Showing papers in "Parasitology in 2009"
TL;DR: A review of the transmission and control of ZVL can be found in this article, which highlights the lack of randomized controlled trials of both dog culling and residual insecticide spraying.
Abstract: Zoonotic visceral leishmaniasis (ZVL) caused by Leishmania infantum is an important disease of humans and dogs. Here we review aspects of the transmission and control of ZVL. Whilst there is clear evidence that ZVL is maintained by sandfly transmission, transmission may also occur by non-sandfly routes, such as congenital and sexual transmission. Dogs are the only confirmed primary reservoir of infection. Meta-analysis of dog studies confirms that infectiousness is higher in symptomatic infection; infectiousness is also higher in European than South American studies. A high prevalence of infection has been reported from an increasing number of domestic and wild mammals; updated host ranges are provided. The crab-eating fox Cerdocyon thous, opossums Didelphis spp., domestic cat Felis cattus, black rat Rattus rattus and humans can infect sandflies, but confirmation of these hosts as primary or secondary reservoirs requires further xenodiagnosis studies at the population level. Thus the putative sylvatic reservoir(s) of ZVL remains unknown. Review of intervention studies examining the effectiveness of current control methods highlights the lack of randomized controlled trials of both dog culling and residual insecticide spraying. Topical insecticides (deltamethrin-impregnated collars and pour-ons) have been shown to provide a high level of individual protection to treated dogs, but further community-level studies are needed.
402 citations
TL;DR: It is concluded that, for achieving integrated and sustainable control of neglected tropical diseases, a set of interventions must be tailored to a given endemic setting and fine-tuned over time in response to the changing nature and impact of control.
Abstract: In May 2001, the World Health Assembly (WHA) passed a resolution which urged member states to attain, by 2010, a minimum target of regularly administering anthelminthic drugs to at least 75% and up to 100% of all school-aged children at risk of morbidity. The refined global strategy for the prevention and control of schistosomiasis and soil-transmitted helminthiasis was issued in the following year and large-scale administration of anthelminthic drugs endorsed as the central feature. This strategy has subsequently been termed 'preventive chemotherapy'. Clearly, the 2001 WHA resolution led the way for concurrently controlling multiple neglected tropical diseases. In this paper, we recall the schistosomiasis situation in Africa in mid-2003. Adhering to strategic guidelines issued by the World Health Organization, we estimate the projected annual treatment needs with praziquantel among the school-aged population and critically discuss these estimates. The important role of geospatial tools for disease risk mapping, surveillance and predictions for resource allocation is emphasised. We clarify that schistosomiasis is only one of many neglected tropical diseases and that considerable uncertainties remain regarding global burden estimates. We examine new control initiatives targeting schistosomiasis and other tropical diseases that are often neglected. The prospect and challenges of integrated control are discussed and the need for combining biomedical, educational and engineering strategies and geospatial tools for sustainable disease control are highlighted. We conclude that, for achieving integrated and sustainable control of neglected tropical diseases, a set of interventions must be tailored to a given endemic setting and fine-tuned over time in response to the changing nature and impact of control. Consequently, besides the environment, the prevailing demographic, health and social systems contexts need to be considered.
374 citations
TL;DR: The case for the control of schistosomiasis has been strengthened by research by SCI teams and the principle that a national programme using ‘preventive chemotherapy’ can be successfully implemented in sub-Saharan Africa, whenever the resources are available.
Abstract: Schistosomiasis remains one of the most prevalent parasitic diseases in developing countries. After malaria, schistosomiasis is the most important tropical disease in terms of human morbidity with significant economic and public health consequences. Although schistosomiasis has recently attracted increased focus and funding for control, it has been estimated that less than 20% of the funding needed to control the disease in Africa is currently available. In this article the following issues are discussed: the rationale, development and objectives of the Schistosomiasis Control Initiative (SCI)-supported programmes; the management approaches followed to achieve implementation by each country; mapping, monitoring and evaluation activities with quantifiable impact of control programmes; monitoring for any potential drug resistance; and finally exit strategies within each country. The results have demonstrated that morbidity due to schistosomiasis has been reduced by the control programmes. While challenges remain, the case for the control of schistosomiasis has been strengthened by research by SCI teams and the principle that a national programme using 'preventive chemotherapy' can be successfully implemented in sub-Saharan Africa, whenever the resources are available. SCI and partners are now actively striving to raise further funds to expand the coverage of integrated control of neglected tropical diseases (NTDs) in sub-Saharan Africa.
