Abstract:
BACKGROUND:The genus Trichuris includes parasites of major relevance in veterinary and human medicine. Despite serious economic losses and enormous impact on public health, treatment options against whipworms are very limited. Additionally, there is an obvious lack of appropriately characterized experimental infection models. Therefore, a detailed parasitological characterization of a Trichuris muris isolate was performed in C57BL/10 mice. Subsequently, the in vivo efficacies of the aminophenylamidines amidantel, deacylated amidantel (dAMD) and tribendimidine as well as the cyclooctadepsipeptides emodepside and in particular PF1022A were analyzed. This was performed using various administration routes and treatment schemes targeting histotropic and further developed larval as well as immature and mature adult stages. METHODOLOGY/PRINCIPAL FINDINGS:Duration of prepatent period, time-dependent localization of larvae during period of prepatency as well as the duration of patency of the infection were determined before drugs were tested in the characterized trichurosis model. Amidantel showed no effect against mature adult T. muris. Tribendimidine showed significantly higher potency than dAMD after oral treatments (ED50 values of 6.5 vs. 15.1 mg/kg). However, the opposite was found for intraperitoneal treatments (ED50 values of 15.3 vs. 8.3 mg/kg). When emodepside and PF1022A were compared, the latter was significantly less effective against mature adults following intraperitoneal (ED50 values of 6.1 vs. 55.7 mg/kg) or subcutaneous (ED50 values of 15.2 vs. 225.7 mg/kg) administration. Only minimal differences were observed following oral administration (ED50 values of 2.7 vs. 5.2 mg/kg). Triple and most single oral doses with moderate to high dosages of PF1022A showed complete efficacy against histotropic second stage larvae (3 × 100 mg/kg or 1 × 250 mg/kg), further developed larvae (3 × 10 mg/kg or 1 × 100 mg/kg) and immature adults (3 × 10 mg/kg or 1×100 mg/kg). Histotropic first stage larvae were only eliminated after three doses of PF1022A (3 × 100 mg/kg) but not after a single dose. CONCLUSIONS/SIGNIFICANCE:These results indicate that the cyclooctadepsipeptides are a drug class with promising candidates for further evaluation for the treatment of trichurosis of humans and livestock animals in single dose regimens.
journal_name
PLoS Negl Trop Disjournal_title
PLoS neglected tropical diseasesauthors
Kulke D,Krücken J,Harder A,von Samson-Himmelstjerna Gdoi
10.1371/journal.pntd.0002698subject
Has Abstractpub_date
2014-02-20 00:00:00pages
e2698issue
2eissn
1935-2727issn
1935-2735pii
PNTD-D-13-01051journal_volume
8pub_type
杂志文章abstract::The interaction between Plasmodium vivax Duffy binding protein (PvDBP) and Duffy antigen receptor for chemokines (DARC) has been described as critical for the invasion of human reticulocytes, although increasing reports of P. vivax infections in Duffy-negative individuals questions its unique role. To investigate the ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006555
更新日期:2018-10-22 00:00:00
abstract::Dengue virus and its four serotypes (DENV-1 to DENV-4) infect 390 million people and are implicated in at least 25,000 deaths annually, with the largest disease burden in tropical and subtropical regions. We investigated the spatial dynamics of DENV-1, DENV-2 and DENV-3 in Brazil by applying a statistical framework to...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002769
更新日期:2014-04-17 00:00:00
abstract:BACKGROUND:Dengue is the most prevalent arthropod-borne viral illness in humans with half of the world's population at risk. During early infancy, severe dengue can develop after a primary dengue virus infection. There has been a clinical observation that severe dengue during the first year of life is seen only in chub...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004267
更新日期:2015-12-04 00:00:00
abstract:BACKGROUND:A family of hydrophilic acylated surface (HASP) proteins, containing extensive and variant amino acid repeats, is expressed at the plasma membrane in infective extracellular (metacyclic) and intracellular (amastigote) stages of Old World Leishmania species. While HASPs are antigenic in the host and can induc...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0000829
更新日期:2010-09-28 00:00:00
abstract::Theileria parva is an economically important, intracellular, tick-transmitted parasite of cattle. A live vaccine against the parasite is effective against challenge from cattle-transmissible T. parva but not against genotypes originating from the African Cape buffalo, a major wildlife reservoir, prompting the need to ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008781
更新日期:2020-10-29 00:00:00
abstract:BACKGROUND:Burkholderia cepacia complex (Bcc) is a group of serious pathogens in cystic fibrosis patients and causes life threatening infections in immunocompromised patients. Species within the Bcc are widely distributed within the environment, can survive in the presence of disinfectants and antiseptics, and are inhe...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008200
