Prediction of Dengue Disease Severity among Pediatric Thai Patients Using Early Clinical Laboratory Indicators

Background

Dengue virus is endemic in tropical and sub-tropical resource-poor countries. Dengue illness can range from a nonspecific febrile illness to a severe disease, Dengue Shock Syndrome (DSS), in which patients develop circulatory failure. Earlier diagnosis of severe dengue illnesses would have a substantial impact on the allocation of health resources in endemic countries.

Methods and Findings

We compared clinical laboratory findings collected within 72 hours of fever onset from a prospective cohort children presenting to one of two hospitals (one urban and one rural) in Thailand. Classification and regression tree analysis was used to develop diagnostic algorithms using different categories of dengue disease severity to distinguish between patients at elevated risk of developing a severe dengue illness and those at low risk. A diagnostic algorithm using WBC count, percent monocytes, platelet count, and hematocrit achieved 97% sensitivity to identify patients who went on to develop DSS while correctly excluding 48% of non-severe cases. Addition of an indicator of severe plasma leakage to the WHO definition led to 99% sensitivity using WBC count, percent neutrophils, AST, platelet count, and age.

Conclusions

This study identified two easily applicable diagnostic algorithms using early clinical indicators obtained within the first 72 hours of illness onset. The algorithms have high sensitivity to distinguish patients at elevated risk of developing severe dengue illness from patients at low risk, which included patients with mild dengue and other non-dengue febrile illnesses. Although these algorithms need to be validated in other populations, this study highlights the potential usefulness of specific clinical indicators early in illness.     

Diversity and phylogenetic relationships of <Emphasis Type="Italic">Glossina</Emphasis> populations in Nigeria and the Cameroonian border region

Background

Tsetse flies are vectors of trypanosomes, parasites that cause devastating disease in humans and livestock. In the course of vector control programmes it is necessary to know about the Glossina species present in the study area, the population dynamics and the genetic exchange between tsetse fly populations.

Results

To achieve an overview of the tsetse fly diversity in Nigeria and at the Nigeria-Cameroon border, tsetse flies were trapped and collected between February and March 2014 and December 2016. Species diversity was determined morphologically and by analysis of Cytochrome C Oxidase SU1 (COI) gene sequences. Internal transcribed spacer-1 (ITS-1) sequences were compared to analyse variations within populations. The most dominant species were G. m. submorsitans, G. tachinoides and G. p. palpalis. In Yankari Game Reserve and Kainji Lake National Park, G. submorsitans and G. tachinoides were most frequent, whereas in Old Oyo National Park and Ijah Gwari G. p. palpalis was the dominant species. Interestingly, four unidentified species were recorded during the survey, for which no information on COI or ITS-1 sequences exists. G. p. palpalis populations showed a segregation in two clusters along the Cameroon-Nigerian border.

Conclusions

The improved understanding of the tsetse populations in Nigeria will support decisions on the scale in which vector control is likely to be more effective. In order to understand in more detail how isolated these populations are, it is recommended that further studies on gene flow be carried out using other markers, including microsatellites.

     

Large old trees increase growth under shifting climatic constraints: Aligning tree longevity and individual growth dynamics in primary mountain spruce forests

In a world of accelerating changes in environmental conditions driving tree growth, tradeoffs between tree growth rate and longevity could curtail the abundance of large old trees (LOTs), with potentially dire consequences for biodiversity and carbon storage. However, the influence of tree-level tradeoffs on forest structure at landscape scales will also depend on disturbances, which shape tree size and age distribution, and on whether LOTs can benefit from improved growing conditions due to climate warming. We analyzed temporal and spatial variation in radial growth patterns from ~5000 Norway spruce (Picea abies [L.] H. Karst) live and dead trees from the Western Carpathian primary spruce forest stands. We applied mixed-linear modeling to quantify the importance of LOT growth histories and stand dynamics (i.e., competition and disturbance factors) on lifespan. Finally, we assessed regional synchronization in radial growth variability over the 20th century, and modeled the effects of stand dynamics and climate on LOTs recent growth trends. Tree age varied considerably among forest stands, implying an important role of disturbance as an age constraint. Slow juvenile growth and longer period of suppressed growth prolonged tree lifespan, while increasing disturbance severity and shorter time since last disturbance decreased it. The highest age was not achieved only by trees with continuous slow growth, but those with slow juvenile growth followed by subsequent growth releases. Growth trend analysis demonstrated an increase in absolute growth rates in response to climate warming, with late summer temperatures driving the recent growth trend. Contrary to our expectation that LOTs would eventually exhibit declining growth rates, the oldest LOTs (>400 years) continuously increase growth throughout their lives, indicating a high phenotypic plasticity of LOTs for increasing biomass, and a strong carbon sink role of primary spruce forests under rising temperatures, intensifying droughts, and increasing bark beetle outbreaks.     

