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975 result(s) for "Moore, Sean"
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The current burden of Japanese encephalitis and the estimated impacts of vaccination: Combining estimates of the spatial distribution and transmission intensity of a zoonotic pathogen
Japanese encephalitis virus (JEV) is a major cause of neurological disability in Asia and causes thousands of severe encephalitis cases and deaths each year. Although Japanese encephalitis (JE) is a WHO reportable disease, cases and deaths are significantly underreported and the true burden of the disease is not well understood in most endemic countries. Here, we first conducted a spatial analysis of the risk factors associated with JE to identify the areas suitable for sustained JEV transmission and the size of the population living in at-risk areas. We then estimated the force of infection (FOI) for JE-endemic countries from age-specific incidence data. Estimates of the susceptible population size and the current FOI were then used to estimate the JE burden from 2010 to 2019, as well as the impact of vaccination. Overall, 1,543.1 million (range: 1,292.6-2,019.9 million) people were estimated to live in areas suitable for endemic JEV transmission, which represents only 37.7% (range: 31.6-53.5%) of the over four billion people living in countries with endemic JEV transmission. Based on the baseline number of people at risk of infection, there were an estimated 56,847 (95% CI: 18,003-184,525) JE cases and 20,642 (95% CI: 2,252-77,204) deaths in 2019. Estimated incidence declined from 81,258 (95% CI: 25,437-273,640) cases and 29,520 (95% CI: 3,334-112,498) deaths in 2010, largely due to increases in vaccination coverage which have prevented an estimated 314,793 (95% CI: 94,566-1,049,645) cases and 114,946 (95% CI: 11,421-431,224) deaths over the past decade. India had the largest estimated JE burden in 2019, followed by Bangladesh and China. From 2010-2019, we estimate that vaccination had the largest absolute impact in China, with 204,734 (95% CI: 74,419-664,871) cases and 74,893 (95% CI: 8,989-286,239) deaths prevented, while Taiwan (91.2%) and Malaysia (80.1%) had the largest percent reductions in JE burden due to vaccination. Our estimates of the size of at-risk populations and current JE incidence highlight countries where increasing vaccination coverage could have the largest impact on reducing their JE burden.
Biological Control of a Phytosanitary Pest (Thaumatotibia leucotreta): A Case Study
Thaumatotibia leucotreta, known as the false codling moth, is a pest of citrus and other crops in sub-Saharan Africa. As it is endemic to this region and as South Africa exports most of its citrus around the world, T. leucotreta has phytosanitary status for most markets. This means that there is zero tolerance for any infestation with live larvae in the market. Consequently, control measures prior to exporting must be exemplary. Certain markets require a standalone postharvest disinfestation treatment for T. leucotreta. However, the European Union accepts a systems approach, consisting of three measures and numerous components within these measures. Although effective preharvest control measures are important under all circumstances, they are most critical where a standalone postharvest disinfestation treatment is not applied, such as within a systems approach. Conventional wisdom may lead a belief that effective chemical control tools are imperative to achieve this end. However, we demonstrate that it is possible to effectively control T. leucotreta to a level acceptable for a phytosanitary market, using only biological control tools. This includes parasitoids, predators, microbial control, semiochemicals, and sterile insects. Simultaneously, on-farm and environmental safety is improved and compliance with the increasing stringency of chemical residue requirements imposed by markets is achieved.
