Abstract:
BACKGROUND:Current chemotherapy for Chagas disease is unsatisfactory due to its limited efficacy, particularly in the chronic phase, with frequent side effects that can lead to treatment discontinuation. Combined therapy is envisioned as an ideal approach since it may improve treatment efficacy whilst decreasing toxicity and the likelihood of resistance development. We evaluated the efficacy of posaconazole in combination with benznidazole on Trypanosoma cruzi infection in vivo. METHODS AND FINDINGS:Benznidazole and posaconazole were administered individually or in combination in an experimental acute murine infection model. Using a rapid treatment protocol for 7 days, the combined treatments were more efficacious in reducing parasitemia levels than the drugs given alone, with the effects most evident in combinations of sub-optimal doses of the drugs. Subsequently, the curative action of these drug combinations was investigated, using the same infection model and 25, 50, 75 or 100 mg/kg/day (mpk) of benznidazole in combination with 5, 10 or 20 mpk of posaconazole, given alone or concomitantly for 20 days. The effects of the combination treatments on parasitological cures were higher than the sum of such effects when the drugs were administered separately at the same doses, indicating synergistic activity. Finally, sequential therapy experiments were carried out with benznidazole or posaconazole over a short interval (10 days), followed by the second drug administered for the same period of time. It was found that the sequence of benznidazole (100 mpk) followed by posaconazole (20 mpk) provided cure rates comparable to those obtained with the full (20 days) treatments with either drug alone, and no cure was observed for the short treatments with drugs given alone. CONCLUSIONS:Our data demonstrate the importance of investigating the potential beneficial effects of combination treatments with marketed compounds, and showed that combinations of benznidazole with posaconazole have a positive interaction in murine models of Chagas disease.
journal_name
PLoS Negl Trop Disjournal_title
PLoS neglected tropical diseasesauthors
Diniz Lde F,Urbina JA,de Andrade IM,Mazzeti AL,Martins TA,Caldas IS,Talvani A,Ribeiro I,Bahia MTdoi
10.1371/journal.pntd.0002367subject
Has Abstractpub_date
2013-08-15 00:00:00pages
e2367issue
8eissn
1935-2727issn
1935-2735pii
PNTD-D-13-00222journal_volume
7pub_type
杂志文章abstract::In this communication, a case of black grain eumycetoma produced by the fungus C. atrobrunneum is reported. The patient was initially misdiagnosed with M. mycetomatis eumycetoma based on the grains' morphological and cytological features. However, further aerobic culture of the black grains generated a melanised fungu...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007276
更新日期:2019-05-30 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:INTRODUCTION:A high proportion of grade 2 disability (visible deformity) is indicative of delay in detection of leprosy and leprosy is one of the major causes of preventable disability. We conducted this study to determine the risk factors associated with disability (G2D and G1D) among adult new leprosy cases and to me...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,多中心研究
doi:10.1371/journal.pntd.0007495
更新日期:2019-06-27 00:00:00
abstract:BACKGROUND:Taenia solium cysticercosis affects millions of impoverished people worldwide and can cause neurocysticercosis, an infection of the central nervous system which is potentially fatal. Children may represent an especially vulnerable population to neurocysticercosis, due to the risk of cognitive impairment duri...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006465
更新日期:2018-05-08 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::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:INTRODUCTION:This paper discusses the presence of Aedes aegypti pupae in different types of containers considering: volume, pH of the container, among other variables. METHODS:A nonlinear method for selection was applied, based on Mutual Information, by placing in order of importance the most appropriate variables for...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006592
更新日期:2018-07-23 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:BACKGROUND:Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropri...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005527
更新日期:2017-05-12 00:00:00
abstract:BACKGROUND:Public health responses to outbreaks of dengue, chikungunya, and Zika virus have been stymied by the inability to control the primary vector, Aedes aegypti mosquitos. Consequently, the need for novel approaches to Aedes vector control is urgent. Placement of three autocidal gravid ovitraps (AGO traps) in ~85...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007538
更新日期:2019-07-25 00:00:00
abstract:BACKGROUND:Anti-leishmanial drug regimens that include a single dose AmBisome could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL) but the appropriate single dose is unknown. METHODOLOGY:A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive des...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1371/journal.pntd.0002613
更新日期:2014-01-16 00:00:00
abstract:BACKGROUND:Praziquantel-based mass treatment is the main approach to controlling schistosomiasis mansoni in endemic areas. Interventions such as provision and use of safe water, minimising contact with infested water, disposal of stool in latrines and snail control provide key avenues to break the transmission cycle an...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005982
