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91.
In controlled human infection (CHI) studies, investigators deliberately infect healthy individuals with pathogens in order to study mechanisms of disease or obtain preliminary efficacy data on investigational vaccines and medicines. CHI studies offer a fast and cost-effective way of generating new scientific insights, prioritizing investigational products for clinical testing, and reducing the risk that large numbers of people are exposed to ineffective or harmful substances in research or in practice. Yet depending on the pathogen, CHI studies can involve significant risks or burdens for participants, pose risks to individuals or communities not involved in the research, and lead to public controversy. It is therefore essential to ensure that the risks of CHI studies are justified by their social value—that is, their potential to generate benefits for society—and that public trust can be maintained. In this paper, we aim to clarify how research sponsors, research ethics committees and other reviewers should judge the social value of CHI studies. We develop a list of relevant considerations for making social value judgments based on the standard view of social value. We then use this list to discuss the example of potentially conducting dengue virus CHI studies in endemic settings. We argue that dengue virus CHI studies in endemic settings would fall on the higher end of the spectrum of social value, mostly because of their potential to redirect all fields of future dengue research. Drawing on this discussion, we derive several general recommendations for how reviewers should judge the social value of CHI studies. 相似文献
92.
Marcos Carvalho Borges Luiza Antunes Castro Benedito Antonio Lopes da Fonseca 《Memórias do Instituto Oswaldo Cruz》2013,108(5):596-599
Dengue is the most important arboviral disease in the world. As
chloroquine, an antimalarial agent, has shown some antiviral effects, this study
evaluated its effect in patients with dengue. A randomised, double-blind study
was performed by administering chloroquine or placebo for three days to 129
patients with dengue-related symptoms. Of these patients, 37 were confirmed as
having dengue and completed the study; in total, 19 dengue patients received
chloroquine and 18 received placebo. There was no significant difference in the
duration of the disease or the degree and days of fever. However, 12 patients
(63%) with confirmed dengue reported a substantial decrease in pain intensity
and a great improvement in their ability to perform daily activities (p =
0.0004) while on the medication and the symptoms returned immediately after
these patients stopped taking the medication. The same effect was not observed
in patients with diseases other than dengue. Therefore, this study shows that
patients with dengue treated with chloroquine had an improvement in their
quality of life and were able to resume their daily activities. However, as
chloroquine did not alter the duration of the disease or the intensity and days
of fever, further studies are necessary to confirm the clinical effects and to
assess the side effects of chloroquine in dengue patients. 相似文献
93.
Lindsay P. Campbell Caylor Luther David Moo-Llanes Janine M. Ramsey Rogelio Danis-Lozano A. Townsend Peterson 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2015,370(1665)
Numerous recent studies have illuminated global distributions of human cases of dengue and other mosquito-transmitted diseases, yet the potential distributions of key vector species have not been incorporated integrally into those mapping efforts. Projections onto future conditions to illuminate potential distributional shifts in coming decades are similarly lacking, at least outside Europe. This study examined the global potential distributions of Aedes aegypti and Aedes albopictus in relation to climatic variation worldwide to develop ecological niche models that, in turn, allowed anticipation of possible changes in distributional patterns into the future. Results indicated complex global rearrangements of potential distributional areas, which—given the impressive dispersal abilities of these two species—are likely to translate into actual distributional shifts. This exercise also signalled a crucial priority: digitization and sharing of existing distributional data so that models of this sort can be developed more rigorously, as present availability of such data is fragmentary and woefully incomplete. 相似文献
94.
95.
prM蛋白是登革病毒膜蛋白M的前体,膜蛋白M对病毒的组装与成熟有重要作用,针对prM基因设计的小干扰RNA(siRNA)可短期抑制登革病毒复制.为了达到长期抑制登革病毒的效果,本研究构建了插入prM siRNA序列的重组慢病毒,利用流式细胞术分选以及杀稻瘟霉素抗性,筛选出稳定表达prM siRNA的非洲绿猴肾细胞(Vero细胞)系.经逆转录PCR及测序验证siRNA序列表达正确. Vero细胞中prM siRNA的表达率约为976%.当受到登革病毒攻击时,表达prM siRNA的Vero细胞能够明显抑制登革病毒prM基因的表达,并抑制登革病毒在Vero细胞中的复制.建立的Vero细胞系可用于RNA干扰防治登革病毒感染的进一步应用研究. 相似文献
96.