Mapping the burden of cholera in sub-Saharan Africa and implications for control: an analysis of data across geographical scales
Cholera remains a persistent health problem in sub-Saharan Africa and worldwide. Cholera can be controlled through appropriate water and sanitation, or by oral cholera vaccination, which provides transient (∼3 years) protection, although vaccine supplies remain scarce. We aimed to map cholera burden in sub-Saharan Africa and assess how geographical targeting could lead to more efficient interventions. We combined information on cholera incidence in sub-Saharan Africa (excluding Djibouti and Eritrea) from 2010 to 2016 from datasets from WHO, Médecins Sans Frontières, ProMED, ReliefWeb, ministries of health, and the scientific literature. We divided the study region into 20 km × 20 km grid cells and modelled annual cholera incidence in each grid cell assuming a Poisson process adjusted for covariates and spatially correlated random effects. We combined these findings with data on population distribution to estimate the number of people living in areas of high cholera incidence (>1 case per 1000 people per year). We further estimated the reduction in cholera incidence that could be achieved by targeting cholera prevention and control interventions at areas of high cholera incidence. We included 279 datasets covering 2283 locations in our analyses. In sub-Saharan Africa (excluding Djibouti and Eritrea), a mean of 141 918 cholera cases (95% credible interval [CrI] 141 538–146 505) were reported per year. 4·0% (95% CrI 1·7–16·8) of districts, home to 87·2 million people (95% CrI 60·3 million to 118·9 million), have high cholera incidence. By focusing on the highest incidence districts first, effective targeted interventions could eliminate 50% of the region's cholera by covering 35·3 million people (95% CrI 26·3 million to 62·0 million), which is less than 4% of the total population. Although cholera occurs throughout sub-Saharan Africa, its highest incidence is concentrated in a small proportion of the continent. Prioritising high-risk areas could substantially increase the efficiency of cholera control programmes. The Bill & Melinda Gates Foundation.
Thermal-bias PCR: generation of amplicon libraries without degenerate primer interference
The polymerase chain reaction (PCR) has been used to amplify specific gene regions for many taxonomic studies and there have been substantial efforts to develop protocols that efficiently amplify target regions from a majority of mixed-template populations. Most protocols include the use of degenerate oligonucleotide primer pools, which contain mixed nucleotide sequences to improve priming from templates containing non-consensus sequence variations in their primer-binding sites. In this work, computational modeling and experimental measurements revealed that degenerate primers reduce efficiency well before a substantial product pool has been generated. It was also discovered that non-degenerate primers produced amplicons significantly better than their degenerate counterparts when amplifying either a consensus or a non-consensus target. Using quantitative, real-time PCR (qPCR) and data fitting as a guide, a new PCR protocol was developed that avoids the use of degenerate primers and allows for the stable amplification of targets containing mismatches to the targeting primers. This protocol involves the use of only two non-degenerate primers with no intermediate processing steps and it allows for the reproducible production of amplicon sequencing libraries that maintain the fractional representations of rare members.
Estimating unobserved SARS-CoV-2 infections in the United States
By March 2020, COVID-19 led to thousands of deaths and disrupted economic activity worldwide. As a result of narrow case definitions and limited capacity for testing, the number of unobserved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during its initial invasion of the United States remains unknown. We developed an approach for estimating the number of unobserved infections based on data that are commonly available shortly after the emergence of a new infectious disease. The logic of our approach is, in essence, that there are bounds on the amount of exponential growth of new infections that can occur during the first few weeks after imported cases start appearing. Applying that logic to data on imported cases and local deaths in the United States through 12 March, we estimated that 108,689 (95% posterior predictive interval [95%PPI]: 1,023 to 14,182,310) infections occurred in the United States by this date. By comparing the model’s predictions of symptomatic infections with local cases reported over time, we obtained daily estimates of the proportion of symptomatic infections detected by surveillance. This revealed that detection of symptomatic infections decreased throughout February as exponential growth of infections outpaced increases in testing. Between 24 February and 12 March, we estimated an increase in detection of symptomatic infections, which was strongly correlated (median: 0.98; 95% PPI: 0.66 to 0.98) with increases in testing. These results suggest that testing was a major limiting factor in assessing the extent of SARS-CoV-2 transmission during its initial invasion of the United States.
Microbial cues stimulate linear growth in undernourished mice
A new study has found that a strain of the gut bacterium Lactiplantibacillus plantarum activates a NOD2–type I interferon–insulin-like growth factor 1 pathway in young mice to partially protect against the deleterious growth effects of a diet deficient in protein and fat. Could live biotherapeutic products or their derivatives unlock the full potential of nutritional interventions against childhood stunting?
