Mapping the risk of soil-transmitted helminthic infections in the Philippines

Background In order to increase the efficient allocation of soil-transmitted helminth (STH) disease control resources in the Philippines, we aimed to describe for the first time the spatial variation in the prevalence of A. lumbricoides, T. trichiura and hookworm across the country, quantify the association between the physical environment and spatial variation of STH infection and develop predictive risk maps for each infection. Methodology/Principal Findings Data on STH infection from 35,573 individuals across the country were geolocated at the barangay level and included in the analysis. The analysis was stratified geographically in two major regions: 1) Luzon and the Visayas and 2) Mindanao. Bayesian geostatistical models of STH prevalence were developed, including age and sex of individuals and environmental variables (rainfall, land surface temperature and distance to inland water bodies) as predictors, and diagnostic uncertainty was incorporated. The role of environmental variables was different between regions of the Philippines. This analysis revealed that while A. lumbricoides and T. trichiura infections were widespread and highly endemic, hookworm infections were more circumscribed to smaller foci in the Visayas and Mindanao. Conclusions/Significance This analysis revealed significant spatial variation in STH infection prevalence within provinces of the Philippines. This suggests that a spatially targeted approach to STH interventions, including mass drug administration, is warranted. When financially possible, additional STH surveys should be prioritized to high-risk areas identified by our study in Luzon.

Immunological Effects of Probiotic Bacteria in Prevention and Treatment of Allergic Diseases in Children

Epidemiological and experimental studies suggest that changes in gut microbial balance are associated with increases in the prevalence of allergic diseases. Probiotics are proposed to provide beneficial immunoregulatory signals which aid in oral tolerance achievement and alleviation of symptoms of allergic diseases. The present study evaluates both the immunological mechanisms of probiotics in infants with allergic diseases and their preventive aspect among infants prone to allergy. Furthermore, the purpose of the study was to characterise the immunological features of cord blood mononuclear cells (CBMCs) in infants at high genetic risk for allergy. GATA-3 expression (p = 0.03), interleukin (IL) -2(p = 0.026), and IL-5 (p = 0.013) secretion of stimulated CBMCs were higher in IgE-sensitized infants at age 2 than in non-allergic, non-sensitized infants. Lactobacillus GG (LGG) treatment increased secretion of IFN-γ by PBMCs in vitro in infants with cow s milk allergy (CMA) (p = 0.006) and in infants with IgE-associated eczema (p = 0.017), when compared to levels in the placebo group. A probiotic mixture, increased secretion of IL-4 by PBMCs in vitro in infants with CMA (p = 0.028), when compared with placebo-group levels. The LGG treatment induced higher plasma C-reactive protein (CRP) (p = 0.021) and IL-6 (p = 0.036) levels in infants with IgE-associated eczema than in the placebo group. The probiotic mixture induced higher plasma IL-10 levels in infants with eczema (p = 0.016). In the prevention study of allergic dis-eases, the infants receiving the probiotic mixture had higher plasma levels of CRP (p = 0.008), total IgA (p = 0.016), total IgE (p = 0.047), and IL-10 (p = 0.002) than did infants in the placebo group. Increased CRP level at age 6 months was associated with a decreased risk for eczema at age 2 not only in the infants who received probiotics but also in the placebo group (p = 0.034). In conclusion, the priming of the GATA-3 and IL-5 pathway can occur in utero, and a primary feature of T-cells predisposing to IgE-sensitization seems to directly favour Th2 deviation. LGG treatment induced increased plasma levels of CRP and IL-6 in infants with IgE-associated eczema, suggesting an activation of innate immu-nity. The probiotic mixture, when given to allergy-prone infants, induced inflammation, detected as increased plasma CRP levels, which at age 6 months was associated with decreased risk for eczema at age 2.The probiotic-induced response in allergy prone infants was characterized by their higher plasma IL-10, total IgE, and CRP levels, without induction of an allergen-specific IgE response. In this respect, the probiotics in infancy appear to induce protective immune profiles that are characteristic for chronic low-grade inflammation, a response resembling that of helminth-like infections.

