Abstract:
:The predominant mechanism of drug resistance in African trypanosomes is decreased drug uptake due to loss-of-function mutations in the genes for the transporters that mediate drug import. The role of transporters as determinants of drug susceptibility is well documented from laboratory-selected Trypanosoma brucei mutants. But clinical isolates, especially of T. b. gambiense, are less amenable to experimental investigation since they do not readily grow in culture without prior adaptation. Here we analyze a selected panel of 16 T. brucei ssp. field isolates that (i) have been adapted to axenic in vitro cultivation and (ii) mostly stem from treatment-refractory cases. For each isolate, we quantify the sensitivity to melarsoprol, pentamidine, and diminazene, and sequence the genomic loci of the transporter genes TbAT1 and TbAQP2. The former encodes the well-characterized aminopurine permease P2 which transports several trypanocides including melarsoprol, pentamidine, and diminazene. We find that diminazene-resistant field isolates of T. b. brucei and T. b. rhodesiense carry the same set of point mutations in TbAT1 that was previously described from lab mutants. Aquaglyceroporin 2 has only recently been identified as a second transporter involved in melarsoprol/pentamidine cross-resistance. Here we describe two different kinds of TbAQP2 mutations found in T. b. gambiense field isolates: simple loss of TbAQP2, or loss of wild-type TbAQP2 allele combined with the formation of a novel type of TbAQP2/3 chimera. The identified mutant T. b. gambiense are 40- to 50-fold less sensitive to pentamidine and 3- to 5-times less sensitive to melarsoprol than the reference isolates. We thus demonstrate for the first time that rearrangements of the TbAQP2/TbAQP3 locus accompanied by TbAQP2 gene loss also occur in the field, and that the T. b. gambiense carrying such mutations correlate with a significantly reduced susceptibility to pentamidine and melarsoprol.
journal_name
PLoS Negl Trop Disjournal_title
PLoS neglected tropical diseasesauthors
Graf FE,Ludin P,Wenzler T,Kaiser M,Brun R,Pyana PP,Büscher P,de Koning HP,Horn D,Mäser Pdoi
10.1371/journal.pntd.0002475subject
Has Abstractpub_date
2013-10-10 00:00:00pages
e2475issue
10eissn
1935-2727issn
1935-2735pii
PNTD-D-13-00953journal_volume
7pub_type
杂志文章abstract:BACKGROUND:The objectives of this study were to 1) evaluate the influence of treatment with praziquantel on the inflammatory milieu in maternal, placental, and cord blood, 2) assess the extent to which proinflammatory signatures in placental and cord blood impacts birth outcomes, and 3) evaluate the impact of other hel...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,随机对照试验
doi:10.1371/journal.pntd.0007371
更新日期:2019-06-12 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:BACKGROUND:In India, dengue disease is emerging as the most important vector borne public health problem due to rapid and unplanned urbanization, high human density and week management of the disease. Clinical cases are grossly underreported and not much information is available on prevalence and incidence of the disea...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006657
更新日期:2018-08-06 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pntd.0005125.]. ...
journal_title:PLoS neglected tropical diseases
pub_type: 已发布勘误
doi:10.1371/journal.pntd.0005328
更新日期:2017-01-31 00:00:00
abstract:BACKGROUND:Trichinellosis is a serious zoonositc parasitosis worldwide. Because its clinical manifestations aren't specific, the diagnosis of trichinellosis is not easy to be made. Trichinella spiralis muscle larva (ML) excretory-secretory (ES) antigens are the most widely applied diagnostic antigens for human trichine...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006485
更新日期:2018-05-14 00:00:00
abstract::Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly co...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,评审
doi:10.1371/journal.pntd.0002382
更新日期:2013-11-07 00:00:00
abstract:BACKGROUND:Global deworming programs aim to reach 75% of at-risk preschool-age children (pre-SAC) by 2020. The 2013 global pre-SAC deworming coverage initially published by the World Health Organization (WHO) was 23.9%, but this estimate inadequately captured deworming delivered through Child Health Day (CHD) platforms...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004206
更新日期:2015-11-06 00:00:00
abstract:BACKGROUND:Transmission of dengue virus (DENV) from humans to mosquitoes represents a critical component of dengue epidemiology. Examinations of this process have generally been hampered by a lack of methods that adequately represent natural acquisition of DENV by mosquitoes from humans. In this study, we assessed arti...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007116
更新日期:2019-02-12 00:00:00
abstract:BACKGROUND:Dengue is one of the most serious and rapidly spreading arboviral diseases in the world. Despite many acute febrile illnesses in Ethiopia, the burden of illness due to dengue in the country is largely unknown. Thus, the present study aimed to provide the first baseline data on seroprevalence and associated r...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006430
更新日期:2018-05-31 00:00:00
abstract::Wolbachia bacteria are now being introduced into Aedes aegypti mosquito populations for dengue control. When Wolbachia infections are at a high frequency, they influence the local transmission of dengue by direct virus blocking as well as deleterious effects on vector mosquito populations. However, the effectiveness o...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007357
更新日期:2019-04-19 00:00:00
abstract:BACKGROUND:Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is an emerging cause of pneumonia-derived sepsis in the tropics. The gut microbiota supports local mucosal immunity and is increasingly recognized as a protective mediator in host defenses against systemic infection. Here, we aimed...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005548
更新日期:2017-04-19 00:00:00
abstract:BACKGROUND:Aedes aegypti, vector of dengue, chikungunya and Zika viruses, is found at high densities in tropical urban areas. The dissemination of this vector is partially the consequence of failures in current vector control methods, still mainly relying upon insecticides. In the State of São Paulo (SP), Brazil, publi...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006390
