Abstract:
UNLABELLED:CELADEN was a randomized placebo-controlled trial of 50 patients with confirmed dengue fever to evaluate the efficacy and safety of celgosivir (A study registered at ClinicalTrials.gov, number NCT01619969). Celgosivir was given as a 400 mg loading dose and 200 mg bid (twice a day) over 5 days. Replication competent virus was measured by plaque assay and compared to reverse transcription quantitative PCR (qPCR) of viral RNA. Pharmacokinetics (PK) correlations with viremia, immunological profiling, next generation sequence (NGS) analysis and hematological data were evaluated as exploratory endpoints here to identify possible signals of pharmacological activity. Viremia by plaque assay strongly correlated with qPCR during the first four days. Immunological profiling demonstrated a qualitative shift in T helper cell profile during the course of infection. NGS analysis did not reveal any prominent signature that could be associated with drug treatment; however the phylogenetic spread of patients' isolates underlines the importance of strain variability that may potentially confound interpretation of dengue drug trials conducted during different outbreaks and in different countries. Celgosivir rapidly converted to castanospermine (Cast) with mean peak and trough concentrations of 5727 ng/mL (30.2 μM) and 430 ng/mL (2.3 μM), respectively and cleared with a half-life of 2.5 (± 0.6) hr. Mean viral log reduction between day 2 and 4 (VLR2-4) was significantly greater in secondary dengue than primary dengue (p = 0.002). VLR2-4 did not correlate with drug AUC but showed a trend of greater response with increasing Cmin. PK modeling identified dosing regimens predicted to achieve 2.4 to 4.5 times higher Cmin. than in the CELADEN trial for only 13% to 33% increase in overall dose. A small, non-statistical trend towards better outcome on platelet nadir and difference between maximum and minimum hematocrit was observed in celgosivir-treated patients with secondary dengue infection. Optimization of the dosing regimen and patient stratification may enhance the ability of a clinical trial to demonstrate celgosivir activity in treating dengue fever based on hematological endpoints. A new clinical trial with a revised dosing regimen is slated to start in 2016 (NCT02569827). Furthermore celgosivir's potential value for treatment of other flaviruses such as Zika virus should be investigated urgently. TRIAL REGISTRATION:ClinicalTrials.gov NCT01619969.
journal_name
PLoS Negl Trop Disjournal_title
PLoS neglected tropical diseasesauthors
Sung C,Wei Y,Watanabe S,Lee HS,Khoo YM,Fan L,Rathore AP,Chan KW,Choy MM,Kamaraj US,Sessions OM,Aw P,de Sessions PF,Lee B,Connolly JE,Hibberd ML,Vijaykrishna D,Wijaya L,Ooi EE,Low JG,Vasudevan SGdoi
10.1371/journal.pntd.0004851subject
Has Abstractpub_date
2016-08-10 00:00:00pages
e0004851issue
8eissn
1935-2727issn
1935-2735pii
PNTD-D-16-00481journal_volume
10pub_type
临床试验,杂志文章,随机对照试验abstract:INTRODUCTION:Neglected tropical diseases produce an enormous burden on many of the poorest and most disenfranchised populations in sub-Saharan Africa. Similar to other developing areas throughout the world, this region's dearth of skilled health providers renders Western-style primary care efforts to address such disea...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,评审
doi:10.1371/journal.pntd.0004914
更新日期:2016-09-15 00:00:00
abstract:BACKGROUND:Cure after treatment for human African trypanosomiasis (HAT) is assessed by examination of the cerebrospinal fluid every 6 months, for a total period of 2 years. So far, no markers for cure or treatment failure have been identified in blood. Trypanosome-specific antibodies are detectable in blood by the Card...