292 citations
TL;DR: The profound impact of this parallel research on genetic diversity of T. cruzi and Leishmania is described, in the context of epidemiology, taxonomy and disease control.
Abstract: Trypanosoma cruzi is the protozoan agent of Chagas disease, and the most important parasitic disease in Latin America. Protozoa of the genus Leishmania are global agents of visceral and cutaneous leishmaniasis, fatal and disfiguring diseases. In the 1970s multilocus enzyme electrophoresis demonstrated that T. cruzi is a heterogeneous complex. Six zymodemes were described, corresponding with currently recognized lineages, TcI and TcIIa-e--now defined by multiple genetic markers. Molecular epidemiology has substantially resolved the phylogeography and ecological niches of the T. cruzi lineages. Genetic hybridization has fundamentally influenced T. cruzi evolution and epidemiology of Chagas disease. Genetic exchange of T. cruzi in vitro involves fusion of diploids and genome erosion, producing aneuploid hybrids. Transgenic fluorescent clones are new tools to elucidate molecular genetics and phenotypic variation. We speculate that pericardial sequestration plays a role in pathogenesis. Multilocus sequence typing, microsatellites and, ultimately, comparative genomics are improving understanding of T. cruzi population genetics. Similarly, in Leishmania, genetic groups have been defined, including epidemiologically important hybrids; genetic exchange can occur in the sand fly vector. We describe the profound impact of this parallel research on genetic diversity of T. cruzi and Leishmania, in the context of epidemiology, taxonomy and disease control.
216 citations
TL;DR: The findings indicate that the complexity of T. cruzi is larger than currently known, and confirmed bats as important reservoirs and potential source of T.'s cruzi infections to humans.
Abstract: We characterized 15 Trypanosoma cruzi isolates from bats captured in the Amazon, Central and Southeast Brazilian regions. Phylogenetic relationships among T. cruzi lineages using SSU rDNA, cytochrome b, and Histone H2B genes positioned all Amazonian isolates into T. cruzi I (TCI). However, bat isolates from the other regions, which had been genotyped as T. cruzi II (TC II) by the traditional genotyping method based on mini-exon gene employed in this study, were not nested within any of the previously defined TCII sublineages, constituting a new genotype designated as TCbat. Phylogenetic analyses demonstrated that TCbat indeed belongs to T. cruzi and not to other closely related bat trypanosomes of the subgenus Schizotrypanum, and that although separated by large genetic distances TCbat is closest to lineage TCI. A genotyping method targeting ITS1 rDNA distinguished TCbat from established T. cruzi lineages, and from other Schizotrypanum species. In experimentally infected mice, TCbat lacked virulence and yielded low parasitaemias. Isolates of TCbat presented distinctive morphological features and behaviour in triatomines. To date, TCbat genotype was found only in bats from anthropic environments of Central and Southeast Brazil. Our findings indicate that the complexity of T. cruzi is larger than currently known, and confirmed bats as important reservoirs and potential source of T. cruzi infections to humans.
214 citations
TL;DR: Treatment with praziquantel (PZQ) has become virtually the sole basis of schistosomiasis control in sub-Saharan Africa and elsewhere, and the drug is reviewed here in the context of the increasing rate that it is being used for this purpose.
