Abstract:
BACKGROUND:Chagas disease is a neglected parasitic infection caused by the protozoan Trypanosoma cruzi (T. cruzi) that affects more than 6 million people, mainly in Latin America. Benznidazole is still the drug of choice in many countries to treat it in spite of its dosage regimen and adverse side effects such as such as allergic dermatitis, peripheral neuropathy and anorexia. Thus, novel, safer, and more efficacious treatments for such neglected infection are urgently required. METHODOLOGY:In this study, the efficacy of orally administered low doses of benznidazole (BNZ) nanoparticles was evaluated during the acute phase in mice infected with T. cruzi Nicaragua (TcN) that were immunosuppressed during the chronic stage of the disease. Moreover, the production of T. cruzi-specific antibodies, cardiac tissue inflammation and reactive oxygen species generation by Vero cells treated with both BNZ nanoparticles (BNZ-nps) and raw BNZ (R-BNZ) were also evaluated. PRINCIPAL FINDINGS:T. cruzi infected mice treated with 10, 25 or 50 mg/kg/day of BNZ-nps survived until euthanasia (92 days post infection (dpi)), while only 15% of infected untreated mice survived until the end of the experiment. PCR analysis of blood samples taken after induction of immunosuppression showed that a dosage of 25 mg/kg/day rendered 40% of the mice PCR-negative. The histological analysis of heart tissue showed a significant decrease in inflammation after treatments with 25 and 50 mg/kg/day, while a similar inflammatory damage was observed in both infected mice treated with R-BNZ (50 mg/kg/day) and untreated mice. In addition, only BNZ-nps treated mice led to lower levels of T. cruzi-specific antibodies to 50-100%. Finally, mammalian Vero cells treated with BNZ-nps or R-BNZ lead to a significant increase in ROS production. CONCLUSIONS:Based on these findings, this research highlights the in-vitro/in-vivo efficacy of nanoformulated BNZ against T. cruzi acute infections in immunosuppressed and non-immunosuppressed mice and provides further evidence for the optimization of dosage regimens to treat Chagas disease.
journal_name
PLoS Negl Trop Disjournal_title
PLoS neglected tropical diseasesauthors
Rial MS,Scalise ML,Arrúa EC,Esteva MI,Salomon CJ,Fichera LEdoi
10.1371/journal.pntd.0006119subject
Has Abstractpub_date
2017-12-21 00:00:00pages
e0006119issue
12eissn
1935-2727issn
1935-2735pii
PNTD-D-17-01063journal_volume
11pub_type
杂志文章abstract:BACKGROUND:Ofloxacin is a fluoroquinolone (FQ) used for the treatment of leprosy. FQs are known to interact with both A and B subunits of DNA gyrase and inhibit supercoiling activity of this enzyme. Mutations conferring FQ resistance have been reported to be found only in the gene encoding A subunit of this enzyme (gyr...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001838
更新日期:2012-01-01 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::The new world arenavirus Junín virus (JUNV) is the causative agent of Argentine hemorrhagic fever, a lethal human infectious disease. Adult laboratory mice are generally resistant to peripheral infection by JUNV. The mechanism underlying the mouse resistance to JUNV infection is largely unknown. We have reported that ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002933
更新日期:2014-06-05 00:00:00
abstract::Snakebites are a major Collective Health problem worldwide. In Brazil, Bothrops jararaca snake venom (BjV) evokes hemostatic disturbances, bleeding manifestations, and redox status imbalance. Specific antivenom therapy, although efficacious to revert most snakebite-induced manifestations, is incapable of treating seco...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006774
更新日期:2018-10-11 00:00:00
abstract:BACKGROUND:In mass vaccination campaigns, large volumes of data must be managed efficiently and accurately. In a reactive oral cholera vaccination (OCV) campaign in rural Haiti during an ongoing epidemic, we used a mobile health (mHealth) system to manage data on 50,000 participants in two isolated communities. METHOD...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003050
更新日期:2014-07-31 00:00:00
abstract:BACKGROUND:Mass anthelmintic drug administration is recommended in developing countries to address infection by soil-transmitted helminthiases (STH). We quantified the public health benefit of treatment with mebendazole in eight million Vietnamese children aged 5-14 years from 2006 to 2011. This was compared to the env...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006954
更新日期:2018-11-12 00:00:00
abstract:INTRODUCTION:Little is known about hepatotoxicity in patients with schistosome and HIV co-infections. Several studies have reported increased liver enzymes and bilirubin levels associated with schistosome infection. We investigated whether HIV-infected adults on antiretroviral therapy who had S. mansoni co-infection ha...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005867
更新日期:2017-08-17 00:00:00
abstract:BACKGROUND:Trypanosoma cruzi is a protozoan pathogen responsible for Chagas disease. Current therapies are inadequate because of their severe host toxicity and numerous side effects. The identification of new biotargets is essential for the development of more efficient therapeutic alternatives. Inhibition of sirtuins ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003725
更新日期:2015-04-15 00:00:00
abstract::Aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (DENV) types 1-4. Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004941
更新日期:2016-09-15 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pntd.0007025.]. ...