更新日期:2017-10-02 00:00:00
abstract::Dengue fever, a mosquito-borne viral disease in humans, has been endemic in many Southeast Asian countries. Since its first outbreak in 1978 in Foshan, Guangdong province, China, dengue has been continually epidemic in recent years in Guangdong, which raised the concern whether dengue infection is endemic in Guangdong...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008049
更新日期:2020-03-03 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::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
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:BACKGROUND:Dengue is the most important mosquito-borne viral infection to affect humans. Although it usually manifests as a self-limited febrile illness, complications may occur as the fever subsides. A systemic vascular leak syndrome that sometimes progresses to life-threatening hypovolaemic shock is the most serious ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005498
更新日期:2017-04-27 00:00:00
abstract:BACKGROUND:Contacts of leprosy patients are at increased risk of developing leprosy and need to be targeted for early diagnosis. Seropositivity to the phenolic glycolipid I (PGL-I) antigen of Mycobacterium leprae has been used to identify contacts who have an increased risk of developing leprosy. In the present study, ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001711
更新日期:2012-01-01 00:00:00
abstract::Control of arbovirus transmission remains focused on vector control through application of insecticides directly to the environment. However, these insecticide applications are often reactive interventions that can be poorly-targeted, inadequate for localized control during outbreaks, and opposed due to environmental ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007210
更新日期:2019-03-07 00:00:00
abstract:BACKGROUND:Dog-bites and rabies are under-reported in developing countries such as Pakistan and there is a poor understanding of the disease burden. We prospectively collected data utilizing mobile phones for dog-bite and rabies surveillance across nine emergency rooms (ER) in Pakistan, recording patient health-seeking...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002574
更新日期:2013-12-12 00:00:00
abstract::Cysticercosis is caused by Taenia solium, a parasitic disease that affects humans and rurally bred pigs in developing countries. The cysticercus may localize in the central nervous system of the human, causing neurocysticercosis, the most severe and frequent form of the disease. There appears to be an association betw...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0000284
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:In the past decade, research on neglected tropical diseases (NTDs) has intensified in response to the need to enhance community participation in health delivery, establish monitoring and surveillance systems, and integrate existing disease-specific treatment programs to control overlapping NTD burdens and de...
journal_title:PLoS neglected tropical diseases
pub_type: 历史文章,杂志文章
doi:10.1371/journal.pntd.0003939
更新日期:2015-08-04 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:Treatment needs for Schistosoma haematobium are commonly evaluated using urine filtration with detection of parasite eggs under a microscope. A common symptom of S. haematobium is hematuria, the passing of blood in urine. Hence, the use of hematuria-based diagnostic techniques as a proxy for the assessment o...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008451
更新日期:2020-08-20 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pntd.0008129.]. ...
journal_title:PLoS neglected tropical diseases
pub_type: 已发布勘误
doi:10.1371/journal.pntd.0008721
更新日期:2020-09-01 00:00:00
abstract::We recently reported the medicinal chemistry re-optimization of a series of compounds derived from the human tyrosine kinase inhibitor, lapatinib, for activity against Plasmodium falciparum. From this same library of compounds, we now report potent compounds against Trypanosoma brucei brucei (which causes human Africa...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006834
更新日期:2018-11-26 00:00:00
abstract:OBJECTIVES:To assess if a probabilistic model could be used to estimate the combined prevalence of infection with any species of intestinal nematode worm when only the separate prevalence of each species is reported, and to estimate the extent to which simply taking the highest individual species prevalence underestima...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0000655
更新日期:2010-04-13 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::Animal African Trypanosomosis (AAT) presents a severe problem for agricultural development in sub-Saharan Africa. It is caused by several trypanosome species and current means of diagnosis are expensive and impractical for field use. Our aim was to discover antigens for the detection of antibodies to Trypanosoma congo...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002936
更新日期:2014-06-12 00:00:00
abstract:INTRODUCTION:Between 1998 and 2010, S. Typhi was an uncommon cause of bloodstream infection (BSI) in Blantyre, Malawi and it was usually susceptible to first-line antimicrobial therapy. In 2011 an increase in a multidrug resistant (MDR) strain was detected through routine bacteriological surveillance conducted at Queen...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003748
更新日期:2015-04-24 00:00:00