| determination of the prevalence of african trypanosome species in indigenous dogs of mambwe district, eastern zambia, by loop-mediated isothermal amplification. | dogs have been implicated to serve as links for parasite exchange between livestock and humans and remain an important source of emerging and re-emerging diseases including trypanosome infections. yet, canine african trypanosomosis (cat), particularly in indigenous dogs (mongrel breed) remains under- reported in literature. this study evaluated the performance of loop-mediated isothermal amplification (lamp) in detecting trypanosomes in blood from indigenous dogs of tsetse-infested mambwe distri ... | 2014 | 24411022 |
| activity of diimidazoline amides against african trypanosomiasis. | we identified several diimidazoline mono- and diamides that were as potent as pentamidine against trypanosoma brucei rhodesiense in vitro. all of these were also less cytotoxic than pentamidine, but none was as effective as the latter in a t. brucei rhodesiense-infected mouse model. a single imidazoline may be sufficient for high antitrypanosomal activity provided that a second weak base functional group is present. | 2014 | 24398295 |
| antitrypanosomal isoflavan quinones from abrus precatorius. | human african trypanosomiasis is a neglected tropical disease in sub saharan africa that is fatal if left untreated. in a search for new natural products with antitrypanosomal activity, we recently identified abruquinones b and i from abrus precatorius as potent in vitro trypanocidal compounds with high selectivity indices. to obtain sufficient compound for in vivo efficacy tests in mice, a second batch of plant material was re-collected and extracted. however, the chemical profiles of the two b ... | 2014 | 24382449 |
| increased burden of cardiovascular disease in carriers of apol1 genetic variants. | two distinct alleles in the gene encoding apolipoprotein l1 (apol1), a major component of high-density lipoprotein, confer protection against trypanosoma brucei rhodesiense infection and also increase risk for chronic kidney disease. approximately 14% of americans with african ancestry carry 2 apol1 risk alleles, accounting for the high chronic kidney disease burden in this population. | 2014 | 24379297 |
| antitrypanosomal isothiocyanate and thiocarbamate glycosides from moringa peregrina. | o-methyl (1), o-ethyl (2), and o-butyl (3) 4-[(α-l-rhamnosyloxy) benzyl] thiocarbamate (e), along with 4-(α-l-rhamnosyloxy) benzyl isothiocyanate (4) have been isolated from the aerial parts of moringa peregrina. the compounds were tested for in vitro activity against trypanosoma brucei rhodesiense and cytotoxicity in rat skeletal myoblasts (l6 cells). the most potent compound was 4 with an ic50 of 0.10 µm against t.b. rhodesiense and a selectivity index of 73, while the thiocarbamate glycosides ... | 2014 | 24310210 |
| cattle movements and trypanosomes: restocking efforts and the spread of trypanosoma brucei rhodesiense sleeping sickness in post-conflict uganda. | the northwards spread of acute t. b. rhodesiense sleeping sickness in uganda has been linked to cattle movements associated with restocking following the end to military conflict in 2006. this study examined the number of cattle traded from t. b. rhodesiense endemic districts, the prevalence of the parasite in cattle being traded and the level of trypanocidal treatment at livestock markets. | 2013 | 24289452 |
| population genetics of trypanosoma brucei rhodesiense: clonality and diversity within and between foci. | african trypanosomes are unusual among pathogenic protozoa in that they can undergo their complete morphological life cycle in the tsetse fly vector with mating as a non-obligatory part of this development. trypanosoma brucei rhodesiense, which infects humans and livestock in east and southern africa, has classically been described as a host-range variant of the non-human infective trypanosoma brucei that occurs as stable clonal lineages. we have examined t. b. rhodesiense populations from east ... | 2013 | 24244771 |
| il-6 is upregulated in late-stage disease in monkeys experimentally infected with trypanosoma brucei rhodesiense. | the management of human african trypanosomiasis (hat) is constrained by lack of simple-to-use diagnostic, staging, and treatment tools. the search for novel biomarkers is, therefore, essential in the fight against hat. the current study aimed at investigating the potential of il-6 as an adjunct parameter for hat stage determination in vervet monkey model. four adult vervet monkeys (chlorocebus aethiops) were experimentally infected with trypanosoma brucei rhodesiense and treated subcuratively at ... | 2013 | 24194772 |