Rihmamatolääkkeiden vaikutuskohteita. Betuliinin johdannaisia mahdollisiksi uusiksi yhdisteiksi

Jokisokeus eli onkosersiaasi on ihmisen loismatotauti, jota aiheuttaa Onchocerca volvulus -rihmamato. Tautia esiintyy trooppisilla alueilla Afrikassa ja Latinalaisessa Amerikassa. Tartunnan saaneita on noin 37 miljoonaa. Jokisokeus ilmenee iho- ja silmäoireina. Oireet johtuvat loisen nuorimmista muodoista eli mikrofilarioista. Jokisokeutta vastaan on käyty jakamalla lähinnä mikrofilarioihin tehoavaa ivermektiiniä. Tarvetta olisi lääkkeelle, joka tappaisi aikuiset madot tai steriloisi naaraat. Rokote olisi vielä parempi vaihtoehto. Antibiootit on uusi hoitokeino, sillä O. volvuluksella on elintärkeänä symbionttina Wolbachia-bakteeri. Doksisykliini tappaa vähintään 60 prosenttia aikuisista madoista ja steriloi naaraita, mutta kuuri kestää viikkoja. Yksi lupaava yhdiste on emodepsidi, jolla on loismatolääkkeille uusi vaikutusmekanismi. Rihmamatolääkkeiksi on testattu lukuisia yhdisteitä. Jotkut niistä inhiboivat entsyymejä, joilla madot kiertävät ihmisen immuunipuolustusta. Toiset häiritsevät neljä kertaa tapahtuvaa nahanvaihtoa. Hyvä lääkkeiden vaikutuskohde on loiselle välttämätön mutta puuttuu nisäkkäiltä. Betuliini on triterpeeni, jota on runsaasti koivun tuohessa. Betuliini ja monet sen johdannaiset ovat farmakologisesti aktiivisia yhdisteitä, joita tutkitaan etenkin syöpä- ja HIV-lääkkeiksi. Helsingin yliopiston lääkekemian ryhmä on syntetisoinut ja tutkinut lukuisia johdoksia. Jotkin niistä ovat lupaavia esimerkiksi Leishmania-alkueläimiin, Chlamydia pneumoniae -bakteeriin ja alfaviruksiin. Siksi yhdisteitä kannattaisi tutkia muihinkin taudinaiheuttajiin, kuten rihmamatoihin. Sekä Wolbachialla että C. pneumoniaella on sama lipidisynteesireitti, joka on kummallekin elintärkeä. Betuliinista syntetisoitiin johdoksia, joissa betuliinin alkoholeja on hapetettu karbonyyleiksi ja joihin on liitetty typpiheterorengas. Sekä Leishmania donovani että L. braziliensis -tutkimuksissa tehokkain oli formyylibetuliinin heterosykli. Vaikka valmistettuja yhdisteitä ei ole tutkittu rihmamatotesteissä, jatkossa voisi syntetisoida johdannaisia, joissa karbonyylien tilalla on typpirakenteita, koska C. pneumoniaehen hyvin tehonneessa yhdisteessä betuliinin OH-ryhmien tilalla on oksiimi.

A review of diseases associated with cage culture systems: diagnosis and control in smale scale fish farming

Fish cage culture is a rapid aquacultural practice of producing fish with more yield compared to traditional pond culture. Several species cultured by this method include Cyprinus carpio, Orechromis niloticus, Sarotherodon galilaeus, Tilapia zilli, Clarias lazera, C. gariepinus, Heterobranchus bidorsalis, Citharinus citharus, Distochodus rostratus and Alestes dentes. However, the culture of fish in cages has some problems that are due to mechanical defects of the cage or diseases due to infection. The mechanical problems which may lead to clogged net, toxicity and easy access by predators depend on defects associated with various types of nets which include fold sieve cloth net, wire net, polypropylene net, nylon, galvanized and welded net. The diseases problems are of two types namely introduced diseases due to parasites. The introduced parasites include Crustaseans, Ergasilus sp. Argulus africana, and Lamprolegna sp, Helminth, Diplostomulum tregnna: Protozoan, Trichodina sp, Myxosoma sp, Myxobolus sp. the second disease problems are inherent diseases aggravated by the very rich nutrient environment in cages for rapid bacterial, saprophytic fungi, and phytoplanktonic bloom resulting in clogging of net, stagnation of water and low biological oxygen demand (BOD). The consequence is fish kill, prevalence of gill rot and dropsy conditions. Recommendations on routine cage hygiene, diagnosis and control procedures to reduce fish mortality are highlighted

Estudo imunológico e histopatológico da infecção experimental por Schistosoma mansoni em camundongos geneticamente selecionados para tolerância oral