Osteogenesis imperfecta due to recurrent point mutations at CpG dinucleotides in the COL1A1 gene of type I collagen

Summary Most individuals with osteogenesis imperfecta (OI) are heterozygous for dominant mutations in one of the genes that encode the chains of type I collagen. Each of the more than 30 mutations characterized to date has been unique to the affected member (s) of the family. We have determined that two individuals with a progressive deforming variety of OI, OI type III, have the same new dominant mutation [1(I)gly154 to arg] and that two unrelated infants with perinatal lethal OI, OI type II, share a second new dominant muation [1(I)gly1003 to ser]. These mutations occurred at CpG dinucleotides, in a manner consistent with deamination of a methylated cytosine residue, and raise the possibility that CpG dinucleotides are common sites of recurrent mutations in collagen genes. Further, these findings confirm that the OI type-III phenotype, previously thought to be inherited in an autosomal recessive manner, can result from new dominant mutations in the COL1A1 gene of type-I collagen.     

Comparison of the hemolysis machinery in two evolutionarily distant blood-feeding arthropod vectors of human diseases

Host blood protein digestion plays a pivotal role in the ontogeny and reproduction of hematophagous vectors. The gut of hematophagous arthropods stores and slowly digests host blood and represents the primary gateway for transmitted pathogens. The initial step in blood degradation is induced lysis of host red blood cells (hemolysis), which releases hemoglobin for subsequent processing by digestive proteolytic enzymes. The activity cycles and characteristics of hemolysis in vectors are poorly understood. Hence, we investigated hemolysis in two evolutionarily distant blood-feeding arthropods: The mosquito Culex pipiens and the soft tick Argas persicus, both of which are important human and veterinary disease vectors. Hemolysis in both species was cyclical after blood meal ingestion. Maximum digestion occurs under slightly alkaline conditions in females. Hemolytic activity appears to be of lipoid origin in C. pipiens and enzymatic activity (proteolytic) in A. persicus. We have assessed the effect of pH, incubation time, and temperature on hemolytic activity and the hemolysin. The susceptibility of red blood cells from different hosts to the hemolysin and the effect of metabolic inhibition of hemolytic activity were assessed. We conclude that in C. pipiens and A. persicus midgut hemolysins control the amplitude of blood lysis step to guarantee an efficient blood digestion.     

Hormone‐mediated foraging strategies in an uncertain environment: Insights into the at‐sea behavior of a marine predator

1. Hormones are extensively known to be physiological mediators of energy mobilization and allow animals to adjust behavioral performance in response to their environment, especially within a foraging context.
2. Few studies, however, have narrowed focus toward the consistency of hormonal patterns and their impact on individual foraging behavior. Describing these relationships can further our understanding of how individuals cope with heterogeneous environments and exploit different ecological niches.
3. To address this, we measured between‐ and within‐individual variation of basal cortisol (CORT), thyroid hormone T3, and testosterone (TEST) levels in wild adult female Galápagos sea lions (Zalophus wollebaeki) and analyzed how these hormones may be associated with foraging strategies. In this marine predator, females exhibit one of three spatially and temporally distinct foraging patterns (i.e., “benthic,” “pelagic,” and “night” divers) within diverse habitat types.
4. Night divers differentiated from other strategies by having lower T3 levels. Considering metabolic costs, night divers may represent an energetically conservative strategy with shorter dive durations, depths, and descent rates to exploit prey which migrate up the water column based on vertical diel patterns.
5. Intriguingly, CORT and TEST levels were highest in benthic divers, a strategy characterized by congregating around limited, shallow seafloors to specialize on confined yet reliable prey. This pattern may reflect hormone‐mediated behavioral responses to specific risks in these habitats, such as high competition with conspecifics, prey predictability, or greater risks of predation.
6. Overall, our study highlights the collective effects of hormonal and ecological variation on marine foraging. In doing so, we provide insights into how mechanistic constraints and environmental pressures may facilitate individual specialization in adaptive behavior in wild populations.