journal_title:PLoS neglected tropical diseases
pub_type: 临床试验,杂志文章
doi:10.1371/journal.pntd.0000590
更新日期:2010-01-26 00:00:00
abstract:BACKGROUND:The main objective of the study was to determine the degree of sensitization to Anisakis spp. antigens in healthy coastal population of Dalmatia given the high thermally unprocessed fish intake rate present in this area, suggested as a significant risk factor for anisakiasis. We performed a monocenter, cross...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002673
更新日期:2014-02-06 00:00:00
abstract:BACKGROUND:In 2007, a novel bunyavirus was found in Henan Province, China and named fever, thrombocytopenia and leukocytopenia syndrome virus (FTLSV); since then, FTLSV has been found in ticks and animals in many Chinese provinces. Human-to-human transmission has been documented, indicating that FTLSV should be conside...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003237
更新日期:2014-10-16 00:00:00
abstract::In Latin America and the Caribbean, around 195 million people live in poverty, a situation that increases the burden of some infectious diseases. Neglected diseases, in particular, are often restricted to poor, marginalized sections of the population. Tools exist to combat these diseases, making it imperative to work ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0000964
更新日期:2011-02-15 00:00:00
abstract::Rabies is an ancient viral disease that significantly impacts human and animal health throughout the world. In the developing parts of the world, dog bites represent the highest risk of rabies infection to people, livestock, and other animals. However, in North America, where several rabies virus variants currently ci...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,评审
doi:10.1371/journal.pntd.0005249
更新日期:2017-03-16 00:00:00
abstract:BACKGROUND:Visceral leishmaniasis (VL) is characterized by parasite-specific immunosuppression besides an intense pro-inflammatory response. Lipopolisaccharide (LPS) has been implicated in the immune activation of T-cell deficient diseases such as HIV/AIDS and idiopathic lymphocytopenia. The source of LPS is gram-negat...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001198
更新日期:2011-07-01 00:00:00
abstract::Mosquito-borne diseases continue to remain major threats to human and animal health and impediments to socioeconomic development. Increasing mosquito resistance to chemical insecticides is a great public health concern, and new strategies/technologies are necessary to develop the next-generation of vector control tool...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003735
更新日期:2015-05-21 00:00:00
abstract::The immunomodulatory properties of lipophosphoglycans (LPG) from New World species of Leishmania have been assessed in Leishmania infantum and Leishmania braziliensis, the causative agents of visceral and cutaneous leishmaniasis, respectively. This glycoconjugate is highly polymorphic among species with variation in s...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004848
更新日期:2016-08-10 00:00:00
abstract:BACKGROUND:Previous studies investigating the role of cytokines in the pathogenesis of leprosy have either been on only small numbers of patients or have not combined clinical and histological data. The INFIR Cohort study is a prospective study of 303 new multibacillary leprosy patients to identify risk factors for rea...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001327
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:Most of the Leishmania genome is reported to be constitutively expressed during the life cycle of the parasite, with a few regulated genes. Inter-species comparative transcriptomics evidenced a low number of species-specific differences related to differentially distributed genes or the differential regulati...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001021
更新日期:2011-05-10 00:00:00
abstract::Mycetoma, one of the badly neglected tropical diseases, it is a localised chronic granulomatous inflammatory disease characterised by painless subcutaneous mass and formation of multiple sinuses that produce purulent discharge and grains. If untreated early and appropriately, it usually spread to affect the deep struc...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006391
更新日期:2018-05-10 00:00:00
abstract::In the current study, a comprehensive, data driven, mathematical model for cholera transmission in Haiti is presented. Along with the inclusion of short cycle human-to-human transmission and long cycle human-to-environment and environment-to-human transmission, this novel dynamic model incorporates both the reported c...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004153
更新日期:2015-10-21 00:00:00
abstract::Salmonella Typhimurium sequence type (ST) 313 produces septicemia in infants in sub-Saharan Africa. Although there are known genetic and phenotypic differences between ST313 strains and gastroenteritis-associated ST19 strains, conflicting data about the in vivo virulence of ST313 strains have been reported. To resolve...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005697
更新日期:2017-08-04 00:00:00
abstract:BACKGROUND:Little information is available about infantile visceral leishmaniasis (VL) in Albania as regards incidence, diagnosis and management of the disease. METHODOLOGY/PRINCIPAL FINDINGS:Demographic data, clinical and laboratory features and therapeutic findings were considered in children admitted to University ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0000814
更新日期:2010-09-07 00:00:00
abstract:BACKGROUND:Buruli ulcer is a chronic ulcerating skin condition, with the highest burden found in Central and West Africa where it disproportionately affects the most vulnerable populations. Treatment is demanding, comprising eight-weeks of daily antibiotics, regular wound care and possible surgical intervention. Treatm...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008369