A esquistossomose acomete 207 milhões de pessoas, com mais de 200 mil mortes anuais. Seu principal agente etiológico é o helminto Schistosoma e o principal modelo experimental, o camundongo. Linhagens de camundongos selecionadas geneticamente para susceptibilidade (TS) e resistência (TR) a tolerância imunológica constituem bons modelos para o estudo da resposta imunológica específica e inespecífica nas infecções. O objetivo deste trabalho foi caracterizar a infecção experimental por S. mansoni nestes camundongos, evidenciando a imunopatologia por diversos parâmetros na fase aguda da infecção. TR e TS não diferiram quanto a penetração de cercárias, recuperação de vermes adultos, fecundidade/produtividade de ovos das fêmeas de S. mansoni, mas predominaram ovos mortos em TS. Quanto maior o número de casais, maior a probabilidade de troca de casais e regressão sexual da fêmea, além de pequena redução da produtividade de ovos. Análise ultraestrutural dos parasitos machos recuperados de TS apresentaram tubérculos edemaciados, espinhos encurtados e em menor densidade que os parasitos dos TR. O tegumento dos parasitos recuperados de TS apresentou-se desorganizado, intensamente vacuolizado e com tendência a se desprender da superfície e espinhos internalizados e células vitelínicas desorganizadas. TS desenvolveram granulomas hepáticos grandes, com fibras radiais e predomínio do estágio exsudativo-produtivo com características de fase produtiva (EP/P), enquanto camundongos TR desenvolveram granulomas menores, com fibras concêntricas e predomínio de granulomas exsudativo-produtivos. TS desenvolveu hepatomegalia mais acentuada na fase aguda da infecção e exacerbada esplenomegalia na fase crônica. A aspartato aminotransferase mais elevada nos TR foi coerente com a acentuada histólise nos granulomas iniciais dos TR. É possível que a histólise menor em TS tenha contribuído para sua intensa hepatomegalia na fase aguda. Leucócitos totais séricos aumentaram em TS, nas fases aguda e crônica, mas não em TR. TS apresentaram anemia durante a fase crônica da infecção, possivelmente devido ao desvio na hematopoiese medular para a produção de leucócitos ou apoptose das hemácias. A mieloperoxidase neutrofílica hepática e no íleo foi maior em TS e a peroxidase de eosinófilos foi mais elevada no íleo do TS. Ambas as linhagens produziram IFN-γ, mas os níveis funcionais de IFN-γ foram diferentes nas duas linhagens em cultura de células. É possível que a imunopatologia hepática grave na linhagem TS possa estar relacionada aos altos títulos IFN-γ. TS produziu IL-10 em maior quantidade, entretanto esta citocina não foi capaz de regular o crescimento exacerbado dos granulomas hepáticos. Altos títulos de IL-4 na linhagem TS também são coerentes com a exacerbação dos granulomas, pois, como a IL-13, a IL-4 induz síntese de colágeno e está relacionada ao desenvolvimento da fibrose no granuloma esquistossomótico. Observamos redução do percentual relativo de células T CD4+ hepáticas de animais infectados em ambas as linhagens e redução percentual nas subpopulações de linfócitos B na medula óssea (precursores, linfócitos B imaturos, maduros e plasmócitos) mais acentuada em TS que em TR, possivelmente devido a extensa mobilização de B imaturos induzida pela inflamação ou desvio da hematopoiese para síntese de granulócitos em TS. Quantitativamente, TR não alterou suas subpopulações de linfócitos B. TS e TR são bons modelos para estudo da resposta imunológica na infecção esquistossomótica experimental. Novos estudos são necessários para confirmar nossas propostas e compreender os mecanismos envolvidos na diferença da resposta imunológica dessas linhagens na relação schistosoma-hospedeiro.

Características morfológicas de vermes adultos de Schistosoma mansoni Sambon, 1907 recuperados de camundongos alimentados com dieta hiperlípidíca na fase crônica da infecção esquistossomótica. Análise por microscopia de campo claro e confocal

