Abstract:
BACKGROUND:Population suppression through mass-release of Aedes aegypti males carrying dominant-lethal transgenes has been demonstrated in the field. Where population dynamics show negative density-dependence, suppression can be enhanced if lethality occurs after the density-dependent (i.e. larval) stage. Existing molecular tools have limited current examples of such Genetic Pest Management (GPM) systems to achieving this through engineering 'cell-autonomous effectors' i.e. where the expressed deleterious protein is restricted to the cells in which it is expressed-usually under the control of the regulatory elements (e.g. promoter regions) used to build the system. This limits the flexibility of these technologies as regulatory regions with useful spatial, temporal or sex-specific expression patterns may only be employed if the cells they direct expression in are simultaneously sensitive to existing effectors, and also precludes the targeting of extracellular regions such as cell-surface receptors. Expanding the toolset to 'non-cell autonomous' effectors would significantly reduce these limitations. METHODOLOGY/PRINCIPAL FINDINGS:We sought to engineer female-specific, late-acting lethality through employing the Ae. aegypti VitellogeninA1 promoter to drive blood-meal-inducible, fat-body specific expression of tTAV. Initial attempts using pro-apoptotic effectors gave no evident phenotype, potentially due to the lower sensitivity of terminally-differentiated fat-body cells to programmed-death signals. Subsequently, we dissociated the temporal and spatial expression of this system by engineering a novel synthetic effector (Scorpion neurotoxin-TetO-gp67.AaHIT) designed to be secreted out of the tissue in which it was expressed (fat-body) and then affect cells elsewhere (neuro-muscular junctions). This resulted in a striking, temporary-paralysis phenotype after blood-feeding. CONCLUSIONS/SIGNIFICANCE:These results are significant in demonstrating for the first time an engineered 'action at a distance' phenotype in a non-model pest insect. The potential to dissociate temporal and spatial expression patterns of useful endogenous regulatory elements will extend to a variety of other pest insects and effectors.
journal_name
PLoS Negl Trop Disjournal_title
PLoS neglected tropical diseasesauthors
Haghighat-Khah RE,Harvey-Samuel T,Basu S,StJohn O,Scaife S,Verkuijl S,Lovett E,Alphey Ldoi
10.1371/journal.pntd.0007579subject
Has Abstractpub_date
2019-09-03 00:00:00pages
e0007579issue
9eissn
1935-2727issn
1935-2735pii
PNTD-D-18-01649journal_volume
13pub_type
杂志文章abstract:BACKGROUND:Transmission of Yersinia pestis by flea bite can occur by two mechanisms. After taking a blood meal from a bacteremic mammal, fleas have the potential to transmit the very next time they feed. This early-phase transmission resembles mechanical transmission in some respects, but the mechanism is unknown. Ther...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005276
更新日期:2017-01-12 00:00:00
abstract::Although several studies have associated Mycobacterium ulcerans (MU) infection, Buruli ulcer (BU), with slow moving water bodies, there is still no definite mode of transmission. Ecological and transmission studies suggest Variable Number Tandem Repeat (VNTR) typing as a useful tool to differentiate MU strains from ot...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003437
更新日期:2015-01-22 00:00:00
abstract:BACKGROUND:Schistosomiasis japonica is a zoonotic parasitic disease. After nearly 70 years of control efforts in China, Schistosomiasis transmission has been reduced to a much lower level. The absence or near absence of infections in humans or livestock, based on traditional fecal and serological tests, has made the ta...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,meta分析
doi:10.1371/journal.pntd.0007475
更新日期:2019-06-07 00:00:00
abstract::We evaluated the protection conferred by a first documented visit for clinical care of typhoid fever against recurrent typhoid fever prompting a visit. This study takes advantage of multi-year follow-up of a population with endemic typhoid participating in a cluster-randomized control trial of Vi capsular polysacchari...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,随机对照试验
doi:10.1371/journal.pntd.0008530
更新日期:2020-08-17 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:Cryptosporidium is a leading cause of moderate-to-severe diarrhea (MSD) in young children in Africa. We examined factors associated with Cryptosporidium infection in MSD cases enrolled at the rural western Kenya Global Enteric Multicenter Study (GEMS) site from 2008-2012. METHODOLOGY/PRINCIPAL FINDINGS:At h...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,多中心研究
doi:10.1371/journal.pntd.0006640
更新日期:2018-07-12 00:00:00
