Clinical outcomes for young people with screening-detected and clinically-diagnosed rheumatic heart disease in Fiji.

Echocardiographic screening is under consideration as a disease control strategy for rheumatic heart disease (RHD). However, clinical outcomes of young people with screening-detected RHD are unknown. We aimed to describe the outcomes for a cohort with screening-detected RHD, in comparison to patients with clinically-diagnosed RHD. A retrospective cohort study included all young people with screening-detected RHD in the Central Division of Fiji in the primary cohort. Screen-negative and clinically-diagnosed comparison groups were matched 1:1 to the primary cohort. Data were collected on mortality, clinical complications and healthcare utilisation from the electronic and paper health records and existing databases. Seventy participants were included in each group. Demographic characteristics of the groups were similar (median age 11years, 69% female, median follow-up 7years). There were nine (12.9%) RHD-related deaths in the clinically-diagnosed group and one (1.4%) in the screening-detected group (Incident Rate Ratio: 9.6, 95% CI 1.3-420.6). Complications of RHD were observed in 39 (55.7%) clinically-diagnosed cases, four (20%) screening-detected cases and one (1.4%) screen-negative case. There were significant differences in the cumulative complication curves of the groups (p<0.001). Rates of admission and surgery were highest in the clinically-diagnosed group, and higher in the screening-detected than screen-negative group. Young people with screening-detected RHD have worse health outcomes than screen-negative cases in Fiji. The prognosis of clinically-diagnosed RHD remains poor, with very high mortality and complication rates. Further studies in other settings will inform RHD screening policy. Comprehensive control strategies are required for disease prevention

Standardization of epidemiological surveillance of acute rheumatic fever

Acute rheumatic fever (ARF) is a multiorgan inflammatory disorder that results from the body’s autoimmune response to pharyngitis or a skin infection caused by Streptococcus pyogenes (Strep A). Acute rheumatic fever mainly affects those in low- and middle-income nations, as well as in indigenous populations in wealthy nations, where initial Strep A infections may go undetected. A single episode of ARF puts a person at increased risk of developing long-term cardiac damage known as rheumatic heart disease. We present case definitions for both definite and possible ARF, including initial and recurrent episodes, according to the 2015 Jones Criteria, and we discuss current tests available to aid in the diagnosis. We outline the considerations specific to ARF surveillance methodology, including discussion on where and how to conduct active or passive surveillance (eg, early childhood centers/schools, households, primary healthcare, administrative database review), participant eligibility, and the surveillance population. Additional considerations for ARF surveillance, including implications for secondary prophylaxis and follow-up, ARF registers, community engagement, and the impact of surveillance, are addressed. Finally, the core elements of case report forms for ARF, monitoring and audit requirements, quality control and assurance, and the ethics of conducting surveillance are discussed

The cost-of-illness due to rheumatic heart disease: national estimates for Fiji

Background Rheumatic heart disease (RHD) is a chronic valvular heart disease that is responsible for a heavy burden of premature mortality in low- and middle-income countries. The total costs of RHD are important to health policy and research investment decisions. We estimate for the first time the total cost of RHD for Fiji (2008–2012) using a cost-of-illness approach and novel primary data on RHD disease burden and costs. Methods RHD cases were identified using probabilistic record linkage across four routine data sources: (1) the Fiji RHD Control Program, (2) national hospital admissions records, (3) the Ministry of Health database of cause-specific deaths and (4) hospital ECG clinic registers. For each individual with RHD, we obtained information on RHD hospital admissions, treatment and death. We conducted a prevalence-based cost-of-illness analysis, including bottom-up assessment of indirect and direct (healthcare) costs. Results The estimated cost of RHD in Fiji for 2008–2012 was year-2010 $FJ91.6 million (approximately US$47.7 million). Productivity losses from premature mortality constituted the majority of costs (71.4%). Indirect costs were 27-fold larger than the direct costs. Conclusions RHD leads to a heavy economic burden in Fiji. Improved prevention strategies for RHD will likely confer substantial economic benefits to the country

Translational web robots for pathogen genome analysis

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Quantum phase transition in a single-molecule quantum dot