Abstract: Treatment with praziquantel (PZQ) has become virtually the sole basis of schistosomiasis control in sub-Saharan Africa and elsewhere, and the drug is reviewed here in the context of the increasing rate that it is being used for this purpose. Attention is drawn to our relative lack of knowledge about the mechanisms of action of PZQ at the molecular level, the need for more work to be done on schistosome isolates that have been collected recently from endemic areas rather than those maintained in laboratory conditions for long periods, and our reliance for experimental work mainly on Schistosoma mansoni, little work having been done on S. haematobium. There is no evidence that resistance to PZQ has been induced in African schistosomes as a result of its large-scale use on that continent to date, but there is also no assurance that PZQ and/or schistosomes are in any way unique and that resistant organisms will not be selected as a result of widespread drug usage. The failure of PZQ to produce complete cures in populations given a routine treatment should therefore solicit considerable concern. With few alternatives to PZQ currently available and/or on the horizon, methods to monitor drug-susceptibility in African schistosomes need to be devised and used to help ensure that this drug remains effective for as long a time as possible.
184 citations
TL;DR: It is suggested that mtDNA should not be used as the sole source of markers in future studies where the goal is to reconstruct a phylogeny that does not only reflect a maternal lineage, but aims to describe the evolutionary history at species level or higher.
Abstract: The taxonomic status of Echinococcus, an important zoonotic cestode genus, has remained controversial, despite numerous attempts to revise it. Although mitochondrial DNA (mtDNA) has been the source of markers of choice for reconstructing the phylogeny of the genus, results derived from mtDNA have led to significant inconsistencies with earlier species classifications based on phenotypic analysis. Here, we used nuclear DNA markers to test the phylogenic relationships of members of the genus Echinococcus. The analysis of sequence data for 5 nuclear genes revealed a significantly different phylogeny for Echinococcus from that proposed on the basis of mitochondrial DNA sequence data, but was in agreement with earlier species classifications. The most notable results from the nuclear phylogeny were (1) E. multilocularis was placed as basal taxon, (2) all genotypes of Echinococcus granulosus grouped as a monophyletic entity, and (3) genotypes G8 and G10 clustered together. We conclude that the analysis of nuclear DNA data provides a more reliable means of inferring phylogenetic relationships within Echinococcus than mtDNA and suggest that mtDNA should not be used as the sole source of markers in future studies where the goal is to reconstruct a phylogeny that does not only reflect a maternal lineage, but aims to describe the evolutionary history at species level or higher.
152 citations
TL;DR: It is likely that reliance upon live, attenuated vaccines will increase in years to come after the commercial introduction of the first live attenuated vaccine, Paracox®, that has now been in use for 20 years.
Abstract: Eimeria spp. are the causative agents of coccidiosis, a major disease affecting many intensively-reared livestock, especially poultry. The chicken is host to 7 species of Eimeria that develop within intestinal epithelial cells and produce varying degrees of morbidity and mortality. Control of coccidiosis by the poultry industry is dominated by prophylactic chemotherapy but drug resistance is a serious problem. Strongly protective but species-specific immunity can be induced in chickens by infection with any of the Eimeria spp. At the Institute of Animal Health in Houghton, UK in the 1980s we showed that all 7 Eimeria spp. could be stably attenuated by serial passage in chickens of the earliest oocysts produced (i.e. the first parasites to complete their endogenous development) and this process resulted in the depletion of asexual development. Despite being highly attenuated, the precocious lines retained their immunizing capacity. Subsequent work led to the commercial introduction of the first live attenuated vaccine, Paracox®, that has now been in use for 20 years. As much work still remains to be done before the development of recombinant vaccines becomes a reality, it is likely that reliance upon live, attenuated vaccines will increase in years to come.
143 citations
TL;DR: Progress made with mapping schistosomiasis across Africa using available epidemiological data and, more recently, climate-based risk prediction is reviewed, and future directions for an integrated rapid mapping approach targeting multiple NTDs simultaneously are outlined, including potential challenges in developing an integrated survey tool.