abstract::Japanese encephalitis virus (JEV) is a mosquito-borne, zoonotic flavivirus causing encephalitis in humans and reproductive disorder in pigs. JEV is present in large parts of Asia, where urbanization is high. Households within and outside Can Tho city, South Vietnam, were selected to monitor circulation of JEV. A neste...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002153
更新日期:2013-04-04 00:00:00
abstract:BACKGROUND:The global burden of cholera is largely unknown because the majority of cases are not reported. The low reporting can be attributed to limited capacity of epidemiological surveillance and laboratories, as well as social, political, and economic disincentives for reporting. We previously estimated 2.8 million...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003832
更新日期:2015-06-04 00:00:00
abstract:BACKGROUND:A Global Programme to Eliminate Lymphatic Filariasis was launched in 2000, with mass drug administration (MDA) as the core strategy of the programme. After completing 13 years of operations through 2012 and with MDA in place in 55 of 73 endemic countries, the impact of the MDA programme on microfilaraemia, h...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003319
更新日期:2014-11-20 00:00:00
abstract:BACKGROUND:Lymphatic filariasis (LF) is targeted for elimination in Sierra Leone. Epidemiological coverage of mass drug administration (MDA) with ivermectin and albendazole had been reported >65% in all 12 districts annually. Eight districts qualified to implement transmission assessment survey (TAS) in 2013 but were d...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008877
更新日期:2020-12-28 00:00:00
abstract:BACKGROUND:There are no published reports on studies comparing itraconazole (ITC), sulfamethoxazole-trimethoprim (cotrimoxazole, CMX), and ITC followed by CMX (ITC/CMX) in the treatment of paracoccidiodomycosis. This study aimed to compare the efficacy, effectiveness, safety and time to clinical and serologic cure in p...
journal_title:PLoS neglected tropical diseases
pub_type: 临床试验,杂志文章
doi:10.1371/journal.pntd.0002793
更新日期:2014-04-17 00:00:00
abstract::Global distribution patterns of Cladophialophora carrionii, agent of human chromoblastomycosis in arid climates of Africa, Asia, Australia, Central-and South-America, were compared with similar data of the vicarious Fonsecaea spp., agents of the disease in tropical rain forests. Population diversities among 73 C. carr...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004004
更新日期:2015-10-23 00:00:00
abstract::Cutaneous leishmaniasis caused by Leishmania major is an emergent, uncontrolled public health problem and there is no vaccine. A promising prophylactic approach has been immunotherapy with Toll-like receptor (TLR) agonists to enhance parasite-specific immune responses. We have previously reported that vaccination of C...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003546
更新日期:2015-03-04 00:00:00
abstract:BACKGROUND:Sri Lankan Russell's viper (Daboia russelii) envenoming is reported to cause myotoxicity and neurotoxicity, which are different to the effects of envenoming by most other populations of Russell's vipers. This study aimed to investigate evidence of myotoxicity in Russell's viper envenoming, response to antive...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005172
更新日期:2016-12-02 00:00:00
abstract::Chikungunya virus (CHIKV) is the only causative agent of CHIKV fever with persistent arthralgia, and in some cases may lead to neurological complications which can be highly fatal, therefore it poses severe health issues in many parts of the world. CHIKV transmission can be mediated via the Aedes albopictus mosquito; ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003544
更新日期:2015-03-04 00:00:00
abstract:BACKGROUND:Dengue is a growing problem both in its geographical spread and in its intensity, and yet current global distribution remains highly uncertain. Challenges in diagnosis and diagnostic methods as well as highly variable national health systems mean no single data source can reliably estimate the distribution o...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001760
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Marburg virus (MARV), a zoonotic pathogen causing severe hemorrhagic fever in man, has emerged in Angola resulting in the largest outbreak of Marburg hemorrhagic fever (MHF) with the highest case fatality rate to date. METHODOLOGY/PRINCIPAL FINDINGS:A mobile laboratory unit (MLU) was deployed as part of the...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001183
更新日期:2011-05-01 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:BACKGROUND:Zika virus (ZIKV) is an important flavivirus infection. Although ZIKV infection is rarely fatal, risk for severe disease in adults is not well described. Our objective was to describe the spectrum of illness in U.S. Veterans with ZIKV infection. METHODOLOGY:Case series study including patients with laborato...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006416
