4SSs. An extraordinarily duplicated VirB6 gene encodes five hydrophobic proteins conserved only in a short region known to be involved in DNA transfer in A. tumefaciens. virB1, virB2 and virB7 are newly identified, revealing a Rickettsia T4SS lacking only virB5 relative to the vir archetype. Phylogeny estimation suggests vertical inheritance of all components, despite gene rearrangements into an archipelago of five islets. Similarities of Rickettsia VirB7/VirB9 to ComB7/ComB9 proteins of epsilon-proteobacteria, as well as phylogenetic affinities to the Legionella lvh T4SS, imply the Rickettsiales ancestor acquired a vir-like locus from distantly related bacteria, perhaps while residing in a protozoan host. Modern modifications of these systems likely reflect diversification with various eukaryotic host cells.We present the rvh (Rickettsiales vir homolog) T4SS, an evolutionary conserved transporter with an unknown role in rickettsial biology. This work lays the foundation for future laboratory characterization of this system, and also identifies the Legionella lvh T4SS as a suitable genetic model

Peranan Media Massa Dalam Meningkatkan Pengetahuan Politik Mahasiswa

ABSTRAKPenelitian ini akan mengkaji tentang bagaimana peranan media masa dalam meningkatkan pengetahuan politik mahasiswa. Dengan menggunakan metode kualitatif (Sugiyono, 2019) penelitian ini akan fokus untuk mengetahui bagaimana pengaruh pemanfaatan informasi melalui media massa terhadap pemahaman dan pengetahuan politik mahasiswa khususnya di FMIPA, Universitas Sam Ratulangi Manado, terkait dengan pemilihan walikota dan wakil walikota Kota Manado tahun 2020. Temuan penelitian mengambarkan bahwa mahasiswa FMIPA Universitas Sam Ratulangi banyak yang menggunakan media online/internet dan TV sebagai sumber informasi terkait dengan Pilwako Kota Manado tahun 2020. Media massa surat kabar cetak dan radio kurang dimanfaatkan, disebabkan karena keberadaan surat kabar online kini telah tersedia dan lebih mudah untuk diakses. Temuan penelitian juga menggambarkan bahwa peranan media massa sangat berpengaruh terhadap tingkat pemahaman dan pengetahuan mahasiswa tentang Pemilu Walikota dan Wakil Walikota di Kota Manado Tahun 2020. Kata kunci: Media Massa; Mahasiswa; Pilwako ABSTRACTThis research will examine how the role of the mass media in increasing students' political knowledge. By using a qualitative method (Sugiyono, 2019) this research will focus on finding out how the influence of the use of information through the mass media has on students' understanding and political knowledge, especially at the Faculty of Mathematics and Natural Sciences, Sam Ratulangi University, Manado, related to the election of the mayor and deputy mayor ( Pilwako) in Manado city in 2020. Research findings illustrate that many students of the Faculty of Mathematics and Natural Sciences, University of Sam Ratulangi use online/internet media and TV as a source of information related to the 2020 Manado City. The mass media of print newspapers and radio are underutilized , due to the existence of online newspapers now available and easier to access. The research findings also illustrate that the role of the mass media greatly influences the level of understanding and knowledge of students about the Mayor and Deputy Mayor Elections in Manado City in 2020. Keywords: Mass Media; Student; Pilwako &nbsp

Competition for amino acids between Wolbachia and the mosquito host, Aedes aegypti

The endosymbiont Wolbachia represents a promising method of dengue control, as it reduces the ability of the primary vector, the mosquito Aedes aegypti, to transmit viruses. When mosquitoes infected with the virulent Wolbachia strain wMelPop are fed non-human blood, there is a drastic reduction in mosquito fecundity and egg viability. Wolbachia has a reduced genome and is clearly dependent on its host for a wide range of nutritional needs. The fitness defects seen in wMelPop-infected A. aegypti could be explained by competition between the mosquito and the symbiont for essential blood meal nutrients, the profiles of which are suboptimal in non-human blood. Here, we examine cholesterol and amino acids as candidate molecules for competition, as they have critical roles in egg structural development and are known to vary between blood sources. We found that Wolbachia infection reduces total cholesterol levels in mosquitoes by 15-25 %. We then showed that cholesterol supplementation of a rat blood meal did not improve fecundity or egg viability deficits. Conversely, amino acid supplementation of sucrose before and after a sheep blood meal led to statistically significant increases in fecundity of approximately 15-20 eggs per female and egg viability of 30-40 %. This mosquito system provides the first empirical evidence of competition between Wolbachia and a host over amino acids and may suggest a general feature of Wolbachia-insect associations. These competitive processes could affect many aspects of host physiology and potentially mosquito fitness, a key concern for Wolbachia-based mosquito biocontrol

Number of suspected human cases (black triangles and black dashed line), reported animal bites (black dots and black solid line) and laboratory confirmed dog cases with 95% CI (gray dots and gray solid line), Bohol Province, 2000–2010.

<p>The shaded areas indicate the timing of round 1 (darker gray) and round 2 (lighter gray) mass dog vaccination.</p

Dog population, vaccination, rabies diagnosis, elimination and movement data, and human rabies and animal bite cases, Bohol, Philippines, 2000–2011

1<p>Source for dog population size estimation: Municipal Agriculture Office; Bureau of Agricultural Statisctics; House to house survey by barangay livestock aid (BALA).</p>2<p>Method of dog vaccination campaign: House to house only; *Mixture of central point and house to house.</p>3<p>After 2007, incidence was calculated using the more conservative dog population estimate e.g. for 2008, 100,752 dogs was used.</p>*<p>N.B. Omitted data means data is missing because it was not collected, and therefore is not necessarily zero.</p

Map of the province of Bohol Philippines.

<p>BOHOL FACTFILE. Total Population: 1,139,130. Total Households: 152,324. Total Land Area: 11,726 hectares. 47 municipalities, 1 city & 1,109 barangays or villages. 81 offshore islands & islets. 30 coastal municipalities and 304 coastal barangays. Annual per capita income: 16,478 PHP (378 US$). Annual per capita expenditure: 14,364 PHP (378 US$). Annual average family income: 77,291 PHP (1,770 US$). Annual average family expenditure: 66,907 PHP (1,534 US$). PHP = Philippine Pesos.</p