| in silico prediction and experimental evaluation of furanoheliangolide sesquiterpene lactones as potent agents against trypanosoma brucei rhodesiense. | as a continuation of our earlier study on the in vitro antiprotozoal activity of 40 natural sesquiterpene lactones (stls), we extended the set of tested compounds from our laboratories to 59. on the basis of this extended data set, further enriched by literature data for 10 compounds tested under the same conditions, our quantitative structure-activity relationship (qsar) analyses for activity against t. brucei rhodesiense (etiologic agent of human african trypanosomiasis, or sleeping sickness) ... | 2014 | 24165182 |
| the dispersal ecology of rhodesian sleeping sickness following its introduction to a new area. | tsetse-transmitted human and animal trypanosomiasis are constraints to both human and animal health in sub-saharan africa, and although these diseases have been known for over a century, there is little recent evidence demonstrating how the parasites circulate in natural hosts and ecosystems. the spread of rhodesian sleeping sickness (caused by trypanosoma brucei rhodesiense) within uganda over the past 15 years has been linked to the movement of infected, untreated livestock (the predominant re ... | 2013 | 24130913 |
| sleeping sickness in buikwe south health sub-district: neuroinfection situation report. | the aim of this paper is to describe the incidence of trypanosoma brucei rhodesiense sleeping sickness in the last functioning treatment centre in buikwe south hsd in southeast uganda, in mukono district, for a 19-year period (1989-2008). this is a report on the treatment outcome, structure of population affected, comparison with the published data on general incidence of t. b rhodesiensae in uganda and functioning of sleeping sickness control program. | 2013 | 24013601 |
| antitrypanosomal triterpenoid with an ε-lactone e-ring from salvia urmiensis. | a new triterpenoid, urmiensolide (1), was isolated from salvia urmiensis. the structure was elucidated by a combination of 1d and 2d nmr, hresims, and x-ray crystallographic analyses. the absolute configuration was established by comparison of experimental and simulated ecd spectra. urmiensolide is the first pentacyclic triterpenoid bearing a ε-lactone e-ring. the compound showed in vitro antitrypanosoal activity with an ic₅₀ value of 5.6 μm against the trypanosoma brucei rhodesiense stib 900 st ... | 2013 | 24007549 |
| whole-genome sequencing of trypanosoma brucei reveals introgression between subspecies that is associated with virulence. | human african trypanosomiasis is caused by two subspecies of trypanosoma brucei. trypanosoma brucei rhodesiense is found in east africa and frequently causes acute disease, while trypanosoma brucei gambiense is found in west africa and is associated with chronic disease. samples taken from a single focus of a ugandan outbreak of t. b. rhodesiense in the 1980s were associated with either chronic or acute disease. we sequenced the whole genomes of two of these isolates, which showed that they are ... | 2013 | 23963174 |
| identification of trypanosome proteins in plasma from african sleeping sickness patients infected with t. b. rhodesiense. | control of human african sleeping sickness, caused by subspecies of the protozoan parasite trypanosoma brucei, is based on preventing transmission by elimination of the tsetse vector and by active diagnostic screening and treatment of infected patients. to identify trypanosome proteins that have potential as biomarkers for detection and monitoring of african sleeping sickness, we have used a 'deep-mining" proteomics approach to identify trypanosome proteins in human plasma. abundant human plasma ... | 2013 | 23951171 |
| a current analysis of chemotherapy strategies for the treatment of human african trypanosomiasis. | despite the recent advances in drug research, finding a safe, effective, and easy to use chemotherapy for human african trypanosomiasis (hat) remains a challenging task. the four current anti-trypanosomiasis drugs have major disadvantages that limit more widespread use of these drugs in the endemic regions of sub-saharan africa. pentamidine and suramin are limited by their effectiveness against the only first stage of trypanosoma brucei gambiense and trypanosoma brucei rhodesiense, respectively. ... | 2013 | 23916333 |
| glossina fuscipes populations provide insights for human african trypanosomiasis transmission in uganda. | uganda has both forms of human african trypanosomiasis (hat): the chronic gambiense disease in the northwest and the acute rhodesiense disease in the south. the recent spread of rhodesiense into central uganda has raised concerns given the different control strategies the two diseases require. we present knowledge on the population genetics of the major vector species glossina fuscipes fuscipes in uganda with a focus on population structure, measures of gene flow between populations, and the occ ... | 2013 | 23845311 |