Estudos em animais experimentais evidenciaram associações significativas entre esquistossomose mansoni e hipercolesterolemia. Estudos in vitro e in vivo já demonstraram que o colesterol é essencial para Schistosoma mansoni, embora este não tenha capacidade de sintetizá-lo. A captação é realizada a partir do ambiente (cultivo ou hospedeiro) através do tegumento. O colesterol está envolvido nos mecanismos de evasão do helminto contra a resposta imunológica, além de poder participar na modulação da sinalização celular e reprodução, estimulando os órgãos reprodutores dos helmintos adultos como observado na fase aguda da infecção experimental. Este trabalho tem como objetivo avaliar se o mesmo fenômeno ocorre na fase crônica. Os helmintos foram recuperados de dez camundongos submetidos à dieta hiperlipídica ou padrão (controle) foram corados pelo carmin cloridrico e montados, individualmente, em lâmina histológica com bálsamo do Canadá. A preparação foi analisada por microscopia de campo claro nos seguintes caracteres: tegumento e o sistema reprodutor nos vermes machos (lobos testiculares, vesícula seminal, lobos testiculares supranumerários e canal ginecóforo) e, nas fêmeas (ovário, oótipo, útero, ovo, glândulas vitelínicas e espermateca). Posteriormente, algumas lâminas foram separadas para visualização pela microscopia confocal dos órgãos do sistema reprodutores acima descritos. Apesar de ter sido observado uma maior quantidade de espermatozoides, uma maior quantidade de oócitos sendo liberados no grupo da dieta, não houve diferença estatística significativa (p>0,05) entre os grupos analisados. Houve um aumento na oogênese como observado na fase aguda. Dessa forma, o colesterol pode estar relacionado com a estimulação na atividade dos órgãos reprodutores dos helmintos adultos na fase crônica da infecção.

DEVELOPMENT OF EUSTRONGYLIDES IGNOTUS (NEMATODA: DIOCTOPHMIDA) IN DOMESTIC DUCKS (ANAS PLATYRHYNCHOS DOMESTICA (L.))

Investigating the development of Eustrongylides ignotus in its definitive host would enable us to trace the complete life cycle of this nematode. Fourth-stage larvae isolated from naturally infected swamp eels (Monopterus albus) were used to infect domestic ducks (Anas platyrhynchos domestica [L.]). We observed that male and female worms exhibited different developmental patterns in host ducks. In males, the fourth molt occurred at day 1-2 post-infection (PI), after which they attained maturity on day 4 PI and died between day 7 and 9 PI. However, females underwent the fourth molt at day 2-4 PI, produced eggs from day 9 to 17 PI, and then degenerated and died. When compared 10 fourth-stage Female larvae, adult females demonstrated a considerable increase in total body size with a 151% increase in average body width and a 17% increase in average body length. However. the increase in size of the male larvae was not its significant as that in females. The average body width in adult males exhibited only a 45% increase over that in the larval stage.

Communities of gastrointestinal helminths of fish in historically connected habitats: habitat fragmentation effect in a carnivorous catfish Pelteobagrus fulvidraco from seven lakes in flood plain of the Yangtze River, China

Background: Habitat fragmentation may result in the reduction of diversity of parasite communities by affecting population size and dispersal pattern of species. In the flood plain of the Yangtze River in China, many lakes, which were once connected with the river, have become isolated since the 1950s from the river by the construction of dams and sluices, with many larger lakes subdivided into smaller ones by road embankments. These artificial barriers have inevitably obstructed the migration of fish between the river and lakes and also among lakes. In this study, the gastrointestinal helminth communities were investigated in a carnivorous fish, the yellowhead catfish Pelteobagrus fulvidraco, from two connected and five isolated lakes in the flood plain in order to detect the effect of lake fragmentation on the parasite communities. Results: A total of 11 species of helminths were recorded in the stomach and intestine of P. fulvidraco from seven lakes, including two lakes connected with the Yangtze River, i.e. Poyang and Dongting lakes, and five isolated lakes, i.e. Honghu, Liangzi, Tangxun, Niushan and Baoan lakes. Mean helminth individuals and diversity of helminth communities in Honghu and Dongting lakes was lower than in the other five lakes. The nematode Procamallanus fulvidraconis was the dominant species of communities in all the seven lakes. No significant difference in the Shannon-Wiener index was detected between connected lakes (0.48) and isolated lakes (0.50). The similarity of helminth communities between Niushan and Baoan lakes was the highest (0.6708), and the lowest was between Tangxun and Dongting lakes (0.1807). The similarity was low between Dongting and the other lakes, and the similarity decreased with the geographic distance among these lakes. The helminth community in one connected lake, Poyang Lake was clustered with isolated lakes, but the community in Dongting Lake was separated in the tree. Conclusion: The similarity in the helminth communities of this fish in the flood-plain lakes may be attributed to the historical connection of these habitats and to the completion of the life-cycles of this fish as well as the helminth species within the investigated habitats. The diversity and the digenean majority in the helminth communities can be related to the diet of this fish, and to the lacustrine and macrophytic characters of the habitats. The lake isolation from the river had little detectable effect on the helminth communities of the catfish in flood-plain lakes of the Yangtze River. The low similarities in helminth communities between the Dongting Lake and others may just be a reflection of its unique water environment and anthropogenic alterations or fragmentation in this lake.