更新日期:2020-04-09 00:00:00
abstract::Host and parasite gene expression in skin biopsies from Leishmania braziliensis-infected patients were simultaneously analyzed using high throughput RNA-sequencing. Biopsies were taken from 8 patients with early cutaneous leishmaniasis and 17 patients with late cutaneous leishmaniasis. Although parasite DNA was found ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004992
更新日期:2016-09-15 00:00:00
abstract::Disseminated disease from non-typhoidal Salmonella enterica strains results in >20% mortality globally. Barriers to effective treatment include emerging multidrug resistance, antibiotic treatment failure, and risk factors such as malnutrition and related micronutrient deficiencies. Individuals in sub-Saharan Africa ar...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008737
更新日期:2020-10-02 00:00:00
abstract:BACKGROUND:Mass azithromycin distribution reduces under-5 child mortality. Trachoma control programs currently treat infants aged 6 months and older. Here, we report findings from an infant adverse event survey in 1-5 month olds who received azithromycin as part of a large community-randomized trial in Niger. METHODS ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,随机对照试验
doi:10.1371/journal.pntd.0006950
更新日期:2018-11-12 00:00:00
abstract::West Nile Fever is a zoonotic disease caused by a mosquito-borne flavivirus, WNV. By its clinical sensitivity to the disease, the horse is a useful sentinel of infection. Because of the virus' low-level, short-term viraemia in horses, the primary tools used to diagnose WNV are serological tests. Inter-laboratory profi...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005936
更新日期:2017-09-15 00:00:00
abstract::Schistosomes are human pathogens causing the neglected tropical disease schistosomiasis, which occurs worldwide in (sub-)tropical regions. This infectious disease is often associated with poverty, and more than 700 million people are at risk of infection. Exploitation of novel habitats and limited therapeutic options ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008145
更新日期:2020-05-13 00:00:00
abstract:BACKGROUND:Aedes control interventions are considered the cornerstone of dengue control programmes, but there is scarce evidence on their effect on disease. We set-up a cluster randomized controlled trial in Santiago de Cuba to evaluate the entomological and epidemiological effectiveness of periodical intra- and peri-d...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,随机对照试验
doi:10.1371/journal.pntd.0006031
更新日期:2017-11-08 00:00:00
abstract:BACKGROUND:Typhoid fever, caused by the Gram-negative bacterium Salmonella enterica serovar Typhi, is a major cause of community-acquired bacteremia and death worldwide. S100A8 (MRP8) and S100A9 (MRP14) form bioactive antimicrobial heterodimers (calprotectin) that can activate Toll-like receptor 4, promoting lethal, en...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003663
更新日期:2015-04-10 00:00:00
abstract::Intracerebral microhemorrhages (CMHs) are small foci of hemorrhages in the cerebrum. Acute infections induced by some intracellular pathogens, including rickettsia, can result in CMHs. Annexin a2 (ANXA2) has been documented to play a functional role during intracellular bacterial adhesion. Here we report that ANXA2-kn...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007960
更新日期:2020-07-20 00:00:00
abstract:BACKGROUND:Hantaan virus (HTNV) causes a severe lethal haemorrhagic fever with renal syndrome (HFRS) in humans. Despite a limited understanding of the pathogenesis of HFRS, the importance of the abundant production of pro-inflammatory cytokines has been widely recognized. Interleukin 33 (IL-33) has been demonstrated to...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003514
更新日期:2015-02-06 00:00:00
abstract::Schistosomes are parasitic platyhelminths that currently infect over 200 million people globally. The parasites can live for years in a putatively hostile environment - the blood of vertebrates. We have hypothesized that the unusual schistosome tegument (outer-covering) plays a role in protecting parasites in the bloo...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001011
更新日期:2011-04-05 00:00:00
abstract:BACKGROUND:In Latin America, there are 13 geographically isolated endemic foci distributed among Mexico, Guatemala, Colombia, Venezuela, Brazil and Ecuador. The communities of the three endemic foci found within Mexico have been receiving ivermectin treatment since 1989. In this study, we predicted the trend of occurre...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002033
更新日期:2013-01-01 00:00:00
abstract::Post-kala-azar dermal leishmaniasis (PKDL) is clinical outcome of visceral leishmaniasis (VL) and is thought to be the potential reservoir of parasite. Miltefosine (MF) is the only oral drug existing for treatment of post-kala-azar dermal leishmaniasis (PKDL). Increased miltefosine tolerance in clinical isolates of Le...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008052