Standard RUTF vs. locally-made RUSF for acutely malnourished children: A quasi-experimental comparison of the impact on growth and compliance in a rural community of Pakistan
The reduction in severe and moderate acute malnutrition (SAM and MAM) rates in Pakistan has been sub-optimal compared to other low-and middle-income countries (LMICs). Specially-formulated products have been designed globally to manage SAM and MAM, such as ready-to-use therapeutic food (RUTF) and ready-to-use supplementary food (RUSF), with variable efficacies. RUTF is primarily produced and patented in industrialized countries, raising supply challenges in resource-constrained regions with a high burden of acute malnutrition. RUSF minimizes costs by using locally-available ingredients while providing similar nutritional value. In this study, we compared the efficacy, side effects, and compliance of two months of supplementation with either RUTF or RUSF. Children aged nine months in the rural district of Matiari, Pakistan, with a weight-for-height z-score (WHZ) <-2 received either RUTF (500 kcal sachet) for two months in 2015 or RUSF (520 kcal sachet) for two months in 2018. The RUSF group had a higher height gain and mid-upper arm circumferences (MUAC) score. Higher compliance was noted with lower side effects in the RUSF group. A higher compliance rate did correlate with the growth parameters in respective groups. Our study found that both RUTF and RUSF partially improve the anthropometric status of acutely malnourished children, with neither being superior to the other.
The Enteric Nervous System and Its Emerging Role as a Therapeutic Target
The gastrointestinal (GI) tract is innervated by the enteric nervous system (ENS), an extensive neuronal network that traverses along its walls. Due to local reflex circuits, the ENS is capable of functioning with and without input from the central nervous system. The functions of the ENS range from the propulsion of food to nutrient handling, blood flow regulation, and immunological defense. Records of it first being studied emerged in the early 19th century when the submucosal and myenteric plexuses were discovered. This was followed by extensive research and further delineation of its development, anatomy, and function during the next two centuries. The morbidity and mortality associated with the underdevelopment, infection, or inflammation of the ENS highlight its importance and the need for us to completely understand its normal function. This review will provide a general overview of the ENS to date and connect specific GI diseases including short bowel syndrome with neuronal pathophysiology and current therapies. Exciting opportunities in which the ENS could be used as a therapeutic target for common GI diseases will also be highlighted, as the further unlocking of such mechanisms could open the door to more therapy-related advances and ultimately change our treatment approach.
Estimation of Lassa fever incidence rates in West Africa: Development of a modeling framework to inform vaccine trial design
Lassa fever (LF) is an acute viral hemorrhagic disease endemic to West Africa that has been declared a priority disease by the World Health Organization due to its severity and the lack of a vaccine or effective treatment options. Several candidate vaccines are currently in development and are expected to be ready for phase III field efficacy trials soon. However, most LF cases and deaths are believed to go unreported, and as a result we lack a clear understanding of several aspects of LF epidemiology and immunology that are critical to the design of vaccine efficacy trials. To help guide vaccine trial design and trial site selection we estimated the force of infection (FOI) from rodent hosts to humans in all 1st and 2nd administrative units in West Africa from published seroprevalence studies. We next estimated LF reporting probabilities using these FOI estimates and LF case and death reports and then projected FOI in all admin1 and admin2 areas without seroprevalence data. We then extrapolated age-specific LF incidence rates from FOI estimates under different assumptions regarding the level of protection against reinfection among seropositive and seronegative individuals with a history of prior infection. Projected FOI estimates and modeled annual LF incidence rates indicate that Sierra Leone, southern Guinea, and a few areas within Nigeria would likely experience the highest LF case incidence rates for a vaccine trial. Estimated LF incidence rates were highly sensitive to assumptions about Lassa immunology, particularly the frequency of seroreversion among previously infected individuals and the extent to which seroreverted individuals retain protection against reinfection and more severe disease outcomes. Our spatial LF incidence rate estimates, along with the interannual and seasonal variability in these estimates and estimates of baseline seroprevalence, could be used for vaccine trial site selection, choosing the target population (e.g., age and serostatus), and maximizing a trial's statistical power.