| human african trypanosomiasis. | human african trypanosomiasis or sleeping sickness is a neglected tropical disease that affects populations in sub-saharan africa. the disease is caused by infection with the gambiense and rhodesiense subspecies of the extracellular parasite trypanosoma brucei, and is transmitted to humans by bites of infected tsetse flies. the disease evolves in two stages, the hemolymphatic and meningoencephalitic stages, the latter being defined by central nervous system infection after trypanosomal traversal ... | 2013 | 23829907 |
| preliminary investigation of trypanosomosis in exotic dog breeds from zambia's luangwa and zambezi valleys using lamp. | abstract. canine african trypanosomosis (cat) is rarely reported in the literature. in this preliminary study, we evaluated the performance of loop-mediated isothermal amplification (lamp) against microscopy to detect cat in six exotic dog breeds naturally infected with trypanosomes from zambia's south luangwa national park and chiawa game management area. to our knowledge, this is the first report of cat in zambia. the patients exhibited a variety of aspecific clinical signs. the lamp did not o ... | 2013 | 23716412 |
| 2-arylpaullones are selective antitrypanosomal agents. | antileishmanial paullone-chalcone hybrid molecules display antiparasitic activity against trypanosoma brucei rhodesiense blood stream forms, albeit with low selectivity against human thp-1 cells. in order to develop less toxic analogues, paullones with acrylamide or aryl substituents in 2-position were synthesized, of which the latter exhibited potent antiparasitic activity with excellent selectivity profiles. the most potent compound identified in this study was 9-tert-butyl-2-(4-morpholinophen ... | 2013 | 23648975 |
| socio-economic and cultural determinants of human african trypanosomiasis at the kenya - uganda transboundary. | kenya and uganda have reported different human african trypanosomiasis incidences in the past more than three decades, with the latter recording more cases. this cross-sectional study assessed the demographic characteristics, tsetse and trypanosomiasis control practices, socio-economic and cultural risk factors influencing trypanosoma brucei rhodesiense (t.b.r.) infection in teso and busia districts, western kenya and tororo and busia districts, southeast uganda. a conceptual framework was postu ... | 2013 | 23638206 |
| new biomarkers for stage determination in trypanosoma brucei rhodesiense sleeping sickness patients. | accurate stage determination is crucial in the choice of treatment for patients suffering from sleeping sickness, also known as human african trypanosomiasis (hat). current staging methods, based on the counting of white blood cells (wbc) and the detection of parasites in the cerebrospinal fluid (csf) have limited accuracy. we hypothesized that immune mediators reliable for staging t. b. gambiense hat could also be used to stratify t. b. rhodesiense patients, the less common form of hat.a popula ... | 2013 | 23369533 |
| naphthoquinone derivatives exert their antitrypanosomal activity via a multi-target mechanism. | recently, we reported on a new class of naphthoquinone derivatives showing a promising anti-trypanosomatid profile in cell-based experiments. the lead of this series (b6, 2-phenoxy-1,4-naphthoquinone) showed an ed(50) of 80 nm against trypanosoma brucei rhodesiense, and a selectivity index of 74 with respect to mammalian cells. a multitarget profile for this compound is easily conceivable, because quinones, as natural products, serve plants as potent defense chemicals with an intrinsic multifunc ... | 2013 | 23350008 |
| the use of loop-mediated isothermal amplification (lamp) to detect the re-emerging human african trypanosomiasis (hat) in the luangwa and zambezi valleys. | loop-mediated isothermal amplification (lamp) is a novel strategy which amplifies dna with high sensitivity and rapidity under isothermal conditions. in the present study, the performance of the repetitive insertion mobile element (rime)-lamp and human serum resistance-associated gene (sra)-lamp assays were evaluated using clinical specimens obtained from four male patients from luangwa and zambezi valleys in zambia and zimbabwe, respectively. | 2012 | 23211002 |
| identification of compounds with anti-proliferative activity against trypanosoma brucei brucei strain 427 by a whole cell viability based hts campaign. | human african trypanosomiasis (hat) is caused by two trypanosome sub-species, trypanosoma brucei rhodesiense and trypanosoma brucei gambiense. drugs available for the treatment of hat have significant issues related to difficult administration regimes and limited efficacy across species and disease stages. hence, there is considerable need to find new alternative and less toxic drugs. an approach to identify starting points for new drug candidates is high throughput screening (hts) of large comp ... | 2012 | 23209849 |
| an exploratory gis-based method to identify and characterise landscapes with an elevated epidemiological risk of rhodesian human african trypanosomiasis. | specific land cover types and activities have been correlated with trypanosoma brucei rhodesiense distributions, indicating the importance of landscape for epidemiological risk. however, methods proposed to identify specific areas with elevated epidemiological risk (i.e. where transmission is more likely to occur) tend to be costly and time consuming. this paper proposes an exploratory spatial analysis using geo-referenced human african trypanosomiasis (hat) cases and matched controls from serer ... | 2012 | 23171150 |
| stage progression and neurological symptoms in trypanosoma brucei rhodesiense sleeping sickness: role of the cns inflammatory response. | human african trypanosomiasis progresses from an early (hemolymphatic) stage, through cns invasion to the late (meningoencephalitic) stage. in experimental infections disease progression is associated with neuroinflammatory responses and neurological symptoms, but this concept requires evaluation in african trypanosomiasis patients, where correct diagnosis of the disease stage is of critical therapeutic importance. | 2012 | 23145191 |
| trypanosome resistance to human innate immunity: targeting achilles' heel. | trypanosome lytic factors (tlfs) are powerful, naturally occurring toxins in humans that provide sterile protection against infection by several african trypanosomes. these trypanocidal complexes predominantly enter the parasite by binding to the trypanosome haptoglobin/hemoglobin receptor (hphbr), trafficking to the lysosome, causing membrane damage and, ultimately, cell lysis. despite tlf-mediated immunity, the parasites that cause human african trypanosomiasis (hat), trypanosoma brucei rhodes ... | 2012 | 23059119 |
| molecular epidemiological studies on animal trypanosomiases in ghana. | african trypanosomes are extracellular protozoan parasites that are transmitted between mammalian hosts by the bite of an infected tsetse fly. human african trypanosomiasis (hat) or sleeping sickness is caused by trypanosoma brucei rhodesiense or t. brucei gambiense, while african animal trypanosomiasis (aat) is caused mainly by t. vivax, t. congolense, t. simiae,t. evansi and t. brucei brucei. trypanosomiasis is of public health importance in humans and is also the major constraint for livestoc ... | 2012 | 23025330 |
| human african trypanosomiasis in a traveler: diagnostic pitfalls. | abstract. an israeli traveler returning from tanzania presented with a relapsing febrile illness. a diagnosis of trypanosoma brucei rhodesiense infection was established by blood smear after nearly a month. blood polymerase chain reaction failed to provide an early diagnosis of human african trypanososmiasis. recognition of suggestive signs should prompt physicians to perform repeated tests before ruling out human african trypanososmiasis. | 2012 | 22855756 |
| pharmacology of db844, an orally active aza analogue of pafuramidine, in a monkey model of second stage human african trypanosomiasis. | novel drugs to treat human african trypanosomiasis (hat) are still urgently needed despite the recent addition of nifurtimox-eflornithine combination therapy (nect) to who model lists of essential medicines against second stage hat, where parasites have invaded the central nervous system (cns). the pharmacology of a potential orally available lead compound, n-methoxy-6-{5-[4-(n-methoxyamidino) phenyl]-furan-2-yl}-nicotinamidine (db844), was evaluated in a vervet monkey model of second stage hat, ... | 2012 | 22848769 |
| cinnamoylphenethyl amides from polygonum hyrcanicum possess anti-trypanosomal activity. | a methanolic extract from aerial parts of polygonum hyrcanicum (polygonaceae) showed high activity against trypanosoma brucei rhodesiense (ic50 = 3.7 microg/ml). bioassay-guided fractionation of the extract resulted in isolation of cinnamoylphenethyl amides, including n-trans-caffeoyltyramine (1), n-trans-p-coumaroyltyramine (7), and n-trans-feruloyltyramine (8) as the main active constituents (ic50s ranging from 2.2 to 13.3 microm). some structurally related, but less active compounds, such as ... | 2012 | 22816300 |
| trypanosoma brucei gambiense group 1 is distinguished by a unique amino acid substitution in the hphb receptor implicated in human serum resistance. | trypanosoma brucei rhodesiense (tbr) and t. b. gambiense (tbg), causative agents of human african trypanosomiasis (sleeping sickness) in africa, have evolved alternative mechanisms of resisting the activity of trypanosome lytic factors (tlfs), components of innate immunity in human serum that protect against infection by other african trypanosomes. in tbr, lytic activity is suppressed by the tbr-specific serum-resistance associated (sra) protein. the mechanism in tbg is less well understood but ... | 2012 | 22802982 |
| discovery of nitroheterocycles active against african trypanosomes. in vitro screening and preliminary sar studies. | a selection of 76 nitroheterocycles and related compounds from our in-house compound library was screened in vitro against the parasite trypanosoma brucei rhodesiense, causative agent of human african trypanosomiasis (hat). the unspecific cytotoxicity of the compounds was also evaluated against rat myoblast l6-cells to measure the selectivity of the compounds towards the parasite. this screening revealed some preliminary structure-activity relationships (sar) among the series, and six hit compou ... | 2012 | 22738640 |
| priorities for the elimination of sleeping sickness. | sleeping sickness describes two diseases, both fatal if left untreated: (i) gambian sleeping sickness caused by trypanosoma brucei gambiense, a chronic disease with average infection lasting around 3 years, and (ii) rhodesian sleeping sickness caused by t. b. rhodesiense, an acute disease with death occurring within weeks of infection. control of gambian sleeping sickness is based on case detection and treatment involving serological screening, followed by diagnostic confirmation and staging. in ... | 2012 | 22726645 |
| an alternative form of melarsoprol in sleeping sickness. | human african trypanosomiasis (hat), or sleeping sickness, is a major threat to human health throughout sub-saharan africa. almost always fatal if untreated or inadequately treated, a commonly used drug for treating late-stage hat, and the only drug for late-stage trypanosoma brucei rhodesiense, is intravenous melarsoprol, which kills 5% of patients receiving it. melarsoprol cyclodextrin inclusion complexes have been tested in a highly reliable mouse model of hat. these complexes increase the or ... | 2012 | 22704910 |
| apol1 expression is induced by trypanosoma brucei gambiense infection but is not associated with differential susceptibility to sleeping sickness. | most african trypanosome species are sensitive to trypanolytic factors (tlfs) present in human serum. trypanosome lysis was demonstrated to be associated with apolipoprotein l-i (apol1). trypanosoma brucei (t. b.) gambiense and trypanosoma brucei rhodesiense, the two human infective trypanosome species, have both developed distinct resistance mechanisms to apol1 mediated lysis. whereas t. b. rhodesiense resistance is linked with the expression of the serum resistance associated (sra) protein tha ... | 2012 | 22691369 |
| modeling the control of trypanosomiasis using trypanocides or insecticide-treated livestock. | in uganda, rhodesian sleeping sickness, caused by trypanosoma brucei rhodesiense, and animal trypanosomiasis caused by t. vivax and t. congolense, are being controlled by treating cattle with trypanocides and/or insecticides. we used a mathematical model to identify treatment coverages required to break transmission when host populations consisted of various proportions of wild and domestic mammals, and reptiles. | 2012 | 22616017 |
| human african trypanosomiasis in a belgian traveller returning from the masai mara area, kenya, february 2012. | a belgian traveller was diagnosed with human african trypanosomiasis (hat) due to trypanosoma brucei rhodesiense nine days after visiting the masai mara area in kenya. he presented with an inoculation chancre and was treated with suramin within four days of fever onset. two weeks earlier, hat was also reported in a german traveller who had visited the masai mara area. because no cases have occurred in the area for over 12 years, this may indicate a focal cluster of hat. | 2012 | 22433595 |
| trypanosoma brucei rhodesiense infection in a german traveller returning from the masai mara area, kenya, january 2012. | in january 2012, a case of human african trypanosomiasis (hat) has been identified in germany in a traveller returning from the masai mara area in kenya. the 62-year-old man had travelled to the masai mara game park from 18 to 19 january 2012 and developed fever on 28 january. the infection with trypanosoma brucei rhodesiense was confirmed by laboratory testing three days hereafter. | 2012 | 22433594 |
| synthesis and structure-activity relationships of new quinolone-type molecules against trypanosoma brucei. | human african trypanosomiasis (hat) or sleeping sickness is caused by two subspecies of trypanosoma brucei , trypanosoma brucei gambiense , and trypanosoma brucei rhodesiense and is one of africa's old plagues. it causes a huge number of infections and cases of death per year because, apart from limited access to health services, only inefficient chemotherapy is available. since it was reported that quinolones such as ciprofloxacin show antitrypanosomal activity, a novel quinolone-type library w ... | 2012 | 22376072 |