Abstract: There is growing interest and commitment to the control of schistosomiasis and other so-called neglected tropical diseases (NTDs). Resources for control are inevitably limited, necessitating assessment methods that can rapidly and accurately identify and map high-risk communities so that interventions can be targeted in a spatially-explicit and cost-effective manner. Here, we review progress made with (1) mapping schistosomiasis across Africa using available epidemiological data and, more recently, climate-based risk prediction; (2) the development and use of morbidity questionnaires for rapid identification of high-risk communities of urinary schistosomiasis; and (3) innovative sampling-based approaches for intestinal schistosomiasis, using the lot quality assurance sampling technique. Experiences are also presented for the rapid mapping of other NTDs, including onchocerciasis, loiasis and lymphatic filariasis. Future directions for an integrated rapid mapping approach targeting multiple NTDs simultaneously are outlined, including potential challenges in developing an integrated survey tool. The lessons from the mapping of human helminth infections may also be relevant for the rapid mapping of malaria as its control efforts are intensified.
138 citations
TL;DR: It is argued that greater research effort and focus are needed to improve understanding of this neglected tropical disease, and the inappropriateness of relying solely on data concerning the much more extensively studied intestinal form of schistosomiasis caused by S. haematobium is highlighted.
Abstract: This review considers the current status of urinary schistosomiasis, caused by infection with Schistosoma haematobium, and argues that greater research effort and focus are needed to improve understanding of this neglected tropical disease (NTD). The inappropriateness of relying solely on data concerning the much more extensively studied intestinal form of schistosomiasis caused by S. mansoni is highlighted. The current lack of genome and transcriptome information for S. haematobium is directly hindering further targeted research and must be quickly rectified. Recent molecular phylogenies caution the expectation of similarities between schistosome species and highlight the close relationships of species within the S. haematobium group. Treatment, current and prospective drugs and vaccines, together with diagnosis are considered, highlighting the differences associated with urinary schistosomiasis. This infection has a significant and specific impact on the urino-genital system and has a strong association with bladder cancer, leading to severe and chronic morbidity. There is a clear need for new clinical initiatives in this area to better quantify the disease burden. Furthermore, emerging associations with HIV and other pathogens need to be closely monitored. Research is urgently needed to improve current knowledge in order to develop the next generation of control tools.
134 citations
TL;DR: Understanding the structure of MSP1 will help design and engineer better antigens that are more effective than the first generation of vaccine candidates, because a better understanding will highlight the limitations of current assays and identify the improvements required.
Abstract: Over the last 30 years, evidence has been gathered suggesting that merozoite surface protein 1 (MSP1) is a target of protective immunity against malaria. In a variety of experimental approaches using in vitro methodology, animal models and sero-epidemiological techniques, the importance of antibody against MSP1 has been established but we are still finding out what are the mechanisms involved. Now that clinical trials of MSP1 vaccines are underway and the early results have been disappointing, it is increasingly clear that we need to know more about the mechanisms of immunity, because a better understanding will highlight the limitations of our current assays and identify the improvements required. Understanding the structure of MSP1 will help us design and engineer better antigens that are more effective than the first generation of vaccine candidates. This review is focused on the carboxy-terminus of MSP1.
TL;DR: The concordance between real-time PCR and pyrosequencing results carried out in different laboratories indicated that these tools are suitable for the routine diagnosis of BZ-resistance in H. contortus.
Abstract: Benzimidazoles (BZ) are widely used to treat parasitic nematode infections of humans and animals, but resistance is widespread in veterinary parasites. Several polymorphisms in beta-tubulin genes have been associated with BZ-resistance. In the present study, we investigated beta-tubulin isotype 1 sequences of 18 Haemonchus contortus isolates with varying levels of resistance to thiabendazole. The only polymorphism whose frequency was significantly increased in the resistant isolates was TTC to TAC at codon 200. Real-time PCR (using DNA from 100 third-stage larvae, L3s) and pyrosequencing (from DNA from 1000-10 000 L3s) were used to measure allele frequencies at codon 200 of these isolates, producing similar results; drug sensitivity decreased with increasing TAC frequency. Pyrosequencing was also used to measure allele frequencies at positions 167 and 198. We showed that such measurements are sufficient to assess the BZ-resistance status of most H. contortus isolates. The concordance between real-time PCR and pyrosequencing results carried out in different laboratories indicated that these tools are suitable for the routine diagnosis of BZ-resistance in H. contortus. The molecular methods were more sensitive than the 'egg hatch test', and less time-consuming than current in vivo- or in vitro-anthelmintic resistance detection methods. Thus, they provide a realistic option for routine molecular resistance testing on farms.
