History of malaria treatment as a predictor of subsequent subclinical parasitaemia: A cross-sectional survey and malaria case records from three villages in Pailin, western Cambodia

Background: Treatment of the sub-clinical reservoir of malaria, which may maintain transmission, could be an important component of elimination strategies. The reliable detection of asymptomatic infections with low levels of parasitaemia requires high-volume quantitative polymerase chain reaction (uPCR), which is impractical to conduct on a large scale. It is unknown to what extent sub-clinical parasitaemias originate from recent or older clinical episodes. This study explored the association between clinical history of malaria and subsequent sub-clinical parasitaemia. Methods: In June 2013 a cross-sectional survey was conducted in three villages in Pailin, western Cambodia. Demographic and epidemiological data and blood samples were collected. Blood was tested for malaria by high-volume qP

Spread of artemisinin resistance in Plasmodium falciparum malaria.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and now poses a threat to the control and elimination of malaria. Mapping the geographic extent of resistance is essential for planning containment and elimination strategies. METHODS: Between May 2011 and April 2013, we enrolled 1241 adults and children with acute, uncomplicated falciparum malaria in an open-label trial at 15 sites in 10 countries (7 in Asia and 3 in Africa). Patients received artesunate, administered orally at a daily dose of either 2 mg per kilogram of body weight per day or 4 mg per kilogram, for 3 days, followed by a standard 3-day course of artemisinin-based combination therapy. Parasite counts in peripheral-blood samples were measured every 6 hours, and the parasite clearance half-lives were determined. RESULTS: The median parasite clearance half-lives ranged from 1.9 hours in the Democratic Republic of Congo to 7.0 hours at the Thailand-Cambodia border. Slowly clearing infections (parasite clearance half-life >5 hours), strongly associated with single point mutations in the "propeller" region of the P. falciparum kelch protein gene on chromosome 13 (kelch13), were detected throughout mainland Southeast Asia from southern Vietnam to central Myanmar. The incidence of pretreatment and post-treatment gametocytemia was higher among patients with slow parasite clearance, suggesting greater potential for transmission. In western Cambodia, where artemisinin-based combination therapies are failing, the 6-day course of antimalarial therapy was associated with a cure rate of 97.7% (95% confidence interval, 90.9 to 99.4) at 42 days. CONCLUSIONS: Artemisinin resistance to P. falciparum, which is now prevalent across mainland Southeast Asia, is associated with mutations in kelch13. Prolonged courses of artemisinin-based combination therapies are currently efficacious in areas where standard 3-day treatments are failing. (Funded by the U.K. Department of International Development and others; ClinicalTrials.gov number, NCT01350856.)

T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses

Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) are found in 168 PCR-confirmed SARS-CoV-2 infected volunteers, but are rare in 119 uninfected volunteers. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. By contrast, >90% of convalescent or unexposed people show proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. Memory responses to specific non-spike proteins provide a method to distinguish recent infection from pre-existing immunity in exposed populations

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Taking fair on the chin: The chemistry implementation network

The Chemistry Implementation Network (ChIN) is focused on supporting the FAIR Data needs of the research community regarding chemical related data. An Implementation Network is a consortium drawn from a community, in this case the chemistry discipline, committed to defining and constructing standards, materials and software in the spirit of the FAIR data principles and under the structure of the GO FAIR project. Furthermore, as a core science the ChIN has to reach beyond the chemistry community and support the use of chemical information in other disciplines. This will be facilitated through connections in the GO FAIR ecosystem of Implementation Networks. Examples of the FAIR chemical concepts that need to be supported include molecular and materials structures, chemical reactions, nomenclature and other chemical terminology and conventions. The ChIN aims to drive forward the application of the FAIR Data Principles relating to the full range of chemistry concepts that are key to the transparent and efficient communication of chemical information. Realizing the goal of FAIR chemistry data will require a culture change across the discipline. However this is best addressed once a critical mass of tools and approaches has been developed

Taking FAIR on the ChIN: The Chemistry Implementation Network

The Chemistry Implementation Network (ChIN) is focused on supporting the FAIR Data needs of the research community regarding chemical related data. Figure 1 shows the interoperation between the ChIN and key community-leading organizations.</span

Taking FAIR on the ChIN: The Chemistry Implementation Network

The Chemistry Implementation Network (ChIN) is focused on supporting the FAIR Data needs of the research community regarding chemical related data. Figure 1 shows the interoperation between the ChIN and key community-leading organizations.</span

A multi-level spatial analysis of clinical malaria and subclinical Plasmodium infections in Pailin Province, Cambodia.

BackgroundThe malaria burden is decreasing throughout the Greater Mekong Subregion, however transmission persists in some areas. Human movement, subclinical infections and complicated transmission patterns contribute to the persistence of malaria. This research describes the micro-geographical epidemiology of both clinical malaria and subclinical Plasmodium infections in three villages in Western Cambodia.MethodsThree villages in Western Cambodia were selected for the study based on high reported Plasmodium falciparum incidence. A census was conducted at the beginning of the study, including demographic information and travel history. The total population was 1766. Cross-sectional surveys were conducted every three months from June 2013 to June 2014. Plasmodium infections were detected using an ultra-sensitive, high-volume, quantitative polymerase chain reaction (uPCR) technique. Clinical episodes were recorded by village health workers. The geographic coordinates (latitude and longitude) were collected for all houses and all participants were linked to their respective houses using a demographic surveillance system. Written informed consent was obtained from all participants.ResultsMost clinical episodes and subclinical infections occurred within a single study village. Clinical Plasmodium vivax episodes clustered spatially in each village but only lasted for a month. In one study village subclinical infections clustered in geographic proximity to clusters of clinical episodes. The largest risk factor for clinical P. falciparum episodes was living in a house where another clinical P. falciparum episode occurred (model adjusted odds ratio (AOR): 6.9; CI: 2.3-19. 8). Subclinical infections of both P. vivax and P. falciparum were associated with clinical episodes of the same species (AOR: 5.8; CI: 1.5-19.7 for P. falciparum and AOR: 14.6; CI: 8.6-25.2 for P. vivax) and self-reported overnight visits to forested areas (AOR = 3.8; CI: 1.8-7. 7 for P. falciparum and AOR = 2.9; CI: 1.7-4.8 for P. vivax).DiscussionSpatial clustering within the villages was transient, making the prediction of spatial clusters difficult. Interventions that are dependent on predicting spatial clusters (such as reactive case detection) would only have detected a small proportion of cases unless the entire village was screened within a limited time frame and with a highly sensitive diagnostic test. Subclinical infections may be acquired outside of the village (particularly in forested areas) and may play an important role in transmission