     

Social environment and genetics underlie body site‐specific microbiomes of Yellowstone National Park gray wolves (Canis lupus)

The host‐associated microbiome is an important player in the ecology and evolution of species. Despite growing interest in the medical, veterinary, and conservation communities, there remain numerous questions about the primary factors underlying microbiota, particularly in wildlife. We bridged this knowledge gap by leveraging microbial, genetic, and observational data collected in a wild, pedigreed population of gray wolves (Canis lupus) inhabiting Yellowstone National Park. We characterized body site‐specific microbes across six haired and mucosal body sites (and two fecal samples) using 16S rRNA amplicon sequencing. At the phylum level, we found that the microbiome of gray wolves primarily consists of Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, and Proteobacteria, consistent with previous studies within Mammalia and Canidae. At the genus level, we documented body site‐specific microbiota with functions relevant to microenvironment and local physiological processes. We additionally employed observational and RAD sequencing data to examine genetic, demographic, and environmental correlates of skin and gut microbiota. We surveyed individuals across several levels of pedigree relationships, generations, and social groups, and found that social environment (i.e., pack) and genetic relatedness were two primary factors associated with microbial community composition to differing degrees between body sites. We additionally reported body condition and coat color as secondary factors underlying gut and skin microbiomes, respectively. We concluded that gray wolf microbiota resemble similar host species, differ between body sites, and are shaped by numerous endogenous and exogenous factors. These results provide baseline information for this long‐term study population and yield important insights into the evolutionary history, ecology, and conservation of wild wolves and their associated microbes.     

The int genes of bacteriophages P22 and λ are regulated by different mechanisms

Bacteriophage P22 and λ are related bacteriophages with similar gene organizations. In λ the cII-dependent P_I promoter is responsible for λint gene expression. The only apparent counterpart to P_I in P22 is oriented in the opposite direction, and cannot transcribe the P22 int gene. We show that this promoter, called P_al, is active both in vivo and in vitro, and is dependent upon the P22 cII-like gene, called c1. We have also determined the DNA sequence of a 3.3 kb segment that closes the gap between previously reported sequences to give a continuous sequence between the P22 p_L promoter and the int gene. The newly determined sequence is densely packed with genes from the p_L direction, and the proteins predicted by the sequence show excellent correlation with the proteins mapped by Youderian and Susskind in 1980. However, the sequence contains no apparent genes in the opposite (p_al) direction, and no additional binding motifs for the P22 c1 protein. We conclude that int gene expression in P22 is regulated by a different mechanism than in λ.     

Do environmental changes or juvenile competition act as mechanisms of species displacement in crayfishes?

The Big Creek Crayfish, Orconectes peruncus, is native to the St. Francis River drainage in Missouri, USA and is often absent where the introduced Woodland Crayfish, Orconectes hylas, has established. We performed a field experiment to determine whether effects of current abiotic conditions and interspecific competition with O. hylas were responsible for displacement of O. peruncus from parts of their former range. We examined growth and survival of juvenile male O. peruncus exposed to juvenile male O. hylas in enclosures at two sites in the former range of O. peruncus. Enclosures contained 8 (low density) or 16 individuals (high density) and had O. peruncus only (control) or both species (interspecific treatment). Juvenile O. peruncus were able to survive and grow in portions of their former range, implicating biotic versus abiotic factors in the displacement of O. peruncus. Survival rates of O. peruncus did not differ among treatments at either site. Orconectes peruncus showed significant growth in all treatments and interspecific effects were not greater than intraspecific effects on O. peruncus growth rates. High-density treatments showed significantly reduced O. peruncus growth rates compared to low-density treatments, except in Carver Creek interspecific treatments. When considered in the context of previous studies examining the effects of O. hylas on O. peruncus, results suggest that neither direct competition between juvenile males of the two species or abiotic change are responsible for the decreased range of O. peruncus. Additional research is required to determine the mechanism(s) driving the displacement of O. peruncus.