TL;DR: Using a novel species-specific PCR based on the TPI gene, mixed infections with both assemblage A and B were detected in a large number of human patients, which might have important epidemiological implications.
Abstract: Stool samples from Belgian patients suffering from abdominal pain and/or diarrhoea were examined for Cryptosporidium and Giardia. Cryptosporidium-positive samples were genotyped using the 70 kDa heat shock protein and the 60 kDa glycoprotein (GP60) genes: C. hominis was identified in 54.2% and C. parvum in 45.8% of the samples. Sequencing at the GP60 locus indicated that subgenotype IbA10G2 of C. hominis and subgenotype IIaA15G2R1 of C. parvum were the most prevalent, although several other subgenotypes were identified. For Giardia, sequencing at the beta-giardin, triose phosphate isomerase (TPI) and glutamate dehydrogenase (GDH) genes revealed assemblage B as the most prevalent (74.4%) in human patients. A high degree of heterogeneity was found, especially on the beta-giardin gene, and to a lesser extent on the GDH gene. Furthermore, using a novel species-specific PCR based on the TPI gene, mixed infections with both assemblage A and B were detected in a large number (32.4%) of human patients, which might have important epidemiological implications.
TL;DR: Working definitions of RS, GIS and spatial analysis are given, and applications made to date with RS and GIS for the epidemiology and ecology of schistosomiasis in Africa are summarised.
Abstract: Beginning in 1970, the potential of remote sensing (RS) techniques, coupled with geographical information systems (GIS), to improve our understanding of the epidemiology and control of schistosomiasis in Africa, has steadily grown. In our current review, working definitions of RS, GIS and spatial analysis are given, and applications made to date with RS and GIS for the epidemiology and ecology of schistosomiasis in Africa are summarised. Progress has been made in mapping the prevalence of infection in humans and the distribution of intermediate host snails. More recently, Bayesian geostatistical modelling approaches have been utilized for predicting the prevalence and intensity of infection at different scales. However, a number of challenges remain; hence new research is needed to overcome these limitations. First, greater spatial and temporal resolution seems important to improve risk mapping and understanding of transmission dynamics at the local scale. Second, more realistic risk profiling can be achieved by taking into account information on people's socio-economic status; furthermore, future efforts should incorporate data on domestic access to clean water and adequate sanitation, as well as behavioural and educational issues. Third, high-quality data on intermediate host snail distribution should facilitate validation of infection risk maps and modelling transmission dynamics. Finally, more emphasis should be placed on risk mapping and prediction of multiple species parasitic infections in an effort to integrate disease risk mapping and to enhance the cost-effectiveness of their control.
TL;DR: The data suggest that breeding from infected ewes increases the risk of subsequent abortion and infection in lambs, and vertical transmission may be much more important than previously thought.
Abstract: Toxoplasma gondii is a highly ubiquitous and prevalent parasite. Despite the cat being the only definitive host, it is found in almost all geographical areas and warm blooded animals. Three routes of transmission are recognised: ingestion of oocysts shed by the cat, carnivory and congenital transmission. In natural populations, it is difficult to establish the relative importance of these routes. This paper reviews recent work in our laboratory which suggests that congenital transmission may be much more important than previously thought. Using PCR detection of the parasite, studies in sheep show that congenital transmission may occur in as many as 66% of pregnancies. Furthermore, in families of sheep on the same farm, exposed to the same sources of oocysts, significant divergent prevalences of Toxoplasma infection and abortion are found between different families. The data suggest that breeding from infected ewes increases the risk of subsequent abortion and infection in lambs. Congenital transmission rates in a natural population of mice were found to be 75%. Interestingly, congenital transmission rates in humans were measured at 19.8%. The results presented in these studies differ from those of other published studies and suggest that vertical transmission may be much more important than previously thought.
