High sensitivity detection of Plasmodium species reveals positive correlations between infections of different species, shifts in age distribution and reduced local variation in Papua New Guinea

BACKGROUND: When diagnosed by standard light microscopy (LM), malaria prevalence can vary significantly between sites, even at local scale, and mixed species infections are consistently less common than expect in areas co-endemic for Plasmodium falciparum, Plasmodium vivax and Plasmodium malariae. The development of a high-throughput molecular species diagnostic assay now enables routine PCR-based surveillance of malaria infections in large field and intervention studies, and improves resolution of species distribution within and between communities. METHODS: This study reports differences in the prevalence of infections with all four human malarial species and of mixed infections as diagnosed by LM and post-PCR ligase detection reaction-fluorescent microsphere (LDR-FMA) assay in 15 villages in the central Sepik area of Papua New Guinea. RESULTS: Significantly higher rates of infection by P. falciparum, P. vivax, P. malariae and Plasmodium ovale were observed in LDR-FMA compared to LM diagnosis (p > 0.001). Increases were particularly pronounced for P. malariae (3.9% vs 13.4%) and P. ovale (0.0% vs 4.8%). In contrast to LM diagnosis, which suggested a significant deficit of mixed species infections, a significant excess of mixed infections over expectation was detected by LDR-FMA (p > 0.001). Age of peak prevalence shifted to older age groups in LDR-FMA diagnosed infections for P. falciparum (LM: 7-9 yrs 47.5%, LDR-FMA: 10-19 yrs 74.2%) and P. vivax (LM: 4-6 yrs 24.2%, LDR-FMA: 7-9 yrs 50.9%) but not P. malariae infections (10-19 yrs, LM: 7.7% LDR-FMA: 21.6%). Significant geographical variation in prevalence was found for all species (except for LM-diagnosed P. falciparum), with the extent of this variation greater in LDR-FMA than LM diagnosed infections (overall, 84.4% vs. 37.6%). Insecticide-treated bednet (ITN) coverage was also the dominant factor linked to geographical differences in Plasmodium species infection prevalence explaining between 60.6% - 74.5% of this variation for LDR-FMA and 81.8% - 90.0% for LM (except P. falciparum), respectively. CONCLUSION: The present study demonstrates that application of molecular diagnosis reveals patterns of malaria risk that are significantly different from those obtained by standard LM. Results provide insight relevant to design of malaria control and eradication strategie

Linear ramps of the mass in the O(N) model: Dynamical transition and quantum noise of excitations

Nonthermal dynamical critical behavior can arise in isolated quantum systems brought out of equilibrium by a change in time of their parameters. While this phenomenon has been studied in a variety of systems in the case of a sudden quench, we consider here its sensitivity to a change of protocol by considering the experimentally relevant case of a linear ramp in time. Focusing on the O(N) model in the large-N limit, we will show that a dynamical phase transition is always present for all durations of the ramp, and we discuss the crossover between the sudden quench transition and one dominated by the equilibrium quantum critical point. We show that the critical behavior of the statistics of the excitations, signaling the nonthermal nature of the transition, is also robust. An intriguing crossover in the equal-time correlation function, related to an anomalous coarsening, is also discussed. \ua9 2016 American Physical Society

"Whenever they cry, I cry with them”: Reciprocal relationships and the role of ethics in a verbal autopsy study in Papua New Guinea

Verbal autopsy (VA) methods usually involve an interview with a recently bereaved individual to ascertain the most probable cause of death when a person dies outside of a hospital and/or did not receive a reliable death certificate. A number of concerns have arisen around the ethical and social implications of the use of these methods. In this paper we examine these concerns, looking specifically at the cultural factors surrounding death and mourning in Papua New Guinea, and the potential for VA interviews to cause emotional distress in both the bereaved respondent and the VA fieldworker. Thirty one semi-structured interviews with VA respondents, the VA team and community relations officers as well as observations in the field and team discussions were conducted between June 2013 and August 2014. While our findings reveal that VA participants were often moved to cry and feel sad, they also expressed a number of ways they benefited from the process, and indeed welcomed longer transactions with the VA interviewers. Significantly, VA interviewers, who have hitherto been largely neglected in the literature, highlights the ways in which fieldworkers navigate transactions with the participants and make everyday decisions about their relationships with them in order to ensure that they and VA interviews are accepted by the community. The role of the VA fieldworker should be more carefully considered, as should the implications for training and institutional support that follow