更新日期:2020-03-23 00:00:00
abstract:INTRODUCTION:Previous studies of Ebola Virus Disease (EVD) have focused on clinical symptoms and Ebola virus (EBOV) cycle threshold (CT) values recorded at patient triage. Our study explores EVD symptoms and EBOV CT values from onset of illness to recovery or death in a diverse population of patients. METHODOLOGY/PRIN...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005700
更新日期:2017-07-19 00:00:00
abstract:OBJECTIVE:The aim of the study is to examine the spatiotemporal pattern of Japanese Encephalitis (JE) in mainland China during 2002-2010. Specific objectives of the study were to quantify the temporal variation in incidence of JE cases, to determine if clustering of JE cases exists, to detect high risk spatiotemporal c...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002285
更新日期:2013-06-20 00:00:00
abstract:BACKGROUND:Syphilis is resurgent in many regions of the world. Molecular typing is a robust tool for investigating strain diversity and epidemiology. This study aimed to review original research on molecular typing of Treponema pallidum (T. pallidum) with three objectives: (1) to determine specimen types most suitable ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,meta分析,评审
doi:10.1371/journal.pntd.0001273
更新日期:2011-11-01 00:00:00
abstract::Infection with filarial parasites is associated with T cell hyporesponsiveness, which is thought to be partly mediated by their ability to induce regulatory T cells (Tregs) during human infections. This study investigates the functional capacity of Tregs from different groups of filarial patients to suppress filaria-s...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001655
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Human alveolar echinococcosis (AE) is known to be common in certain rural communities in China whilst it is generally rare and sporadic elsewhere. The objective of this study was to provide a first estimate of the global incidence of this disease by country. The second objective was to estimate the global di...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,评审
doi:10.1371/journal.pntd.0000722
更新日期:2010-06-22 00:00:00
abstract::Filoviruses such as Ebola virus (EBOV) cause outbreaks of viral hemorrhagic fevers for which no FDA-approved vaccines or drugs are available. The 2014-2016 EBOV outbreak in West Africa infected approximately 30,000 people, killing more than 11,000 and affecting thousands more in areas still suffering from the effects ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007614
更新日期:2019-07-22 00:00:00
abstract::Fasciolosis caused by Fasciola gigantica is a neglected tropical disease but a constraint on the growth and productivity of cattle, buffaloes and sheep in the tropical countries of Asia and Africa. Resistance to commonly used anthelmintics in Fasciola has increased the need to search for alternative therapeutic target...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006109
更新日期:2017-12-12 00:00:00
abstract:BACKGROUND:Scabies is a disease of worldwide significance, causing considerable morbidity in both humans and other animals. The scabies mite Sarcoptes scabiei burrows into the skin of its host, obtaining nutrition from host skin and blood. Aspartic proteases mediate a range of diverse and essential physiological functi...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002525
更新日期:2013-11-07 00:00:00
abstract::Thromboembolic events were described in patients with Chagas disease without cardiomyopathy. We aim to confirm if there is a hypercoagulable state in these patients and to determine if there is an early normalization of hemostasis factors after antiparasitic treatment. Ninety-nine individuals from Chagas disease-endem...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004269
更新日期:2016-01-04 00:00:00
abstract:BACKGROUND:Melioidosis, a fatal infectious disease caused by Burkholderia pseudomallei, is increasingly diagnosed in tropical regions. However, data on risk factors and the geographic epidemiology of the disease are still limited. Previous studies have also largely been based on the analysis of case series data. Here, ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007243
更新日期:2019-03-18 00:00:00
abstract:BACKGROUND:Entomological indicators are considered key metrics to document the interruption of transmission of Onchocerca volvulus, the etiological agent of human onchocerciasis. Human landing collection is the standard employed for collection of the vectors for this parasite. Recent studies reported the development of...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003450
更新日期:2015-01-08 00:00:00
abstract::Human head lice are blood-sucking insects causing an infestation in humans called pediculosis capitis. The infestation is more prevalent in the school-aged population. Scalp itching, a common presenting symptom, results in scratching and sleep disturbance. The condition can lead to social stigmatization which can lead...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008955
更新日期:2020-12-16 00:00:00