更新日期:2018-03-30 00:00:00
abstract:INTRODUCTION:Chikungunya is an emerging public health problem in tropical and subtropical regions, due to ongoing transmission and its incapacitating acute disease phase, and chronic sequelae. The disease is responsible for a major impact on Health Related Quality of Life (HRQoL), which may last several years. To our k...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005987
更新日期:2017-10-09 00:00:00
abstract::The present study aims to investigate how the social context contributes to the prognosis of Chagas disease (CD). This is a multilevel study that considered individual and contextual data. Individual data came from a Brazilian cohort study that followed 1,637 patients who lived in 21 municipalities to which CD is ende...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008399
更新日期:2020-06-29 00:00:00
abstract::The yellow fever vaccines (YF-17D-204 and 17DD) are considered to be among the safest vaccines and the presence of neutralizing antibodies is correlated with protection, although other immune effector mechanisms are known to be involved. T-cell responses are known to play an important role modulating antibody producti...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001938
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Patients with New World cutaneous leishmaniasis (NWCL) caused by Leishmania Viannia are treated with parenteral sodium stibogluconate (SbV) to reduce the risk of development of mucocutanous leishmaniasis. Our centre manages patients with NWCL on an outpatient-basis. This study was conducted to assess the saf...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001688
更新日期:2012-01-01 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::Rabies is a zoonotic infectious disease of the central nervous system (CNS). In unvaccinated or untreated subjects, rabies virus infection causes severe neurological symptoms and is invariably fatal. Despite the long-standing existence of effective vaccines, vaccine availability remains insufficient, with high numbers...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004746
更新日期:2016-06-23 00:00:00
abstract::Mycobacterium leprae (M. leprae) is a human pathogen and the causative agent for leprosy, a chronic disease characterized by lesions of the skin and peripheral nerve damage. Zoonotic transmission of M. leprae to humans by nine-banded armadillos (Dasypus novemcinctus) has been shown to occur in the southern United Stat...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006532
更新日期:2018-06-28 00:00:00
abstract:OBJECTIVE:In some Pacific Island countries, such as Solomon Islands and Fiji, active trachoma is common, but ocular Chlamydia trachomatis (Ct) infection and trachomatous trichiasis (TT) are rare. On Tarawa, the most populous Kiribati island, both the active trachoma sign "trachomatous inflammation-follicular" (TF) and ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005863
更新日期:2017-09-12 00:00:00
abstract::Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neu...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001188
更新日期:2011-06-01 00:00:00
abstract:BACKGROUND:Tick feeding causes extreme morbidity and mortality to humans through transmission of pathogens and causes severe economic losses to the agricultural industry by reducing livestock yield. Salivary gland secretions are essential for tick feeding and thus, reducing or preventing saliva secretions into the vert...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007153
更新日期:2019-02-07 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
abstract::Mosquito-borne chikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus from the genus Alphavirus, family Togaviridae, which causes fever, rash and severe persistent polyarthralgia in humans. Since there are currently no FDA licensed vaccines or antiviral therapies for CHIKV, the development of vaccine...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002719
更新日期:2014-02-20 00:00:00
abstract::Leprosy is a curable neglected disease of humans caused by Mycobacterium leprae that affects the skin and peripheral nerves and manifests clinically in various forms ranging from self-resolving, tuberculoid leprosy to lepromatous leprosy having significant pathology with ensuing disfiguration disability and social sti...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003405
更新日期:2014-12-18 00:00:00
abstract:BACKGROUND:Zika virus (ZIKV) is an emergent threat provoking a worldwide explosive outbreak. Since January 2015, 41 countries reported autochthonous cases. In Brazil, an increase in Guillain-Barré syndrome and microcephaly cases was linked to ZIKV infections. A recent report describing low experimental transmission eff...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004816
更新日期:2016-06-24 00:00:00
abstract::In resource-limited settings, the scarcity of skilled personnel and adequate laboratory facilities makes the differential diagnosis of fevers complex [1-5]. Febrile illnesses are diagnosed clinically in most rural centers, and both Rapid Diagnostic Tests (RDTs) and clinical algorithms can be valuable aids to health wo...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004749
更新日期:2016-11-03 00:00:00
abstract::The major arboviral diseases in mainland China include Japanese encephalitis, dengue fever, Crimean-Congo hemorrhagic fever (also known as Xinjiang hemorrhagic fever), and tick-borne encephalitis. These and other newly found arbovirus infections due to Banna virus and Tahyna virus contribute to a large and relatively ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,评审
doi:10.1371/journal.pntd.0000624
更新日期:2010-04-27 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::The enteric protozoa Entamoeba histolytica is the causative agent of amebiasis, which is one of the most common parasitic diseases in developed and developing countries. Entamoeba nuttalli is the genetically closest species to E. histolytica in current phylogenetic analyses of Entamoeba species, and is prevalent in wi...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007923
更新日期:2019-12-05 00:00:00