Identification and characterization of a cathepsin L-like cysteine protease from Taenia solium metacestode

Taenia solium metacestode, a larval pork tapeworm, is a causative agent of neurocysticercosis, one of the most common parasitic diseases in the human central nervous system. In this study, we identified a cDNA encoding for a cathepsin L-like cysteine protease from the T solium metacestode (TsCL-1) and characterized the biochemical properties of the recombinant enzyme. The cloned cDNA of 1216 bp encoded 339 amino acids with an approximate molecular weight of 37.6 kDa which containing a typical signal peptide sequence (17 amino acids), a pro-domain (106 amino acids), and a mature domain (216 amino acids). Sequence alignments of TsCL-1 showed low sequence similarity of 27.3-44.6 to cathepsin L-like cysteine proteases from other helminth parasites, but the similarity was increased to 35.9-55.0 when compared to mature domains. The bacterially expressed recombinant protein (rTsCL-1) did not show enzyme activity; however, the rTsCL-1 expressed in Pichia pastoris showed typical biochemical characteristics of cysteine proteases. It degraded human immunoglobulin G (IgG) and bovine serum albumin (BSA), but not collagen. Western blot analysis of the rTsCL-1 showed antigenicity against the sera from patients with cysticercosis, sparganosis or fascioliasis, but weak or no antigenicity against the sera from patients with paragonimiasis or clonorchiasis. (c) 2006 Published by Elsevier B.V.

Pol II docking and pausing at growth and stress genes in C. elegans.

Fluctuations in nutrient availability profoundly impact gene expression. Previous work revealed postrecruitment regulation of RNA polymerase II (Pol II) during starvation and recovery in Caenorhabditis elegans, suggesting that promoter-proximal pausing promotes rapid response to feeding. To test this hypothesis, we measured Pol II elongation genome wide by two complementary approaches and analyzed elongation in conjunction with Pol II binding and expression. We confirmed bona fide pausing during starvation and also discovered Pol II docking. Pausing occurs at active stress-response genes that become downregulated in response to feeding. In contrast, "docked" Pol II accumulates without initiating upstream of inactive growth genes that become rapidly upregulated upon feeding. Beyond differences in function and expression, these two sets of genes have different core promoter motifs, suggesting alternative transcriptional machinery. Our work suggests that growth and stress genes are both regulated postrecruitment during starvation but at initiation and elongation, respectively, coordinating gene expression with nutrient availability.

A possible model of benzimidazole binding to beta-tubulin disclosed by invoking an inter-domain movement.

Although it is well established that benzimidazole (BZMs) compounds exert their therapeutic effects through binding to helminth beta-tubulin and thus disrupting microtubule-based processes in the parasites, the precise location of the benzimidazole-binding site on the beta-tubulin molecule has yet to be determined. In the present study, we have used previous experimental data as cues to help identify this site. Firstly, benzimidazole resistance has been correlated with a phenylalanine-to-tyrosine substitution at position 200 of Haemonchus contortus beta-tubulin isotype-I. Secondly, site-directed mutagenesis studies, using fungi, have shown that other residues in this region of the protein can influence the interaction of benzimidazoles with beta-tubulin. However, the atomic structure of the alphabeta-tubulin dimer shows that residue 200 and the other implicated residues are buried within the protein. This poses the question: how might benzimidazoles interact with these apparently inaccessible residues? In the present study, we present a mechanism by which those residues generally believed to interact with benzimidazoles may become accessible to the drugs. Furthermore, by docking albendazole-sulphoxide into a modelled H. contortus beta-tubulin molecule we offer a structural explanation for how the mutation conferring benzimidazole resistance in nematodes may act, as well as a possible explanation for the species-specificity of benzimidazole anthelmintics.

Cathepsin L1, the major protease involved in liver fluke (Fasciola hepatica) virulence.