更新日期:2018-05-24 00:00:00
abstract::The circulation of vector-borne zoonotic viruses is largely determined by the overlap in the geographical distributions of virus-competent vectors and reservoir hosts. What is less clear are the factors influencing the distribution of virus-specific lineages. Japanese encephalitis virus (JEV) is the most important eti...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002411
更新日期:2013-08-29 00:00:00
abstract::Humoral immunity plays an important role in controlling dengue virus (DENV) infection. Antibodies (Abs) developed during primary infection protect against subsequent infection with the same dengue serotype, but can enhance disease following secondary infection with a heterologous serotype. A DENV virion has two surfac...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003564
更新日期:2015-03-11 00:00:00
abstract::The East/Central/South African genotype of Chikungunya virus with the E1-A226V mutation emerged in 2011 in Cambodia and spread in 2012. An outbreak of 190 cases was documented in Trapeang Roka, a rural village. We surveyed 425 village residents within 3-4 weeks after the outbreak, and determined the sensitivity and sp...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004281
更新日期:2016-01-11 00:00:00
abstract:BACKGROUND:Deposition of complement factors on Mycobacterium leprae may enhance phagocytosis. Such deposition may occur through the lectin pathway of complement. Three proteins of the lectin pathway are produced from the gene MASP1: Mannan-binding lectin-associated serine protease 1 (MASP-1) and MASP-3 and mannan-bindi...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007534
更新日期:2020-04-02 00:00:00
abstract:BACKGROUND:Mycobacterium tuberculosis causes the majority of tuberculosis (TB) cases in humans; however, in developing countries, human TB caused by M. bovis may be frequent but undetected. Human TB caused by M. bovis is considered a zoonosis; transmission is mainly through consumption of unpasteurized dairy products, ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004124
更新日期:2015-09-30 00:00:00
abstract:BACKGROUND:New strategies for collecting post-mortem tissue are necessary, particularly in areas with emerging infections. Minimally invasive autopsy (MIA) has been proposed as an alternative to conventional autopsy (CA), with promising results. Previous studies using MIA addressed the cause of death in adults and chil...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007625
更新日期:2019-07-22 00:00:00
abstract:BACKGROUND:Viral hemorrhagic fevers (VHF) are acute diseases associated with bleeding, organ failure, and shock. VHF may hardly be distinguished clinically from other diseases in the African hospital, including viral hepatitis. This study was conducted to determine if VHF and viral hepatitis contribute to hospital morb...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002435
更新日期:2013-09-19 00:00:00
abstract::Vaccines against Salmonella Typhi, the causative agent of typhoid fever, are commonly used by travellers, however, there are few examples of national immunization programs in endemic areas. There is therefore a paucity of data on the impact of typhoid immunization programs on localised populations of S. Typhi. Here we...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005274
更新日期:2017-01-06 00:00:00
abstract::Kinetoplastids are a group of parasites that includes several medically-important species. These human-infective species are transmitted by insect vectors in which the parasites undergo specific developmental transformations. For each species, this includes a stage in which parasites adhere to insect tissue via a hemi...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007570
更新日期:2019-07-29 00:00:00
abstract:BACKGROUND:Phlebotomus tobbi is a vector of Leishmania infantum, and P. sergenti is a vector of Leishmania tropica. Le. infantum and Le. tropica typically cause visceral or cutaneous leishmaniasis, respectively, but Le. infantum strains transmitted by P. tobbi can cause cutaneous disease. To better understand the compo...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001660
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Human lice, Pediculus humanus, are obligate blood-sucking parasites. Body lice, Pediculus h. humanus, occur in two divergent mitochondrial clades (A and D) each exhibiting a particular geographic distribution. Currently, the body louse is recognized as the only vector for louse-borne diseases. In this study,...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006397
更新日期:2018-04-17 00:00:00