Mass drug administration (MDA) with antimalarials has been shown to reduce prevalence and interrupt transmission in small populations, in populations with reliable access to antimalarial drugs, and in populations where sustained improvements in diagnosis and treatment are possible. In addition, when MDA is effective it eliminates both drug-resistant parasites and drug-sensitive parasites, which has the long-term benefit of extending the useful therapeutic life of first-line therapies for all populations, not just the focal population where MDA was carried out. However, in order to plan elimination measures effectively, it is necessary to characterize the conditions under which failed MDA could exacerbate resistance. We use an individual-based stochastic model of Plasmodium falciparum transmission to evaluate this risk for MDA using dihydroartemisinin-piperaquine (DHA-PPQ), in populations where access to antimalarial treatments may not be uniformly high and where re-importation of drug-resistant parasites may be common. We find that artemisinin-resistance evolution at the kelch13 locus can be accelerated by MDA when all three of the following conditions are met: (1) strong genetic bottlenecking that falls short of elimination, (2) re-importation of artemisinin-resistant genotypes, and (3) continued selection pressure during routine case management post-MDA. Accelerated resistance levels are not immediate but follow the rebound of malaria cases post-MDA, if this is allowed to occur. Crucially, resistance is driven by the selection pressure during routine case management post-MDA and not the selection pressure exerted during the MDA itself. Second, we find that increasing treatment coverage post-MDA increases the probability of local elimination in low-transmission regions (prevalence < 2%) in scenarios with both low and high levels of drug-resistance importation. This emphasizes the importance of planning for and supporting high coverage of diagnosis and treatment post-MDA.

Swine pathogens have a long history of zoonotic transmission to humans, occasionally leading to sustained outbreaks or pandemics. Through a retrospective epidemiological study of swine populations in China, we describe novel lineages of porcine hemagglutinating encephalomyelitis virus (PHEV) complex coronaviruses (CoVs) that cause exclusively respiratory symptoms with no signs of the neurological symptoms typically associated with classical PHEV infection. Through large-scale epidemiological surveillance, we show that these novel lineages have circulated in at least eight provinces in southeastern China. Phylogenetic and recombination analyses of twenty-four genomes identified two major viral lineages causing respiratory symptoms with extensive recombination within them, between them, and between classical PHEV and the novel respiratory variant PHEV (rvPHEV) lineages. Divergence times among the sampled lineages in the PHEV virus complex date back to 1886-1958 (mean estimate 1928), with the two major rvPHEV lineages separating approximately 20 years later. Many rvPHEV viruses show amino acid substitutions at the carbohydrate-binding site of hemagglutinin esterase (HE) and/or have lost the cysteine required for HE dimerization. This resembles the early adaptation of human CoVs, where HE lost its hemagglutination ability to adapt to growth in the human respiratory tract. Our study represents the first report of the evolutionary history of rvPHEV circulating in swine and highlights the importance of characterizing CoV diversity and recombination in swine to identify pathogens with outbreak potential that could threaten swine farming.

Owing to the finding that Dengvaxia^® (the only licensed dengue vaccine to date) increases the risk of severe illness among seronegative recipients, the World Health Organization has recommended screening individuals for their serostatus prior to vaccination. To decide whether and how to carry out screening, it is necessary to estimate the transmission intensity of dengue and to understand the performance of the screening method. In this study, we inferred the annual force of infection (FOI; a measurement of transmission intensity) of dengue virus in three locations in Vietnam: An Giang (FOI = 0.04 for the below 10 years age group and FOI = 0.20 for the above 10 years age group), Ho Chi Minh City (FOI = 0.12) and Quang Ngai (FOI = 0.05). In addition, we show that using a quantitative approach to immunoglobulin G (IgG) levels (measured by indirect enzyme-linked immunosorbent assays) can help to distinguish individuals with primary exposures (primary seropositive) from those with secondary exposures (secondary seropositive). We found that primary-seropositive individuals-the main targets of the vaccine-tend to have a lower IgG level, and, thus, they have a higher chance of being misclassified as seronegative than secondary-seropositive cases. However, screening performance can be improved by incorporating patient age and transmission intensity into the interpretation of IgG levels.

BACKGROUND:The number of Plasmodium falciparum malaria cases around the world has decreased substantially over the last 15 years, but with the spread of resistance against anti-malarial drugs and insecticides, this decline may not continue. There is an urgent need to consider alternative, accelerated strategies to eliminate malaria in countries like Lao PDR, where there are a few remaining endemic areas. A deterministic compartmental modelling tool was used to develop an integrated strategy for P. falciparum elimination in the Savannakhet province of Lao PDR. The model was designed to include key aspects of malaria transmission and integrated control measures, along with a user-friendly interface. RESULTS:Universal coverage was the foundation of the integrated strategy, which took the form of the deployment of community health workers who provided universal access to early diagnosis, treatment and long-lasting insecticidal nets. Acceleration was included as the deployment of three monthly rounds of mass drug administration targeted towards high prevalence villages, with the addition of three monthly doses of the RTS,S vaccine delivered en masse to the same high prevalence sub-population. A booster dose of vaccine was added 1 year later. The surveillance-as-intervention component of the package involved the screening and treatment of individuals entering the simulated population. CONCLUSIONS:In this modelling approach, the sequential introduction of a series of five available interventions in an integrated strategy was predicted to be sufficient to stop malaria transmission within a 3-year period. These interventions comprised universal access to early diagnosis and adequate treatment, improved access to long-lasting insecticidal nets, three monthly rounds of mass drug administration together with RTS,S vaccination followed by a booster dose of vaccine, and screening and treatment of imported cases.

Since the first reports of a novel severe acute respiratory syndrome (SARS)-like coronavirus in December 2019 in Wuhan, China, there has been intense interest in understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the human population. Recent debate has coalesced around two competing ideas: a "laboratory escape" scenario and zoonotic emergence. Here, we critically review the current scientific evidence that may help clarify the origin of SARS-CoV-2.