journal_title:PLoS neglected tropical diseases
pub_type: 已发布勘误
doi:10.1371/journal.pntd.0008725
更新日期:2020-09-01 00:00:00
abstract::The genus Onchocerca encompasses parasitic nematodes including Onchocerca volvulus, causative agent of river blindness in humans, and the zoonotic Onchocerca lupi infecting dogs and cats. In dogs, O. lupi adult worms cause ocular lesions of various degrees while humans may bear the brunt of zoonotic onchocercosis with...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006218
更新日期:2018-01-29 00:00:00
abstract:BACKGROUND:The soil-dwelling saprophyte bacterium Burkholderia pseudomallei is the cause of melioidosis, a severe disease of humans and animals in southeast Asia and northern Australia. Despite the detection of B. pseudomallei in various soil and water samples from endemic areas, the environmental habitat of B. pseudom...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0000364
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Leishmania development in the sand fly gut leads to highly infective forms called metacyclic promastigotes. This process can be routinely mimicked in culture. Gene expression-profiling studies by transcriptome analysis have been performed with the aim of studying promastigote forms in the sand fly gut, as we...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,评审
doi:10.1371/journal.pntd.0007288
更新日期:2019-05-09 00:00:00
abstract:BACKGROUND:Carrion' disease, caused by Bartonella bacilliformis, remains truly neglected due to its focal geographical nature. A wide spectrum of clinical manifestations, including asymptomatic bacteremia, and lack of a sensitive diagnostic test can potentially lead to a spread of the disease into non-endemic regions w...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003342
更新日期:2014-12-18 00:00:00
abstract::During the recent Ebola outbreak in West Africa several international mobile laboratories were deployed to the mainly affected countries Guinea, Sierra Leone and Liberia to provide ebolavirus diagnostic capacity. Additionally, imported cases and small outbreaks in other countries required global preparedness for Ebola...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,多中心研究
doi:10.1371/journal.pntd.0005570
更新日期:2017-05-01 00:00:00
abstract::Louse-borne relapsing fever (LBRF) borreliosis is caused by Borrelia recurrentis, and it is a deadly although treatable disease that is endemic in the Horn of Africa but has epidemic potential. Research on LBRF has been severely hampered because successful infection with B. recurrentis has been achieved only in primat...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0000522
更新日期:2009-09-29 00:00:00
abstract:BACKGROUND:Paracoccidioidomycosis, a primary fungal infection restricted to Latin America, is acquired by inhalation of fungal particles. The immunoregulatory mechanisms that control the severe and mild forms of paracoccidioidomycosis are still unclear. Indoleamine 2,3-dioxygenase (IDO), an IFN-γ induced enzyme that ca...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003330
更新日期:2014-11-20 00:00:00
abstract:BACKGROUND:Mycobacterium ulcerans (MU) is responsible for disfiguring skin lesions and is endemic on the Bellarine peninsula of southeastern Australia. Antibiotics have been shown to be highly effective in sterilizing lesions and preventing disease recurrences when used alone or in combination with surgery. Our practic...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002315
更新日期:2013-07-18 00:00:00
abstract:BACKGROUND:The high rate of leprosy cases among children under 15 years of age in Brazil indicates ongoing transmission within the community. The identification of the new leprosy cases among contacts can help identify the source of infection and interrupt the transmission chain. This study aims to determine the detect...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006261
更新日期:2018-02-26 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
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::Soil-transmitted helminthiases (STHs) constitute a public health problem that requires immediate action to resolve the morbidity of those harboring the parasites in their guts, to prevent infection in all those at risk, and to interrupt the vicious circle of poverty and disease in the affected communities, structural ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006672
更新日期:2018-09-13 00:00:00
abstract:INTRODUCTION:Individuals exposed to malaria infections for a long time develop immune responses capable of blocking Plasmodium transmission to mosquito vectors, potentially limiting parasite spreading in nature. Development of a malaria TB vaccine requires a better understanding of the mechanisms and main effectors res...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004807
更新日期:2016-06-29 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::Trypanosoma cruzi has been subdivided into seven Discrete Typing Units (DTUs), TcI-TcVI and Tcbat. Two major evolutionary models have been proposed to explain the origin of hybrid lineages, but while it is widely accepted that TcV and TcVI are the result of genetic exchange between TcII and TcIII strains, the origin o...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006139
更新日期:2017-12-18 00:00:00
abstract:BACKGROUND:The parasite Onchocerca volvulus has, until recently, been regarded as the cause of a chronic yet non-fatal condition. Recent analyses, however, have indicated that in addition to blindness, the parasite can also be directly associated with human mortality. Such analyses also suggested that the relationship ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001578
更新日期:2012-01-01 00:00:00
abstract::Q fever is a widespread zoonosis that is caused by Coxiella burnetii (C. burnetii), and ruminants are identified as the main sources of human infections. Some human cases have been described, but very limited information was available about Q fever in ruminants on Reunion Island, a tropical island in the Indian Ocean....
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003055
更新日期:2014-08-07 00:00:00
abstract:BACKGROUND:Dog rabies annually causes 24,000-70,000 deaths globally. We built a spreadsheet tool, RabiesEcon, to aid public health officials to estimate the cost-effectiveness of dog rabies vaccination programs in East Africa. METHODS:RabiesEcon uses a mathematical model of dog-dog and dog-human rabies transmission to...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006490
更新日期:2018-05-23 00:00:00
abstract:BACKGROUND:Many small studies have been done in Honduras estimating soil-transmitted helminthiasis (STH) prevalence but a country-wide study was last done in 2005. The country has the highest burden of malaria among all Central American countries. The present study was done to estimate country-wide STH prevalence and i...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003248
更新日期:2014-10-16 00:00:00
abstract::In Tunisia, cases of zoonotic cutaneous leishmaniasis caused by Leishmania major are increasing and spreading from the south-west to new areas in the center. To improve the current knowledge on L. major evolution and population dynamics, we performed multi-locus microsatellite typing of human isolates from Tunisian go...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004017
更新日期:2015-08-24 00:00:00