更新日期:2020-05-26 00:00:00
abstract:BACKGROUND:Rodents are major reservoirs of pathogens responsible for numerous zoonotic diseases in humans and livestock. Assessing their microbial diversity at both the individual and population level is crucial for monitoring endemic infections and revealing microbial association patterns within reservoirs. Recently, ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003929
更新日期:2015-08-18 00:00:00
abstract:BACKGROUND:Melioidosis is a severe bacterial infection caused by Burkholderia pseudomallei with a high case-fatality rate. Epidemiological and animal studies show the possibility of inhalation transmission. However, no B. pseudomallei concentrations in ambient air have been researched. Here, we developed a method to qu...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002877
更新日期:2014-05-29 00:00:00
abstract::Leprosy is an infectious disease caused by Mycobacterium leprae and frequently resulting in irreversible deformities and disabilities. Ticks play an important role in infectious disease transmission due to their low host specificity, worldwide distribution, and the biological ability to support transovarial transmissi...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007001
更新日期:2018-12-19 00:00:00
abstract:BACKGROUND:Severe fever with thrombocytopenia syndrome virus (SFTSV), the causative agent for the fatal life-threatening infectious disease, severe fever with thrombocytopenia syndrome (SFTS), was first identified in the central and eastern regions of China. Although the viral RNA was detected in free-living and parasi...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004092
更新日期:2015-10-20 00:00:00
abstract:BACKGROUND:Although infection with Trypanosoma cruzi is thought to be lifelong, less than half of those infected develop cardiomyopathy, suggesting greater parasite control or even clearance. Antibody levels appear to correlate with T. cruzi (antigen) load. We test the association between a downwards antibody trajector...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008787
更新日期:2020-10-27 00:00:00
abstract:BACKGROUND:Melioidosis is a tropical infectious disease associated with significant mortality due to early onset of sepsis. OBJECTIVE:We sought to review case reports of melioidosis from Malaysia. METHODS:We conducted a computerized search of literature resources including PubMed, OVID, Scopus, MEDLINE and the COCHRA...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,评审
doi:10.1371/journal.pntd.0005182
更新日期:2016-12-22 00:00:00
abstract::Hand, foot and mouth disease (HFMD) continues to challenge Asia with pandemic potential. In Vietnam, there have been two major outbreaks occurring during 2011-2012 (>200,000 hospitalizations and >200 deaths) and more recently in 2018 (>130,000 hospitalizations and 17 deaths). Given the high burden and the complex epid...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008544
更新日期:2020-08-17 00:00:00
abstract:OBJECTIVES:Burkholderia pseudomallei, the causative agent for melioidosis, has become a public health problem in India and across the world. Melioidosis can be difficult to diagnose because of the inconsistent clinical presentations of the disease. This study aims to determine the genetic diversity among the clinical i...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006558
更新日期:2018-06-27 00:00:00
abstract::The evolutionary history and age of Plasmodium vivax has been inferred as both recent and ancient by several studies, mainly using mitochondrial genome diversity. Here we address the age of P. vivax on the Indian subcontinent using selectively neutral housekeeping genes and tandem repeat loci. Analysis of ten housekee...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002425
更新日期:2013-09-19 00:00:00
abstract::Clinical manifestations in onchocerciasis range from generalized onchocerciasis (GEO) to the rare but severe hyperreactive (HO)/sowda form. Since disease pathogenesis is associated with host inflammatory reactions, we investigated whether Th17 responses could be related to aggravated pathology in HO. Using flow cytome...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003414
更新日期:2015-01-08 00:00:00
abstract::Trypanosoma cruzi is exposed during its life to exogenous and endogenous oxidative stress, leading to damage of several macromolecules such as DNA. There are many DNA repair pathways in the nucleus and mitochondria (kinetoplast), where specific protein complexes detect and eliminate damage to DNA. One group of these p...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006220
更新日期:2018-02-12 00:00:00
abstract::Glossina (G.) spp. (Diptera: Glossinidae), known as tsetse flies, are vectors of African trypanosomes that cause sleeping sickness in humans and nagana in domestic livestock. Knowledge on tsetse distribution and accurate species identification help identify potential vector intervention sites. Morphological species id...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002305
更新日期:2013-07-11 00:00:00
abstract::The area of Walikale in North Kivu, Democratic Republic of Congo, is intensely affected by conflict and population displacement. Médecins-Sans-Frontières (MSF) returned to provide primary healthcare in July 2012. To better understand the impact of the ongoing conflict and displacement on the population, a retrospectiv...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003181
更新日期:2014-09-18 00:00:00
abstract::Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) that recently caused outbreaks in the Americas. Over the past 60 years, this virus has been observed circulating among African, Asian, and Pacific Island populations, but little attention has been paid by the scientific community until the discovery that large-...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,评审
doi:10.1371/journal.pntd.0005933
更新日期:2017-11-16 00:00:00