Neutrophil a-defensins promote thrombosis in vivo by altering fibrin formation, structure, and stability

© 2019 by The American Society of Hematology. Inflammation and thrombosis are integrated, mutually reinforcing processes, but the interregulatory mechanisms are incompletely defined. Here, we examined the contribution of a-defensins (a-defs), antimicrobial proteins released from activated human neutrophils, on clot formation in vitro and in vivo. Activation of the intrinsic pathway of coagulation stimulates release of a-defs from neutrophils. a-Defs accelerate fibrin polymerization, increase fiber density and branching, incorporate into nascent fibrin clots, and impede fibrinolysis in vitro. Transgenic mice (Def 11 ) expressing human a-Def-1 developed larger, occlusive, neutrophil-rich clots after partial inferior vena cava (IVC) ligation than those that formed in wild-type (WT) mice. IVC thrombi extracted from Def 11 mice were composed of a fibrin meshwork that was denser and contained a higher proportion of tightly packed compressed polyhedral erythrocytes than those that developed in WT mice. Def 11 mice were resistant to thromboprophylaxis with heparin. Inhibiting activation of the intrinsic pathway of coagulation, bone marrow transplantation from WT mice or provision of colchicine to Def 11 mice to inhibit neutrophil degranulation decreased plasma levels of a-defs, caused a phenotypic reversion characterized by smaller thrombi comparable to those formed in WT mice, and restored responsiveness to heparin. These data identify a-defs as a potentially important and tractable link between innate immunity and thrombosis

Neutrophil a-defensins promote thrombosis in vivo by altering fibrin formation, structure, and stability

© 2019 by The American Society of Hematology. Inflammation and thrombosis are integrated, mutually reinforcing processes, but the interregulatory mechanisms are incompletely defined. Here, we examined the contribution of a-defensins (a-defs), antimicrobial proteins released from activated human neutrophils, on clot formation in vitro and in vivo. Activation of the intrinsic pathway of coagulation stimulates release of a-defs from neutrophils. a-Defs accelerate fibrin polymerization, increase fiber density and branching, incorporate into nascent fibrin clots, and impede fibrinolysis in vitro. Transgenic mice (Def 11 ) expressing human a-Def-1 developed larger, occlusive, neutrophil-rich clots after partial inferior vena cava (IVC) ligation than those that formed in wild-type (WT) mice. IVC thrombi extracted from Def 11 mice were composed of a fibrin meshwork that was denser and contained a higher proportion of tightly packed compressed polyhedral erythrocytes than those that developed in WT mice. Def 11 mice were resistant to thromboprophylaxis with heparin. Inhibiting activation of the intrinsic pathway of coagulation, bone marrow transplantation from WT mice or provision of colchicine to Def 11 mice to inhibit neutrophil degranulation decreased plasma levels of a-defs, caused a phenotypic reversion characterized by smaller thrombi comparable to those formed in WT mice, and restored responsiveness to heparin. These data identify a-defs as a potentially important and tractable link between innate immunity and thrombosis

Aging and coarsening in isolated quantum systems after a quench: Exact results for the quantum O(N) model with N -> infinity

The nonequilibrium dynamics of an isolated quantum system after a sudden quench to a dynamical critical point is expected to be characterized by scaling and universal exponents due to the absence of time scales. We explore these features for a quench of the parameters of a Hamiltonian with O(N) symmetry, starting from a ground state in the disordered phase. In the limit of infinite N, the exponents and scaling forms of the relevant two-time correlation functions can be calculated exactly. Our analytical predictions are confirmed by the numerical solution of the corresponding equations. Moreover, we find that the same scaling functions, yet with different exponents, also describe the coarsening dynamics for quenches below the dynamical critical point