Quantum criticality is the intriguing possibility offered by the laws of quantum mechanics when the wave function of a many-particle physical system is forced to evolve continuously between two distinct, competing ground states. This phenomenon, often related to a zero-temperature magnetic phase transition, can be observed in several strongly correlated materials such as heavy fermion compounds or possibly high-temperature superconductors, and is believed to govern many of their fascinating, yet still unexplained properties. In contrast to these bulk materials with very complex electronic structure, artificial nanoscale devices could offer a new and simpler vista to the comprehension of quantum phase transitions. This long-sought possibility is demonstrated by our work in a fullerene molecular junction, where gate voltage induces a crossing of singlet and triplet spin states at zero magnetic field. Electronic tunneling from metallic contacts into the $\rm{C_{60}}$ quantum dot provides here the necessary many-body correlations to observe a true quantum critical behavior.Comment: 8 pages, 5 figure

Standardization of epidemiological surveillance of rheumatic heart disease

Rheumatic heart disease (RHD) is a long-term sequela of acute rheumatic fever (ARF), which classically begins after an untreated or undertreated infection caused by Streptococcus pyogenes (Strep A). RHD develops after the heart valves are permanently damaged due to ARF. RHD remains a leading cause of morbidity and mortality in young adults in resource-limited and low- and middle-income countries. This article presents case definitions for latent, suspected, and clinical RHD for persons with and without a history of ARF, and details case classifications, including differentiating between definite or borderline according to the 2012 World Heart Federation echocardiographic diagnostic criteria. This article also covers considerations specific to RHD surveillance methodology, including discussions on echocardiographic screening, where and how to conduct active or passive surveillance (eg, early childhood centers/schools, households, primary healthcare), participant eligibility, and the surveillance population. Additional considerations for RHD surveillance, including implications for secondary prophylaxis and follow-up, RHD registers, community engagement, and the negative impact of surveillance, are addressed. Finally, the core elements of case report forms for RHD, monitoring and audit requirements, quality control and assurance, and the ethics of conducting surveillance are discussed

Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an <i>in vitro</i> model of CNS tuberculosis

Central nervous system tuberculosis (CNS TB) has a high mortality and morbidity associated with severe inflammation. The blood-brain barrier (BBB) protects the brain from inflammation but the mechanisms causing BBB damage in CNS TB are uncharacterized. We demonstrate that Mycobacterium tuberculosis (Mtb) causes breakdown of type IV collagen and decreases tight junction protein (TJP) expression in a co-culture model of the BBB. This increases permeability, surface expression of endothelial adhesion molecules and leukocyte transmigration. TJP breakdown was driven by Mtb-dependent secretion of matrix metalloproteinase (MMP)-9. TJP expression is regulated by Sonic hedgehog (Shh) through transcription factor Gli-1. In our model, the hedgehog pathway was downregulated by Mtb-stimulation, but Shh levels in astrocytes were unchanged. However, Scube2, a glycoprotein regulating astrocyte Shh release was decreased, inhibiting Shh delivery to brain endothelial cells. Activation of the hedgehog pathway by addition of a Smoothened agonist or by addition of exogenous Shh, or neutralizing MMP-9 activity, decreased permeability and increased TJP expression in the Mtb-stimulated BBB co-cultures. In summary, the BBB is disrupted by downregulation of the Shh pathway and breakdown of TJPs, secondary to increased MMP-9 activity which suggests that these pathways are potential novel targets for host directed therapy in CNS TB

Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences

Profiling phylogenetic marker genes, such as the 16S rRNA gene, is a key tool for studies of microbial communities but does not provide direct evidence of a community’s functional capabilities. Here we describe PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a computational approach to predict the functional composition of a metagenome using marker gene data and a database of reference genomes. PICRUSt uses an extended ancestral-state reconstruction algorithm to predict which gene families are present and then combines gene families to estimate the composite metagenome. Using 16S information, PICRUSt recaptures key findings from the Human Microbiome Project and accurately predicts the abundance of gene families in host-associated and environmental communities, with quantifiable uncertainty. Our results demonstrate that phylogeny and function are sufficiently linked that this ‘predictive metagenomic’ approach should provide useful insights into the thousands of uncultivated microbial communities for which only marker gene surveys are currently available

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods