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stage-specific gene expression in lymphatic filarial nematodes.lymphatic filarial nematodes remain a significant cause of morbidity throughout much of the tropics. one approach to the development of rational control methods is an improved understanding of the basic biology of these organisms in relation to the mechanisms used to complete their life cycles. in this article, eileen devaney, sam martin and fiona thompson review new approaches to defining stage-specific molecules in filarial nematodes, and discuss their recent work on the isolation and characte ...199615275274
[ultrastructural basis of interactions between prokaryotes and eukaryotes in different symbiotic models].this paper reviews the author's contribution to the knowledge of the ultrastructural basis of the prokaryote-eukaryote interactions in different models assessed by an ultrastructural approach. in agreement with the hypothesis of the origin of eukaryotic cells, which are chimeras of several prokaryotes with different morpho-functional specializations, symbiosis had major consequence for evolution of life. in arthropods, one of the most successful lifestyles, the presence of endosymbiotic prokaryo ...200415305681
a model for the dynamics of human lymphatic filariasis.in this paper, bryan gren fell, edwin michael and david denham review the appropriateness of feline filariasis as a model of the population dynamics of human lymphatic filarial infection and disease. because of the longevity of infection and our inability to measure the adult parasite population in humans, research in filariasis is particularly dependent on the use of laboratory animal models. we demonstrate that brugia pahangi infection patterns in the cat closely parallel those of brugia and w ...199115463403
a gene family of cathepsin l-like proteases of filarial nematodes are associated with larval molting and cuticle and eggshell remodeling.cysteine proteinases are involved in a variety of important biological processes and have been implicated in molting and tissue remodeling in free living and parasitic nematodes. we show that in the lymphatic filarial nematode brugia pahangi molting of third-stage larvae (l3) to fourth-stage larvae is dependent on the activity of a cathepsin l-like cysteine protease (cpl), which can be detected in the excretory/secretory (es) products of molting l3. directed cloning of a cysteine protease gene i ...200415478801
delayed macrofilaricidal activity of diethylcarbamazine against brugia pahangi in mongolian jirds.the macrofilaricidal activity of diethylcarbamazine (dec) was confirmed in jirds infected with brugia pahangi. seventy jirds were inoculated subcutaneously with 100 infective larvae. at 20 weeks post-infection, the microfilaraemic jirds were divided into two groups, untreated and treated. for the treated group, 200 mg kg(-1) of dec was injected intraperitoneally for 5 consecutive days. one, 4, 8, 12, 16 and 27 weeks after the final treatment, 4-7 jirds in each group were sacrificed to measure ad ...200415575984
mosquito transmission modulates the immune response in mice infected with the l3 of brugia pahangi.mice infected by syringe inoculation with the l3 of the filarial nematode brugia pahangi generate a strong th2 response. in this study we compared immune responses in mice infected via syringe with those infected by mosquito transmission of l3. levels of antigen-specific il-4, il-5 and il-10 were significantly reduced in mice infected via mosquito. a possible explanation of these results was that mice infected via mosquito received fewer l3 than those infected via syringe. to investigate this po ...200415679633
b cells play a regulatory role in mice infected with the l3 of brugia pahangi.mice infected with the l3 of the filarial nematode brugia pahangi make a strong t(h)2 response characterized by elevated levels of antigen-specific il-4, il-5 and il-10. here we show that b cells from these animals are the major proliferating population in vitro with depletion of b cells or infection of mumt mice, resulting in reduced levels of antigen-specific proliferation. b cells also act as antigen-presenting cells (apc) to cd4(+) cells as demonstrated by the switch in cytokine profiles upo ...200515724063
filarial susceptibility and effects of wolbachia in aedes pseudoscutellaris mosquitoes.the mosquito aedes pseudoscutellaris (theobald), a member of the aedes (stegomyia) scutellaris complex (diptera: culicidae), is an important vector of subperiodic wuchereria bancrofti (cobbold) (spirurida: onchocercidae), causing human lymphatic filariasis, on south pacific islands. maternal inheritance of filarial susceptibility in the complex has previously been asserted, and larval tetracycline treatment reduced susceptibility; the maternally inherited wolbachia in these mosquitoes were sugge ...200515752178
macrofilaricidal and microfilaricidal effects of neurolaena lobata, a guatemalan medicinal plant, on brugia pahangi.twelve extracts of 11 guatemalan medicinal plants were initially screened in vitro for potential macrofilaricidal activity against brugia pahangi, a lymphatic dwelling filarial worm, using concentrations from 125 to 1000 microg ml(-1) of each extract that could be dissolved in the culture medium. of 12 extracts used, the ethanol extract of leaves of neurolaena lobata showed the strongest activity against the motility of adult worms. subsequently, the extract of n. lobata was extensively examined ...200515831109
hsp90 is essential in the filarial nematode brugia pahangi.the development of a compound with activity against filarial nematodes (a 'macrofilaricide') has been a long-standing goal of the world health organization. however, adult filariae have proved remarkably difficult to kill. to some extent this reflects a lack of understanding of key pathways and processes in filarial nematodes that may be suitable targets for chemotherapy. in this paper we show that geldanamycin (ga), a specific inhibitor of the activity of the heat shock protein 90 (hsp90) famil ...200515862576
regulatory t cells modulate th2 responses induced by brugia pahangi third-stage larvae.infection of balb/c mice with brugia pahangi third-stage larvae (l3) results in the production of interleukin-4 (il-4), il-5, and il-10 with a resultant down-regulation in th1 responses. previously, this was thought to reflect a skewing of immune responses towards a th2 phenotype by the infective stage of the parasite. in this study, we show that exposure to the l3 of brugia also induces the expansion of a population of cd4 cells that express cd25 and cytotoxic-t-lymphocyte-associated antigen 4 ...200515972491
kinetics of t cell cytokine gene expression in gerbils after a primary subcutaneous brugia pahangi infection.the majority of patients infected with lymphatic filariae are microfilaremic but tend to manifest little obvious pathology because of the infections. data collected from the mongolian gerbil-brugia spp. model for human lymphatic filariasis suggest this experimental animal model system most closely represents this patient group and will be useful in studying immunological parameters associated with chronic infections. this article reports the quantitation of interleukin (il)-4, il-5, il-10, il-13 ...200515986598
critical role for igm in host protection in experimental filarial infection.we have previously shown that b cells (in particular b1 cells) are important in host protection against brugian infections in a murine i.p. model. in this study, we show that mice deficient in circulating igm (secigm-/-), but otherwise normal in their humoral responses, manifest a significant impairment in worm elimination, suggesting that one critical b cell function is the production of ag-specific igm. efficient elimination of larvae is igm dependent for both primary and challenge infections. ...200516034125
differential effects of diethylcarbamazine, tetracycline and the combination on brugia pahangi adult females in vitro.anti-filarial effects of diethylcarbamazine (dec), tetracycline (tc) and the combination on brugia pahangi adult females were studied in 7-day cell-free culture, in terms of microfilaria release, parasite motility, mtt assay for parasite viability and embryogram. tc 50 microg/ml (tc50) effectively reduced microfilaria release from day 1 of culture. combined with dec 100 microg/ml (dec100) or dec 500 microg/ml (dec500), microfilaria release reduced further and synergistically. tc50 also reduced m ...200516103005
[diagnostic tests: filaria]. 200516111250
detection and differentiation of filarial parasites by universal primers and polymerase chain reaction-restriction fragment length polymorphism analysis.filarial nematode parasites are a serious cause of morbidity in humans and animals. identification of filarial infection using traditional morphologic criteria can be difficult and lead to misdiagnosis. we report on a polymerase chain reaction-restriction fragment length polymorphism (pcr-rflp)-based method to detect and differentiate a broad range of filarial species in a single pcr. the first internal transcribed spacer 1 (its1) along with the flanking 18s and 5.8s ribosomal dna (rdna) were is ...200516282300
eosinophils, but not eosinophil peroxidase or major basic protein, are important for host protection in experimental brugia pahangi infection.the attenuation of eosinophilia by the administration of monoclonal antibodies to ccr3 consistently correlates with impairment in worm elimination following primary intraperitoneal brugia pahangi infections in mice. host protection was unimpaired in mice deficient in eosinophil peroxidase (epo) or major basic protein 1 (mbp-1), suggesting that eosinophils are essential in host protection but that neither epo nor mbp-1 alone is.200516299347
cloning and characterization of the cu/zn superoxide dismutase of trichinella pseudospiralis.copper/zinc (cu/zn) superoxide dismutase (sod) activity was identified for the first time in both crude somatic extracts (ce) and excretory/secretory (e/s) products of trichinella pseudospiralis. it was the dominant sod in infective-stage larvae. native polyacrylamide gel electrophoresis of ce and e/s products yielded a prominent band, which was cyanide-sensitive and was partly inhibited by hydrogen peroxide in sod assay. cytosolic cu/zn sod was cloned. the 471-bp full-length cdna sequence conta ...200616341881
the ultrastructure of the gravid uterus of brugia pahangi, another rich source of antigen of the filarial parasite.the gravid uterus with zygotes and microfilariae in utero of brugia pahangi, a rich source of antigen as revealed by a recent immunofluorescent technique, were studied ultrastructurally. the epithelial cells of uterus show ultrastructural features of synthetically active cells. their secretions may provide nutrients for the egg in utero. on the basal side, the uterine epithelial cells may also secrete substances to form the basal lamina of the uterus which is rather thick and irregularly fused w ...200516438131
cytokine profiles of filarial granulomas in jirds infected with brugia pahangi.a granulomatous inflammatory response develops in jirds infected subcutaneously or intraperitoneally with filarial nematodes namely brugia pahangi and b. malayi. previous studies by light and electron microscopy have shown cellular inflammatory responses in and around these granulomas. furthermore, the cellular inflammatory responses of granulomas found in the lymphatics and peritoneal cavity appear to be similar. the purpose of this study was to determine the cytokine profiles of granulomas in ...200616542426
inflammatory responses to migrating brugia pahangi third-stage larvae.despite being central to parasite establishment and subsequent host pathological and immunologic responses, host-parasite interactions during early third-stage filarial larva (l3) migration are poorly understood. these studies aimed to define early tissue migration of brugia pahangi l3 in the gerbil (meriones unguiculatus) and measure host cellular responses during this period. gerbils were intradermally inoculated in the hind limb with 100 b. pahangi l3, and necropsies were performed at various ...200616552066
differential display of genes expressed in the filarial nematode litomosoides sigmodontis reveals a putative phosphate permease up-regulated after depletion of wolbachia endobacteria.mutualist symbiotic wolbachia endobacteria are found in most filarial nematodes. wolbachia are essential for embryogenesis and for larval development into adults, and thus represent a new target for anti-filarial drug development. tetracycline antibiotics deplete wolbachia in animal model filaria litomosoides sigmodontis and brugia pahangi, as well as in the human parasites brugia malayi, onchocerca volvulus and wuchereria bancrofti. very little is known about the molecular details of the symbio ...200616616613
tissue migration capability of larval and adult brugia pahangi.infection with mosquito-born filarial nematodes occurs when hosts are bitten by a vector carrying the infective third stage larvae (l3) of the parasites. these larvae, deposited on the skin by the feeding mosquito, are presumed to enter the skin via the vector-induced puncture wound. larvae of brugia spp. must then migrate from the entry site, penetrate various skin layers, and locate a lymphatic vessel that leads to their lymphatic predilection site. we have recently established an intradermal ...200616629314
profiling the cellular immune response to multiple brugia pahangi infections in a susceptible host.human lymphatic filariasis is caused primarily by brugia malayi and wuchereria bancroffi. unraveling this disease is complex, as people living in endemic areas exhibit a vast array of clinical states and immune responses. the mongolian gerbil (meriones unguiculatus)-b. pahangi model of human lymphatic filariasis has provided much information on immune parameters associated with filarial infection. prior investigations in our laboratory have shown that gerbils closely mimic a subset of patients c ...200517089749
penetration of the mosquito midgut is not required for brugia pahangi microfilariae to avoid the melanotic encapsulation response of armigeres subalbatus.insect vectors of disease have the capacity to respond to, and prevent further development of, parasites and pathogens using a response known as melanotic encapsulation. the naturally-occurring armigeres subalbatus-brugia spp. system provides an excellent way to investigate melanotic encapsulation and immune recognition in a mosquito host, because brugia malayi microfilariae (mf) acquired via a blood meal are rapidly melanized in the body cavity of ar. subalbatus, but brugia pahangi mf evade or ...200717116367
temporary shift of microfilariae of brugia pahangi from the lungs to muscles in mongolian jirds, meriones unguiculatus, after a single injection of diethylcarbamazine.a single-dose treatment with diethylcarbamazine (dec) reduced microfilaria (mf) counts of brugia pahangi by >90% at 30 min post-treatment in mongolian jirds (meriones unguiculatus). the reduction was followed by a rapid increase in microfilaremia, with the count reaching pretreatment level in 3 hr. the mechanisms behind this temporary reduction of mf were investigated. without treatment, mf accumulated in the lungs. at 30 min post-treatment, they had moved from the lungs and accumulated in the m ...200617152953
response of armigeres subalbatus (diptera: culicidae) to intraperitoneally isolated brugia spp. microfilariae.the relationship between mosquito and parasite involves a delicate balance that is influenced not only by the mosquito but also by parasite determinants. using the biologically and morphologically similar parasites brugia malayi and brugia pahangi and the mosquito armigeres subalbatus (coquillett) (diptera: culicidae), it should be possible to dissect out the key elements involved in initiating or avoiding an immune response, known as melanotic encapsulation, because in this mosquito b. malayi m ...200717427699
the observation of microfilarial rate and density in cats inoculated with increasing numbers of brugia pahangi infective larvae.having close kinship to brugia malayi, b. pahangi is a member of the family filariidae, which causes lymphatic filariasis in dogs and cats. although this nematode is unlikely to cause a zoonotic disease in humans, study of the b. pahangi life cycle may help control human filariasis. the objective of this study was to examine microfilarial rates and densities of b. pahangi in experimentally induced infections in cats as a relative measurement. cats were infected with 3 different amounts of 3rd-st ...200617547050
acute but not chronic macrophage recruitment in filarial infections in mice is dependent on c-c chemokine ligand 2.macrophages play an important role in the formation of granulomas and the clearance of brugia pahangi infections in mice. however, the factors responsible for the recruitment of these cells to the site of infection are not known. in this study we examined the role of the c-c chemokine ligand 2 (ccl2; also known as macrophage chemotactic factor - mcp1) in macrophage recruitment in intraperitoneal infections with b. pahangi. we observed that ccl2 was expressed by peritoneal exudate cells and was p ...200717650181
confirmation of elimination of lymphatic filariasis by an igg4 enzyme-linked immunosorbent assay with urine samples in yongjia, zhejiang province and gaoan, jiangxi province, people's republic of china.a sensitive and specific igg4 enzyme-linked immunosorbent assay (elisa) with urine samples has been reported. to confirm elimination of bancroftian filariasis, the elisa was used in a study conducted in yongjia county and gaoan city, people's republic of china, where filariasis elimination was declared, with 10,409 students 5-16 years of age. the antibody positive rates were 0.08% in yongjia and 0.34% in gaoan. all positive samples were re-examined and found to be negative. our results show that ...200717690407
brugia pahangi: in vivo tissue migration of early l3 alters gene expression.events occurring during early filarial nematode migrations are central to parasite establishment but rarely studied. brugia pahangi larvae injected intradermal (id) into the hind limb of the gerbil (meriones unguiculatus) can be recovered from the popliteal lymph node (pop) at 3 days post-infection (dpi). they have been designated migrating larvae (idl3). alternatively, l3 recovered at 3dpi from the peritoneal cavity (ipl3) do not migrate. subtracted cdna libraries using idl3 and ipl3 revealed d ...200817706647
comparison of the pharmacokinetics of moxidectin and ivermectin after oral administration to beagle dogs.this study compares plasma disposition kinetics of ivermectin and moxidectin after oral administration to beagle dogs experimentally infected with the filarial parasite, brugia pahangi. sixteen dogs were selected and randomly allocated into two groups of eight dogs each. animals in each group received either ivermectin or moxidectin by oral route at a dose of 250 microg/kg. blood samples were collected from 0.5 h up to 56 days post-treatment and the plasma was analysed by high performance liquid ...200717847063
determinants of memory in experimental filarial infections in mice.in this communication, we examine the determinants and duration of memory responses against filarial parasites using an intraperitoneal mouse model of brugia pahangi infection. we assessed the role of t cells in the memory response against b. pahangi larvae by transferring splenic t cells from wild-type mice primed with l3 into t-cell-deficient mice. we found that mice reconstituted with primed t cells cleared intraperitoneal infections with infective larvae in an accelerated manner. to determin ...200717944746
mosquito transcriptome changes and filarial worm resistance in armigeres subalbatus.armigeres subalbatus is a natural vector of the filarial worm brugia pahangi, but it rapidly and proficiently kills brugia malayi microfilariae by melanotic encapsulation. because b. malayi and b. pahangi are morphologically and biologically similar, the armigeres-brugia system serves as a valuable model for studying the resistance mechanisms in mosquito vectors. we have initiated transcriptome profiling studies in ar. subalbatus to identify molecular components involved in b. malayi refractorin ...200718088420
in vitro chemotaxis of brugia pahangi infective larvae to the sera and hemolymph of mammals and lower animals.the jird (mongolian gerbil) is a highly susceptible experimental host for the lymphatic filarial nematode, brugia pahangi. the chemotactic activity of serum from this host for b. pahangi infective larvae was compared in vitro to that of sera or hemolymph of a wide variety of other organisms including mammals, reptiles, fishes and invertebrates. the range of the chemotactic index (ci) was from 96.0 for the jird to 56.2 for a snail. an average of ci of saline control was 4.5. significant chemotact ...200818243775
a novel gene from brugia sp. that encodes a cytotoxic fatty acid binding protein allergen recognized by canine monoclonal ige and serum ige from infected dogs.brugia pahangi infection of dogs is a well characterized model of human lymphatic filariasis in which sera consistently show igg or ige reactivity to a 35-kda antigen. using dog lymph node b cells, we previously established a heterohybridoma cell line producing canine monoclonal ige (cmab 2.39) that activates and degranulates canine mast cells, and specifically recognizes a 35-kda b. pahangi antigen. by affinity purification and sequencing of the native protein from b. pahangi adults, a 19-amino ...200718314684
presence and gradual disappearance of filaria-specific urinary igg4 in babies born to antibody-positive mothers: a 2-year follow-up study.a total of 14 sri lankan pregnant women, who were anti-brugia pahangi urinary igg4 positive, and their 14 newborn babies were followed up for the urinary antibody for 2 years by enzyme-linked immunosorbent assay. eight babies showed positive igg4 reaction, at least once within 4 months after birth. urinary antibody titers of mothers and their babies measured around the perinatal period showed a significant positive correlation, suggesting that baby's igg4 was transferred from the mother through ...200818502681
inferring the phylogenetic position of brugia pahangi using 18s ribosomal rna (18s rrna) gene sequence.this paper presents the first reported use of 18s rrna gene sequence to determine the phylogeny of brugia pahangi. the 18s rrna nucleotide sequence of a malaysian b. pahangi isolate was obtained by pcr cloning and sequencing. the sequence was compared with 18s rrna sequences of other nematodes, including those of some filarial nematodes. multiple alignment and homology analysis suggest that b. pahangi is closely related to b. malayi and wuchereria bancrofti. phylogenetic trees constructed using ...200818600209
evaluation of the function of a type i peritrophic matrix as a physical barrier for midgut epithelium invasion by mosquito-borne pathogens in aedes aegypti.in addition to modulating blood meal digestion and protecting the midgut epithelial cells from mechanical and chemical damage, a biological function attributed to the mosquito type i peritrophic matrix (pm) is preventing or reducing pathogen invasion, especially from plasmodium spp. previously, we demonstrated that chitin is an essential component of the pm and is synthesized de novo in response to blood feeding in aedes aegypti. therefore, knocking down chitin synthase expression by rna interfe ...200818627241
intraspecies variation of brugia spp. in cat reservoirs using complete its sequences.the internal transcribed spacer (its) region was used to study the intraspecies variation of brugia spp. in cat reservoirs. blood specimens from seven naturally infected cats were collected from two different geographical brugian-endemic areas in thailand. the dnapar tree of these brugia spp. was constructed using a maximum likelihood approach based on its nucleotide sequences and was compared to those of brugia malayi, brugia pahangi, and dirofilaria immitis that were previously reported in gen ...200919205740
differentiation of brugia malayi and brugia pahangi by pcr-rflp of its1 and its2.lymphatic filariasis has been targeted by the world health organization for elimination by the year 2020. malayan filariasis, caused by brugia malayi, is endemic in southern thailand where domestic cats serve as a major reservoir host. however, in nature, domestic cats also carry b. pahangi infection. in addition to chemotherapy and vector control, control in reservoir hosts is necessary to achieve the elimination of the disease. therefore, differentiation between b. malayi and b. pahangi in the ...200319230574
molecular characterization and phylogenetic evaluation of the hsp90 gene from selected nematodes.while multiple genes are optimal for corroborating nematode phylogenies, only a few are commonly used. here we examine the phylogenetic potential of the nuclear hsp90 chaperone gene. we used degenerate primers to obtain partial hsp90 sequences from several plant-parasitic and free-living nematodes. hsp90 was single-copy in heterodera glycines and meloidogyne javanica, similar to the situation for caenorhabditis elegans. the full-length h. glycines hsp90 protein sequence showed homology to sequen ...200419262827
molecular genetics analysis for co-infection of brugia malayi and brugia pahangi in cat reservoirs based on internal transcribed spacer region 1.this study described the diagnosis of a mixed infection of brugia malayi and brugia pahangi in a single domestic cat using the internal transcribed spacer 1 (its1) region. following polymerase chain reaction amplification of the its1 region, the 580 bp amplicon was cloned, and 29 white colonies were randomly selected for dna sequencing and phylogenetic tree construction. a dna parsimony tree generated two groups of brugia spp with one group containing 6 clones corresponding to b. pahangi and the ...200919323030
functional genomics of hsp-90 in parasitic and free-living nematodes.heat shock protein 90 (hsp-90) is a highly conserved essential protein in eukaryotes. here we describe the molecular characterisation of hsp-90 from three nematodes, the free-living caenorhabditis elegans (ce) and the parasitic worms brugia pahangi (bp) and haemonchus contortus (hc). these molecules were functionally characterised by rescue of a ce-daf-21 (hsp-90) null mutant. our results show a gradient of rescue: the c. elegans endogenous gene provided full rescue of the daf-21 mutant, while h ...200919401205
identification of antigenic brugia adult worm proteins by peptide mass fingerprinting.with the recent completion of the brugia malayi genome, proteomics offers a new resource for a deeper understanding of the biology of filarial parasites. we employed 2-dimensional (2d) gel electrophoresis followed by peptide mass fingerprinting on a matrix-assisted laser desorption/ionization time-of-flight (maldi-tof) mass spectrometer to identify brugia adult worm proteins and then determined which proteins were recognized by the host humoral immune response. we identified 18 unique proteins, ...200919537848
high resolution melting real-time pcr for rapid discrimination between brugia malayi and brugia pahangi.to identify two closely related brugia malayi and b. pahangi in cat reservoirs by using high resolution melting real-time pcr (hrm real-time pcr).200919705544
immune activation by life-shortening wolbachia and reduced filarial competence in mosquitoes.wolbachia strain wmelpop reduces the longevity of its drosophila melanogaster host and, when introduced into the mosquito aedes aegypti, halves its life span. we show that wmelpop induces up-regulation of the mosquito's innate immune system and that its presence inhibits the development of filarial nematodes in the mosquito. these data suggest that wmelpop could be used in the global effort to eliminate lymphatic filariasis and possibly for the control of other mosquito-borne parasites where imm ...200919797660
use of microarray hybridization to identify brugia genes involved in mosquito infectivity.brugia malayi and brugia pahangi microfilariae (mf) require a maturation period of at least 5 days in the mammalian host to successfully infect laboratory mosquitoes. this maturation process coincides with changes in the surface composition of mf that likely are associated with changes in gene expression. to test this hypothesis, we verified the differential infectivity of immature (< or =3 day) and mature (>30 day) brugia mf for black-eyed liverpool strain of aedes aegypti and then assessed tra ...200919894065
differential detection of brugia malayi and brugia pahangi by real-time fluorescence resonance energy transfer pcr and its evaluation for diagnosis of b. pahangi-infected dogs.a real-time fluorescence resonance energy transfer pcr combined with melting curve analysis was developed for differentiating brugia malayi and brugia pahangi dna in host blood using one set of primers and fluorophore-labeled hybridization probes specific for hhai repetitive dna. the differentiation of both species was based on their melting temperatures (tm). the mean tm +/- sd of b. malayi and b. pahangi were 56.18+/-0.21 and 52.49+/-0.07, respectively. the method was used for the molecular de ...201020066436
estimation of parameters for macroparasite population evolution using approximate bayesian computation.we estimate the parameters of a stochastic process model for a macroparasite population within a host using approximate bayesian computation (abc). the immunity of the host is an unobserved model variable and only mature macroparasites at sacrifice of the host are counted. with very limited data, process rates are inferred reasonably precisely. modeling involves a three variable markov process for which the observed data likelihood is computationally intractable. abc methods are particularly use ...201120345496
differential transcript expression between the microfilariae of the filarial nematodes, brugia malayi and b. pahangi.brugia malayi and b. pahangi are two closely related nematodes that cause filariasis in humans and animals. however, b. pahangi microfilariae are able to develop in and be transmitted by the mosquito, armigeres subalbatus, whereas most b. malayi are rapidly melanized and destroyed within the mosquito hemocoel. a cross-species microarray analysis employing the b. malayi v2 array was carried out to determine the transcriptional differences between b. malayi and b. pahangi microfilariae with simila ...201020370932
mosquito transcriptome profiles and filarial worm susceptibility in armigeres subalbatus.armigeres subalbatus is a natural vector of the filarial worm brugia pahangi, but it kills brugia malayi microfilariae by melanotic encapsulation. because b. malayi and b. pahangi are morphologically and biologically similar, comparing ar. subalbatus-b. pahangi susceptibility and ar. subalbatus-b. malayi refractoriness could provide significant insight into recognition mechanisms required to mount an effective anti-filarial worm immune response in the mosquito, as well as provide considerable de ...201020421927
assay strategies for the discovery and validation of therapeutics targeting brugia pahangi hsp90.the chemotherapy of lymphatic filariasis relies upon drugs such as diethylcarbamazine and ivermectin that largely target the microfilarial stages of the parasite, necessitating continued treatment over the long reproductive life span of the adult worm. the identification of compounds that target adult worms has been a long-term goal of who. here we describe a fluorescence polarization assay for the identification of compounds that target hsp90 in adult filarial worms. the assay was originally de ...201020559560
brugia filariasis differentially modulates persistent helicobacter pylori gastritis in the gerbil model.in select helicobacter pylori-infected populations with low gastric cancer, nematode coinfections are common and both helicobacter gastritis and filariasis are modeled in gerbils. we evaluated gastritis, worm counts, tissue cytokine gene expression levels and th1/th2-associated antibody responses in h. pylori and brugia pahangi mono- and coinfected gerbils. h. pylori-associated gastritis indices were significantly lower 21 weeks post-infection in coinfected gerbils (p < or = 0.05) and were inver ...201020685294
zoonotic brugia pahangi filariasis in a suburbia of kuala lumpur city, malaysia.five local malaysian patients with clinical manifestations consistent with lymphatic filariasis were referred to our medical centre between 2003 and 2006. although no microfilariae (mf) were detected in their nocturnal blood samples, all were diagnosed to have lymphatic filariasis on the basis of clinical findings and positive serology results. pcr on their blood samples revealed that two of the patients were infected with brugia pahangi, an animal filarial worm hitherto not known to cause human ...201020951228
granuloma formation around filarial larvae triggered by host responses to an excretory/secretory antigen.in previous studies using a murine model of filarial infection, granuloma formation was found to be a most important host-protective mechanism. we have also shown that in vitro cytoadherence is a surrogate for the formation of antifilarial granulomas in vivo and that it requires "alternatively activated" host cells and a source of antifilarial antibody. we show here that antibodies against l3 excretory/secretory (e/s) products can facilitate in vitro cytoadherence. we generated a set of hybridom ...201021078849
effects of doxycycline on early infections of dirofilaria immitis in dogs.the antifilarial effects of tetracycline drugs were first demonstrated when they were found to be highly effective against l(3) and l(4) of brugia pahangi and litomosoides sigmodontis in rodent models. tetracyclines are also now known to have activity against microfilariae and adult dirofilaria immitis, but assessment of their activity against larval and juvenile heartworms has not been reported previously. this study assessed the effects of doxycycline administered orally at 10mg/kg twice daily ...201121345592
filarial worms reduce plasmodium infectivity in mosquitoes.co-occurrence of malaria and filarial worm parasites has been reported, but little is known about the interaction between filarial worm and malaria parasites with the same anopheles vector. herein, we present data evaluating the interaction between wuchereria bancrofti and anopheles punctulatus in papua new guinea (png). our field studies in png demonstrated that an. punctulatus utilizes the melanization immune response as a natural mechanism of filarial worm resistance against invading w. bancr ...201121347449
expression and characterization of cu/zn superoxide dismutase from wuchereria bancrofti.the cu/zn superoxide dismutase gene from wuchereria bancrofti (cu/zn wbsod) was isolated by pcr using degeneracy primers. the complete cu/zn wbsod consisted of 1,032 nucleotides containing 4 exons (477 nucleotides) and 3 introns. the molecular phylogenetic analysis of the cu/zn wbsod gene in comparison with those from other organisms revealed that the gene was classified in the same clade to those of filarial brugia malayi and brugia pahangi (bootstrap value at 90). the nucleotide and deduced am ...201121796387
A 22 year follow-up study on lymphatic filariasis in Tanzania: analysis of immunological responsiveness in relation to long-term infection pattern.Seventy-one individuals who had been examined for Wuchereria bancrofti microfilaraemia in 1975, some of whom had been offered mass treatment with diethylcarbamazine (DEC) in subsequent years, were re-identified in 1996 and examined for microfilaraemia, circulating filarial antigenemia and cellular and humoral immunoresponsiveness to crude antigen homogenates prepared from Brugia pahangi parasite material. 85.9% of the study individuals had the same infection status in 1975 and 1996, suggesting s ...201121964049
In vitro chemotactic responses of Brugia pahangi infective larvae to sodium ions.In vitro chemotactic responses of infective third-stage larvae (L3) of Brugia pahangi to NaCl, Na2HPO4, KCl, K2HPO4, MgCl2 and CaCl2 were assessed. Compared to deionized water as a control, 200 mm NaCl and 100 mm Na2HPO4 significantly attracted L3 (P < 0.01 and P < 0.01), whereas L3 were likely to avoid 200 mm KCl and 100 mm K2HPO4 (P < 0.05 and P < 0.05). L3 showed no significant tendency to avoid or to be attracted to 200 mm CaCl2 and 200 mm MgCl2. Furthermore, NaCl exhibited a significant che ...201122030560
diversity in parasitic nematode genomes: the micrornas of brugia pahangi and haemonchus contortus are largely novel.micrornas (mirnas) play key roles in regulating post-transcriptional gene expression and are essential for development in the free-living nematode caenorhabditis elegans and in higher organisms. whether micrornas are involved in regulating developmental programs of parasitic nematodes is currently unknown. here we describe the the mirna repertoire of two important parasitic nematodes as an essential first step in addressing this question.201222216965
rapid detection and identification of brugia malayi, b. pahangi, and dirofilaria immitis by high-resolution melting assay.human lymphatic filariasis is caused by filarial worms such as brugia malayi for which the major reservoir is domestic cats. however, domestic cats or dogs also carry nonhuman filaria such as brugia pahangi and dirofilaria immitis. we have developed a single-tube, real-time pcr with a high-resolution melting (hrm) analysis assay for detection and identification of b. malayi, b. pahangi, and d. immitis in blood samples. the designated primer pair in the pcr can amplify a 114-bp region of mitochon ...201323199268
reactive oxygen species production and brugia pahangi survivorship in aedes polynesiensis with artificial wolbachia infection types.heterologous transinfection with the endosymbiotic bacterium wolbachia has been shown previously to induce pathogen interference phenotypes in mosquito hosts. here we examine an artificially infected strain of aedes polynesiensis, the primary vector of wuchereria bancrofti, which is the causative agent of lymphatic filariasis (lf) throughout much of the south pacific. embryonic microinjection was used to transfer the walbb infection from aedes albopictus into an aposymbiotic strain of ae. polyne ...201223236284
armigeres subalbatus incriminated as a vector of zoonotic brugia pahangi filariasis in suburban kuala lumpur, peninsular malaysia.in 2011, we reported occurrence of natural human infections with brugia pahangi, a filarial worm of dogs and cats, in a surburb of kuala lumpur, the capital city of malaysia. our preliminary entomological survey at that time suggested the mosquito species armigeres subalbatus as the vector of the zoonotic infections. in this present report, we provide biological evidence to confirm our preliminary finding.201323898840
brugia pahangi: immunization with early l3 es alters parasite migration, and reduces microfilaremia and lymphatic lesion formation in gerbils (meriones unguiculatus).previous studies have shown that intradermally (id) injected brugia pahangi l3 s migrate through various tissues and into the lymphatics of gerbils in a distinct pattern. excretory/secretory products (es) produced at the time of invasion of b. pahangi are likely to be important in this early migration phase of the parasite life cycle in their rodent host. hence, early l3 es was collected from 24h in vitro cultures of b. pahangi l3 larvae and used in immunization experiments to investigate the ef ...201323981910
rapid detection and identification of wuchereria bancrofti, brugia malayi, b. pahangi, and dirofilaria immitis in mosquito vectors and blood samples by high resolution melting real-time pcr.a simple, rapid, and high-throughput method for detection and identification of wuchereria bancrofti, brugia malayi, brugia pahangi, and dirofilaria immitis in mosquito vectors and blood samples was developed using a real-time pcr combined with high-resolution melting (hrm) analysis. amplicons of the 4 filarial species were generated from 5s rrna and spliced leader sequences by the real-time pcr and their melting temperatures were determined by the hrm method. melting of amplicons from w. bancro ...201324516268
successful treatment of brugia pahangi in naturally infected cats with ivermectin.lymphatic filariasis is a common parasitic disease of cats in tropical regions including thailand. the objective of this study was to determine the efficacy of ivermectin against microfilariae of brugia pahangi in naturally infected cats. eight cats naturally infected with b. pahangi were divided into control (untreated) and treated groups. cats in the latter group were given ivermectin injection at 400 µg/kg weekly for 2 months. microfilariae were counted every week until 48 weeks. microfilarem ...201324516287
vector and reservoir host of a case of human brugia pahangi infection in selangor, peninsular malaysia.a case of human eye infection caused by brugia pahangi was reported in 2010 in a semi rural village in selangor, peninsular malaysia. our report here reveals results of investigation on the vector and animal host for the transmission of the infection. we conducted entomological survey and cat blood examination in the vicinity of the patient's home. the mosquito species armigeres subalbatus was incriminated as the vector, whereas cat served as the reservoir host.201324522144
a repurposing strategy for hsp90 inhibitors demonstrates their potency against filarial nematodes.novel drugs are required for the elimination of infections caused by filarial worms, as most commonly used drugs largely target the microfilariae or first stage larvae of these infections. previous studies, conducted in vitro, have shown that inhibition of hsp90 kills adult brugia pahangi. as numerous small molecule inhibitors of hsp90 have been developed for use in cancer chemotherapy, we tested the activity of several novel hsp90 inhibitors in a fluorescence polarization assay and against micr ...201424551261
intraperitoneal development of the filarial nematode brugia malayi in the mongolian jird (meriones unguiculatus).in the present study, we describe intraperitoneal development of the fr3 strain of brugia malayi in mongolian jirds (meriones unguiculatus). the third molt for male worms occurred between 4 and 7 days postinfection (dpi) and between 4 and 8 dpi for females. the fourth and final molt occurred between days 21 and 29 for males and 25 and 34 for females, considerably earlier than the times reported for subcutaneous infection models using cats and jirds. the timing of the third molt coincided largely ...201424664084
nematode hsp90: highly conserved but functionally diverse.nematodes are amongst the most successful and abundant organisms on the planet with approximately 30 000 species described, although the actual number of species is estimated to be one million or more. despite sharing a relatively simple and invariant body plan, there is considerable diversity within the phylum. nematodes have evolved to colonize most ecological niches, and can be free-living or can parasitize plants or animals to the detriment of the host organism. in this review we consider th ...201424721950
filarial antigens mediate apoptosis of human monocytes through toll-like receptor 4.apoptosis of several host cells induced by parasites/parasite products has been investigated in human filariasis to understand immune hyporesponsiveness. however, apoptosis of monocytes-one of the major antigen presenting cells in peripheral circulation, which are chronically exposed to filarial antigens in infected subjects-is yet to be understood.201424737802
what does not kill them makes them stronger: larval environment and infectious dose alter mosquito potential to transmit filarial worms.for organisms with complex life cycles, larval environments can modify adult phenotypes. for mosquitoes and other vectors, when physiological impacts of stressors acting on larvae carry over into the adult stage they may interact with infectious dose of a vector-borne pathogen, producing a range of phenotypes for vector potential. investigation of impacts of a common source of stress, larval crowding and intraspecific competition, on adult vector interactions with pathogens may increase our unde ...024827444
detection of circulating parasite-derived micrornas in filarial infections.filarial nematodes cause chronic and profoundly debilitating diseases in both humans and animals. applications of novel technology are providing unprecedented opportunities to improve diagnosis and our understanding of the molecular basis for host-parasite interactions. as a first step, we investigated the presence of circulating mirnas released by filarial nematodes into the host bloodstream. mirna deep-sequencing combined with bioinformatics revealed over 200 mature mirna sequences of potentia ...201425033073
a novel member of the let-7 microrna family is associated with developmental transitions in filarial nematode parasites.filarial nematodes are important pathogens in the tropics transmitted to humans via the bite of blood sucking arthropod vectors. the molecular mechanisms underpinning survival and differentiation of these parasites following transmission are poorly understood. micrornas are small non-coding rna molecules that regulate target mrnas and we set out to investigate whether they play a role in the infection event.201525896062
loiasis in a japanese traveler returning from central africa.we encountered a probable case of loiasis in a returned traveler from central africa. a 52-year-old japanese woman presented to our hospital complaining of discomfort in her eyes and skin. she reported having frequently visited central africa over many years and having been extensively exposed to the rainforest climate and ecosystem. although no microfilariae were found in her blood, there was an elevated level of igg antibodies against the crude antigens of brugia pahangi, which have cross-reac ...201526161033
rapid differentiation of filariae in unstained and stained paraffin-embedded sections by a high-resolution melting analysis pcr assay.apart from infection with human filariae, zoonotic filariasis also occurs worldwide, and the numbers of cases have been increasing steadily. diagnosis of intact filariae in tissues or organs depends on histological identification. the morphology of parasites in tissue-embedded sections is poor and shows high levels of homoplasy. thus, the use of morphological characteristics in taxonomic studies is difficult and may not allow a specific diagnosis.201526273808
draft genome of brugia pahangi: high similarity between b. pahangi and b. malayi.efforts to completely eradicate lymphatic filariasis from human population may be challenged by the emergence of brugia pahangi as another zoonotic lymphatic filarial nematode. in this report, a genomic study was conducted to understand this species at molecular level.201526350613
prevalence of filarial parasites in domestic and stray cats in selangor state, malaysia.to determine the prevalence of the filarial parasites,ie.,brugia malayi, brugia, brugia pahangi(b. pahangi), dirofilaria immitisanddirofilaria repens (d. repens) in domestic and stray cats.201526433654
assessment of blood collection from the lateral saphenous vein for microfilaria counts in mongolian gerbils (meriones unguiculatus) infected with brugia pahangi.the nih guidelines for survival bleeding of mice and rats note that using the retroorbital plexus has a greater potential for complications than do other methods of blood collection and that this procedure should be performed on anesthetized animals. lateral saphenous vein puncture has a low potential for complications and can be performed without anesthesia. mongolian gerbils (meriones unguiculatus) are the preferred rodent model for filarial parasite research. to monitor microfilaria counts in ...026678366
yeast-based high-throughput screens to identify novel compounds active against brugia malayi.lymphatic filariasis is caused by the parasitic worms wuchereria bancrofti, brugia malayi or b. timori, which are transmitted via the bites from infected mosquitoes. once in the human body, the parasites develop into adult worms in the lymphatic vessels, causing severe damage and swelling of the affected tissues. according to the world health organization, over 1.2 billion people in 58 countries are at risk of contracting lymphatic filariasis. very few drugs are available to treat patients infec ...201626812604
pyrosequencing using sl and 5s rrna as molecular markers for identifying zoonotic filarial nematodes in blood samples and mosquitoes.lymphatic filariasis is principally caused by wuchereria bancrofti, and brugia malayi. the other two filarial nematode species, brugia pahangi and dirofilaria immitis, possibly cause human zoonotic diseases.201627008279
antifilarial and antibiotic activities of methanolic extracts of melaleuca cajuputi flowers.we evaluated the activity of methanolic extracts of melaleuca cajuputi flowers against the filarial worm brugia pahangi and its bacterial endosymbiont wolbachia. anti-wolbachia activity was measured in worms and in aedes albopictus aa23 cells by pcr, electron microscopy, and other biological assays. in particular, microfilarial release, worm motility, and viability were determined. m. cajuputi flower extracts were found to significantly reduce wolbachia endosymbionts in aa23 cells, wolbachia sur ...201627417081
attempts to image the early inflammatory response during infection with the lymphatic filarial nematode brugia pahangi in a mouse model.helminth parasites remain a major constraint upon human health and well-being in many parts of the world. treatment of these infections relies upon a very small number of therapeutics, most of which were originally developed for use in animal health. a lack of high throughput screening systems, together with limitations of available animal models, has restricted the development of novel chemotherapeutics. this is particularly so for filarial nematodes, which are long-lived parasites with a compl ...201627992545
chemoattractant activity of tris-(hydroxymethyl)aminomethane for brugia pahangi infective third-stage larvae.urocanic acid (uca) is known as a major chemoattractant for strongyloides stercoralis infective third-stage larvae (l3). since brugia pahangi is a skin-penetrating parasitic nematode similar to s. stercoralis, uca was expected to be a chemoattractant for b. pahangi l3. thus, the chemoattractant activity of uca for b. pahangi l3 was assessed. the chemotactic responses of b. pahangi l3 to uca or acetic acid (ch3cooh) dissolved in amine solutions were assessed using an agar-plate assay. a test solu ...201728735573
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