| multiorgan dysfunction caused by travel-associated african trypanosomiasis. | we describe a case of multiorgan dysfunction secondary to trypanosoma brucei rhodesiense infection acquired on safari in zambia. this case was one of several recently reported to promed-mail in persons who had traveled to this region. trypanosomiasis remains rare in travelers but should be considered in febrile patients who have returned from trypanosomiasis-endemic areas of africa. | 2012 | 22305185 |
| genome-wide snp analysis reveals distinct origins of trypanosoma evansi and trypanosoma equiperdum. | trypanosomes cause a variety of diseases in man and domestic animals in africa, latin america and asia. in the trypanozoon subgenus, trypanosoma brucei gambiense and t. b. rhodesiense cause human african trypanosomiasis, while t. b. brucei, t. evansi and t. equiperdum are responsible for nagana, surra and dourine in domestic animals, respectively. the genetic relationships between t. evansi and t. equiperdum and other trypanozoon species remain unclear because the majority of phylogenetic analys ... | 2017 | 28541535 |
| lead selection of antiparasitic compounds from a focused library of benzenesulfonyl derivatives of heterocycles. | a library of 89 synthetic benzenesulfonyl derivatives of heterocycles with drug-like properties was assayed for in vitro antiparasitic activity and the results were added to our previously reported derivatives for a comprehensive sar evaluation. four compounds showed an ic50 between 0.25 and 3μm against leishmania donovani and low cytotoxicity. compound g{16} (1-(2,3,5,6-tetramethylphenylsulfonyl)-2-methylindoline), was particularly interesting with an ic50 similar to the reference drug miltefos ... | 2017 | 28789893 |
| bifurcatriol, a new antiprotozoal acyclic diterpene from the brown alga bifurcaria bifurcata. | linear diterpenes that are commonly found in brown algae are of high chemotaxonomic and ecological importance. this study reports bifurcatriol (1), a new linear diterpene featuring two stereogenic centers isolated from the irish brown alga bifurcariabifurcata. the gross structure of this new natural product was elucidated based on its spectroscopic data (ir, 1d and 2d-nmr, hrms). its absolute configuration was identified by experimental and computational vibrational circular dichroism (vcd) spec ... | 2017 | 28767061 |
| alkamides from anacyclus pyrethrum l. and their in vitro antiprotozoal activity. | in our ongoing study to evaluate the antiprotozoal activity of alkamides from asteraceae, a dichloromethane extract from the roots of anacycluspyrethrum l. showed a moderate in vitro activity against the nf54 strain of plasmodium falciparum and against leishmaniadonovani (amastigotes, mhom/et/67/l82 strain). seven pure alkamides and a mixture of two further alkamides were isolated by column chromatography followed by preparative high performance liquid chromatography. the alkamides were identifi ... | 2017 | 28498323 |
| antiparasitic sesquiterpenes from the cameroonian spice scleria striatinux and preliminary in vitro and in silico dmpk assessment. | the antiparasitic activity and preliminary in vitro and in silico drug metabolism and pharmacokinetic (dmpk) assessment of six isomeric sesquiterpenes (1-6), isolated from the cameroonian spice scleria striatinux de wild (cyperaceae) is reported. the study was prompted by the observation that two of the compounds (1 and 2) exhibited varying levels of antiparasitic activity on plasmodium falciparum, trypanosoma brucei rhodesiense, trypanosoma cruzi and leishmania donovani. the in silico method em ... | 2017 | 28421410 |
| anti-trypanosomatid elemanolide sesquiterpene lactones from vernonia lasiopus o. hoffm. | sleeping sickness or human african trypanosomiasis (hat) is a neglected tropical disease (ntd) threatening millions of peoples' lives with thousands infected. the disease is endemic in poorly developed regions of sub-saharan africa and is caused by the kinetoplastid "protozoan" parasite trypanosoma brucei. the parasites are transmitted to humans through bites of infected tsetse flies of the genus glossina. the few available drugs for treatment of this disease are highly toxic, difficult to admin ... | 2017 | 28397756 |
| development of novel peptide-based michael acceptors targeting rhodesain and falcipain-2 for the treatment of neglected tropical diseases (ntds). | this paper describes the development of a class of peptide-based inhibitors as novel antitrypanosomal and antimalarial agents. the inhibitors are based on a characteristic peptide sequence for the inhibition of the cysteine proteases rhodesain of trypanosoma brucei rhodesiense and falcipain-2 of plasmodium falciparum. we exploited the reactivity of novel unsaturated electrophilic functions such as vinyl-sulfones, -ketones, -esters, and -nitriles. the michael acceptors inhibited both rhodesain an ... | 2017 | 28763614 |