Le Goff G Revollo J Guerra M Cruz M Barja Simon Z Roca Y Vargas Florès J Hervé JP 《Parasite (Paris, France)》2011,18(3):277-280
The natural transmission of dengue virus from an infected female mosquito to its progeny, namely the vertical transmission, was researched in wild caught Aedes aegypti during an important outbreak in the town of Santa Cruz de la Sierra, Bolivia. Mosquitoes were collected at the preimaginal stages (eggs, larvae and pupae) then reared up to adult stage for viral detection using molecular methods. Dengue virus serotypes 1 and 3 were found to be co-circulating with significant higher prevalence in male than in female mosquitoes. Of the 97 pools of Ae. aegypti (n = 635 male and 748 female specimens) screened, 14 pools, collected in February-May in 2007, were found positive for dengue virus infection: five DEN-1 and nine DEN-3. The average true infection rate (TIR) and minimum infection rate (MIR) were respectively 1.08% and 1.01%. These observations suggest that vertical transmission of dengue virus may be detected in vectors at the peak of an outbreak as well as several months before an epidemic occurs in human population. 相似文献
97.
Although many laboratory studies of intra-specific competition have been conducted with Ae. aegypti, there have been few studies in natural environments and none that examined density dependence in natural containers at normal field densities. Additionally, current mathematical models that predict Ae. aegypti population dynamics lack empirically-based functions for density-dependence. We performed field experiments in Tapachula, Mexico, where dengue is a significant public health concern. Twenty-one containers with natural food and water that already contained larvae were collected from local houses. Each container was divided in half and the naturally occurring larvae were apportioned in a manner that resulted in one side of the container (high density) having four times the density of the second side (low density). Larvae were counted and pupae were removed daily. Once adults emerged, wing span was measured to estimate body size. Density had a significant impact on larval survival, adult body size, and the time taken to transition from 4(th) instar to pupation. Increased density decreased larval survival by 20% and decreased wing length by an average of 0.19 mm. These results provide a starting point for a better understanding of density dependence in field populations of Ae. aegypti. 相似文献
98.
Jill M. Perreira Christopher R. ChinEric M. Feeley Abraham L. Brass 《Journal of molecular biology》2013
The interferon-inducible transmembrane protein (IFITM) family inhibits a growing number of pathogenic viruses, among them influenza A virus, dengue virus, hepatitis C virus, and Ebola virus. This review covers recent developments in our understanding of the IFITM's molecular determinants, potential mechanisms of action, and impact on pathogenesis. 相似文献
99.
Mayara Marques Carneiro da Silva Laura Helena Vega Gonzales Gil Ernesto Torres de Azevedo Marques Júnior Carlos Eduardo Calzavara-Silva 《Memórias do Instituto Oswaldo Cruz》2013,108(6):755-762
Currently, several assays can confirm acute dengue infection at the
point-of-care. However, none of these assays can predict the severity of the
disease symptoms. A prognosis test that predicts the likelihood of a dengue
patient to develop a severe form of the disease could permit more efficient
patient triage and treatment. We hypothesise that mRNA expression of apoptosis
and innate immune response-related genes will be differentially regulated during
the early stages of dengue and might predict the clinical outcome. Aiming to
identify biomarkers for dengue prognosis, we extracted mRNA from the peripheral
blood mononuclear cells of mild and severe dengue patients during the febrile
stage of the disease to measure the expression levels of selected genes by
quantitative polymerase chain reaction. The selected candidate biomarkers were
previously identified by our group as differentially expressed in microarray
studies. We verified that the mRNA coding for CFD, MAGED1, PSMB9, PRDX4 and
FCGR3B were differentially expressed between patients who developed clinical
symptoms associated with the mild type of dengue and patients who showed
clinical symptoms associated with severe dengue. We suggest that this gene
expression panel could putatively serve as biomarkers for the clinical prognosis
of dengue haemorrhagic fever. 相似文献
100.
T. Chouin-Carneiro T. H. Ant C. Herd F. Louis A. B. Failloux S. P. Sinkins 《Medical and veterinary entomology》2020,34(1):116-119
Transinfections of the maternally transmitted endosymbiont Wolbachia pipientis can reduce RNA virus replication and prevent transmission by Aedes aegypti, and also have the capacity to invade wild-type populations, potentially reaching and maintaining high infection frequencies. Levels of virus transmission blocking are positively correlated with Wolbachia intracellular density. Despite reaching high densities in Ae. aegypti, transinfections of wAlbA, a strain native to Aedes albopictus, showed no blocking of Semliki Forest Virus in previous intrathoracic injection challenges. To further characterize wAlbA blocking in Ae. aegypti, adult females were intrathoracically challenged with Zika (ZIKV) and dengue viruses, and then fed a ZIKV-containing bloodmeal. No blocking was observed with either virus when challenged by intrathoracic injection. However, when ZIKV was delivered orally, wAlbA-infected females showed a significant reduction in viral replication and dissemination compared with uninfected controls, as well as a complete absence of virus in saliva. Although other Wolbachia strains have been shown to cause more robust viral blocking in Ae. aegypti, these findings demonstrate that, in principle, wAlbA could be used to reduce virus transmission in this species. Moreover, the results highlight the potential for underestimation of the strength of virus-blocking when based on intrathoracic injection compared with more natural oral challenges. 相似文献