The secretion and activation of the major cathepsin L1 cysteine protease involved in the virulence of the helminth pathogen Fasciola hepatica was investigated. Only the fully processed and active mature enzyme can be detected in medium in which adult F. hepatica are cultured. However, immunocytochemical studies revealed that the inactive procathepsin L1 is packaged in secretory vesicles of epithelial cells that line the parasite gut. These observations suggest that processing and activation of procathepsin L1 occurs following secretion from these cells into the acidic gut lumen. Expression of the 37-kDa procathepsin L1 in Pichia pastoris showed that an intermolecular processing event within a conserved GXNXFXD motif in the propeptide generates an active 30-kDa intermediate form. Further activation of the enzyme was initiated by decreasing the pH to 5.0 and involved the progressive processing of the 37 and 30-kDa forms to other intermediates and finally to a fully mature 24.5 kDa cathepsin L with an additional 1 or 2 amino acids. An active site mutant procathepsin L, constructed by replacing the Cys26 with Gly26, failed to autoprocess. However, [Gly26]procathepsin L was processed by exogenous wild-type cathepsin L to a mature enzyme plus 10 amino acids attached to the N terminus. This exogenous processing occurred without the formation of a 30-kDa intermediate form. The results indicate that activation of procathepsin L1 by removal of the propeptide can occur by different pathways, and that this takes place within the parasite gut where the protease functions in food digestion and from where it is liberated as an active enzyme for additional extracorporeal roles.

Neuropeptide signalling: a repository of targets for novel endectocides?

The only available parasiticides with a spectrum of action that includes a broad range of helminth and arthropod parasites are the macrocyclic lactones. Designated endectocides, these drugs have action against both endoparasitic nematodes and ectoparasitic arthropods. Unfortunately, the discovery of such drugs is exceedingly rare and there is no evidence that novel endectocidal agents will be identified and developed in the short to medium term. However, the discovery of neuropeptides with motor-modulatory activities in both arthropods and helminths, coupled with recent progress in the characterization of invertebrate neuropeptide receptors, has the potential to propel neuropeptide signalling to the forefront of efforts to develop a novel endectocide.

Discovery of multiple neuropeptide families in the phylum Platyhelminthes

Available evidence shows that short amidated neuropeptides are widespread and have important functions within the nervous systems of all flatworms (phylum Platyhelminthes) examined, and could therefore represent a starting point for new lead drug compounds with which to combat parasitic helminth infections. However, only a handful of these peptides have been characterised, the rigorous exploration of the flatworm peptide signalling repertoire having been hindered by the dearth of flatworm genomic data. Through searches of both expressed sequence tags and genomic resources using the basic local alignment search tool (BLAST), we describe 96 neuropeptides on 60 precursors from 10 flatworm species. Most of these (51 predicted peptides on 14 precursors) are novel and are apparently restricted to flatworms; the remainder comprise nine recognised peptide families including FMRFamide-like (FLPs), neuropeptide F (NPF)-like, myomodulin-like, buccalin-like and neuropeptide FF (NPFF)-like peptides; notably, the latter have only previously been reported in vertebrates. Selected peptides were localised immunocytochemically to the Schistosoma mansoni nervous system. We also describe several novel flatworm NPFs with structural features characteristic of the vertebrate neuropeptide Y (NPY) superfamily, previously unreported characteristics which support the common ancestry of flatworm NPFs with the NPY-superfamily. Our dataset provides a springboard for investigation of the functional biology and therapeutic potential of neuropeptides in flatworms, simultaneously launching flatworm neurobiology into the post-genomic era. (C) 2009 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Microtubules as antiparasitic drug targets

Background: Parasitic diseases including malaria, leishmaniasis and schistosomiasis take a terrible toll of human life, health and productivity, especially in tropical and subtropical regions, and are also highly significant in animal health worldwide. Antiparasitic drugs are the mainstays of control of most of these diseases, but in many cases current therapies are inadequate and in some the situation is deteriorating because of drug resistance. Microtubules, as essential components of almost all eukaryotic cells, are proven drug targets in many helminth diseases and show promise as targets for the development of new antiprotozoal drugs. Objective: This article reviews the chemistry of the microtubule inhibitors in current use and under investigation as antiparasitic agents, their activities against the major parasites and their mechanisms of action. New directions in both inhibitor chemistry and biological evaluation are discussed. Conclusions: The most promising immediate avenues for discovery and design appear to lie in development of novel benzimidazoles for helminth parasites and compounds based on antimitotic herbicides for protozoal parasites. New understanding from functional genomics, structural biology and microtubular imaging will help accelerate the development of completely novel antiparasitic drugs targeting microtubules.