| antileukemic ancistrobenomine b and related 5,1'-coupled naphthylisoquinoline alkaloids from the chinese liana ancistrocladus tectorius. | a striking feature of the metabolite pattern of the southeast asian liana ancistrocladus tectorius (ancistrocladaceae) is the predominance of 5,1'-coupled naphthylisoquinoline alkaloids. about 20 alkaloids of this coupling type have so far been discovered in this plant species. here, we report on the isolation of four new 5,1'-linked naphthylisoquinolines from the twigs and stems of a. tectorius. two of them, the ancistrobenomines b (5) and c (6), belong to the very rare group of alkaloids with ... | 2017 | 28688886 |
| bistacrines as potential antitrypanosomal agents. | human african trypanosomiasis (hat) is caused by two subspecies of the genus trypanosoma, namely trypanosoma brucei rhodesiense and trypanosoma brucei gambiense. the disease is fatal if left untreated and therapy is limited due to only five non-adequate drugs currently available. in preliminary studies, dimeric tacrine derivatives were found to inhibit parasite growth with ic50-values in the nanomolar concentration range. this prompted the synthesis of a small, but smart library of monomeric and ... | 2017 | 28698054 |
| steroid alkaloids from holarrhena africana with strong activity against trypanosoma brucei rhodesiense. | in our continued search for natural compounds with activity against trypanosoma brucei, causative agent of human african trypanosomiasis (hat, "sleeping sickness"), we have investigated extracts from the leaves and bark of the west african holarrhenaafricana (syn. holarrhena floribunda; apocynaceae). the extracts and their alkaloid-enriched fractions displayed promising in vitro activity against bloodstream forms of t. brucei rhodesiense (tbr; east african hat). bioactivity-guided chromatographi ... | 2017 | 28684718 |
| host-seeking efficiency can explain population dynamics of the tsetse fly glossina morsitans morsitans in response to host density decline. | females of all blood-feeding arthropod vectors must find and feed on a host in order to produce offspring. for tsetse-vectors of the trypanosomes that cause human and animal african trypanosomiasis-the problem is more extreme, since both sexes feed solely on blood. host location is thus essential both for survival and reproduction. host population density should therefore be an important driver of population dynamics for haematophagous insects, and particularly for tsetse, but the role of host d ... | 2017 | 28672001 |
| the double-edged sword of evolution. | two gene variants provide different levels of protection against sleeping sickness, but this comes with an increased risk of developing chronic kidney disease. | 2017 | 28671870 |
| polymerase chain reaction identification of trypanosoma brucei rhodesiense in wild tsetse flies from nkhotakota wildlife reserve, malawi. | trypanosoma brucei rhodesiense is the causative agent of acute human african trypanosomiasis. identification of t. b. rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessng human disease risk, and monitoring spatiotemporal trends and impact of control interventions. accurate detection and characterisation of trypanosomes in vectors relies on molecular techniques. for the first time in malawi, a molecular technique has been used to detect trypanosomes in ... | 2017 | 28567189 |
| apol1 renal risk variants have contrasting resistance and susceptibility associations with african trypanosomiasis. | reduced susceptibility to infectious disease can increase the frequency of otherwise deleterious alleles. in populations of african ancestry, two apolipoprotein-l1 (apol1) variants with a recessive kidney disease risk, named g1 and g2, occur at high frequency. apol1 is a trypanolytic protein that confers innate resistance to most african trypanosomes, but not trypanosoma brucei rhodesiense or t.b. gambiense, which cause human african trypanosomiasis. in this case-control study, we test the preva ... | 2017 | 28537557 |
| the structure of serum resistance-associated protein and its implications for human african trypanosomiasis. | only two trypanosome subspecies are able to cause human african trypanosomiasis. to establish an infection in human blood, they must overcome the innate immune system by resisting the toxic effects of trypanolytic factor 1 and trypanolytic factor 2 (refs. 1,2). these lipoprotein complexes contain an active, pore-forming component, apolipoprotein l1 (apol1), that causes trypanosome cell death 3 . one of the two human-infective subspecies, trypanosoma brucei rhodesiense, differs from non-infective ... | 2018 | 29358741 |
| antiprotozoal sesquiterpene lactones and other constituents from tarchonanthus camphoratus and schkuhria pinnata. | in continuation of a search for new antiprotozoal agents from plants of the family asteraceae, tarchonanthus camphoratus and schkuhria pinnata have been investigated. by following the promising in vitro activity of the dichloromethane extracts from their aerial parts, bioassay-guided chromatographic isolation yielded two known sesquiterpene lactones (1 and 2) from t. camphoratus and 20 known compounds of this type from s. pinnata. from the latter, a new eudesmanolide, (1r*,5s*,6r*,7r*,8r*,10r*)- ... | 2017 | 29244495 |
| inhibitory effects of (+)-spectaline and iso-6-spectaline from senna spectabilis on the growth and ultrastructure of human-infective species trypanosoma brucei rhodesiense bloodstream form. | in our ongoing work searching for new trypanocidal lead compounds from malaysian plants, two known piperidine alkaloids (+)-spectaline (1) and iso-6-spectaline (2) were isolated from the leaves of senna spectabilis (sin. cassia spectabilis). analysis of the 1h and 13c nmr spectra showed that 1 and 2 presented analytical and spectroscopic data in full agreement with those published in the literature. all compounds were screened in vitro against trypanosoma brucei rhodesiense in comparison to the ... | 2017 | 29175017 |
| indole and benzimidazole bichalcophenes: synthesis, dna binding and antiparasitic activity. | a novel series of indole and benzimidazole bichalcophene diamidine derivatives were prepared to study their antimicrobial activity against the tropical parasites causing african sleeping sickness and malaria. the dicyanoindoles needed to synthesize the target diamidines were obtained through stille coupling reactions while the bis-cyanobenzimidazoles intermediates were made via condensation/cyclization reactions of different aldehydes with 4-cyano-1,2-diaminobenzene. different amidine synthesis ... | 2018 | 29126729 |
| relationship between trypanosoma brucei rhodesiense genetic diversity and clinical spectrum among sleeping sickness patients in uganda. | human african trypanosomiasis (hat) due to trypanosoma brucei rhodesiense in east and southern africa is reported to be clinically diverse. we tested the hypothesis that this clinical diversity is associated with a variation in trypanosome genotypes. | 2017 | 29078807 |
| estimating the economic and social consequences for patients diagnosed with human african trypanosomiasis in muchinga, lusaka and eastern provinces of zambia (2004-2014). | acute human african trypanosomiasis (rhat) caused by trypanosoma brucei rhodesiense is associated with high mortality and is fatal if left untreated. only a few studies have examined the psychological, social and economic impacts of rhat. in this study, mixed qualitative and quantitative research methods were used to evaluate the socio-economic impacts of rhat in mambwe, rufunsa, mpika and chama districts of zambia. | 2017 | 29017597 |
| the genomic landscape of african populations in health and disease. | a deeper appreciation of the complex architecture of african genomes is critical to the global effort to understand human history, biology and differential distribution of disease by geography and ancestry. here, we report on how the growing engagement of african populations in genome science is providing new insights into the forces that shaped human genomes before and after the out-of-africa migrations. as a result of this human evolutionary history, african ancestry populations have the great ... | 2017 | 28977439 |
| beyond immune escape: a variant surface glycoprotein causes suramin resistance in trypanosoma brucei. | suramin is one of the first drugs developed in a medicinal chemistry program (bayer, 1916), and it is still the treatment of choice for the hemolymphatic stage of african sleeping sickness caused by trypanosoma brucei rhodesiense. cellular uptake of suramin occurs by endocytosis, and reverse genetic studies with t. b. brucei have linked downregulation of the endocytic pathway to suramin resistance. here we show that forward selection for suramin resistance in t. brucei spp. cultures is fast, hig ... | 2018 | 28963732 |
| metabolic profiling of central nervous system disease in trypanosoma brucei rhodesiense infection. | the progression of human african trypanosomiasis from the early hemolymphatic stage to the late meningoencephalitic stage is of critical diagnostic importance as it determines the choice of potentially toxic drug regimens. current diagnostic criteria involving analysis of cerebrospinal fluid (csf) for parasites and/or pleocytosis are sensitive, but recent evidence suggests that specificity may be poor. | 2017 | 28927234 |
| hsp70/j-protein machinery from glossina morsitans morsitans, vector of african trypanosomiasis. | tsetse flies (glossina spp.) are the sole vectors of the protozoan parasites of the genus trypanosoma, the causative agents of african trypanosomiasis. species of glossina differ in vector competence and glossina morsitans morsitans is associated with transmission of trypanosoma brucei rhodesiense, which causes an acute and often fatal form of african trypanosomiasis. heat shock proteins are evolutionarily conserved proteins that play critical roles in proteostasis. the activity of heat shock pr ... | 2017 | 28902917 |