TL;DR: This review considers firstly the frequency with which exogenous and endogenous transmission occur, secondly the role of the immune response in controlling N. caninum infection and thirdly how the parasite persists in an immune-competent host and is re-activated during pregnancy.
Abstract: Vertical transmission of the protozoan parasite, Neospora caninum is highly efficient and can take two forms - endogenous transplacental transmission resulting from activation of the quiescent bradyzoite stage during pregnancy or exogenous transplacental transmission resulting from ingestion of oocysts during pregnancy. Calves born carrying infection derived from either endogenous or exogenous transplacental transmission are capable of infecting their offspring when they start to breed. This review considers firstly the frequency with which exogenous and endogenous transmission occur, secondly the role of the immune response in controlling N. caninum infection and thirdly how the parasite persists in an immune-competent host and is re-activated during pregnancy.
TL;DR: Rodents are shared intermediate or paratenic hosts for Echinococcus multilocularis, Toxocara spp.
Abstract: Rodents are shared intermediate or paratenic hosts for Echinococcus multilocularis, Toxocara spp. and Toxoplasma gondii, and may serve as valuable indicators for assessing the occurrence and the level of environmental contamination and infection pressure with free-living stages of these zoonotic parasites. We investigated 658 non-commensal rodents for parasite infections in the canton of Geneva, Switzerland. The prevalence of infection with E. multilocularis was highest in Arvicola terrestris captured in the north-western area (16.5%, CI: 10.1%-24.8%), possibly reflecting a higher red fox density due to the low incidence of sarcoptic mange in this part of the canton. The exposure rate to Toxocara spp. was highest in the urban area (13.2%, CI: 7.9%-20.3%), and may account for higher densities of domestic carnivore and red fox definitive hosts within the city. Exposure to T. gondii was widespread (5.0%, CI: 3.2-7.4%), indicating a ubiquitous distribution of infected cat definitive hosts. Interestingly, a widespread distribution of Taenia taeniaeformis, a parasite mainly transmitted by cats, was similarly evidenced in A. terrestris. Distinct spatial patterns for the different zoonotic parasites likely reflected differences in distribution, abundance, and habitat use of the respective definitive hosts. These results highlight the potential value of rodents as shared indicators for these pathogens.
TL;DR: The range of immunomodulatory molecules in selected parasitic trematodes, cestodes and nematodes, their impact on the immune cells in the host and how the host may recognize these molecules are illustrated.
Abstract: Infection with parasitic helminths takes a heavy toll on the health and well-being of humans and their domestic livestock, concomitantly resulting in major economic losses. Analyses have consistently revealed bioactive molecules in extracts of helminths or in their excretory/secretory products that modulate the immune response of the host. It is our view that parasitic helminths are an untapped source of immunomodulatory substances that, in pure form, could become new drugs (or models for drug design) to treat disease. Here, we illustrate the range of immunomodulatory molecules in selected parasitic trematodes, cestodes and nematodes, their impact on the immune cells in the host and how the host may recognize these molecules. There are many examples of the partial characterization of helminth-derived immunomodulatory molecules, but these have not yet translated into new drugs, reflecting the difficulty of isolating and fully characterizing proteins, glycoproteins and lipid-based molecules from small amounts of parasite material. However, this should not deter the investigator, since analytical techniques are now being used to accrue considerable structural information on parasite-derived molecules, even when only minute quantities of tissue are available. With the introduction of methodologies to purify and structurally-characterize molecules from small amounts of tissue and the application of high throughput immunological assays, one would predict that an assessment of parasitic helminths will yield a variety of novel drug candidates in the coming years.
TL;DR: The present period should be seen as a clear opportunity for public-private partnerships to develop simpler and more cost-effective tools and strategies for sustainable sleeping sickness control and surveillance, including diagnostics, treatment and vector control.
Abstract: SUMMARY Following a period characterized by severe epidemics of sleeping sickness, restoration of effective control and surveillance systems has raised the question of eliminating the disease from sub-Saharan Africa. Given sufficient political and financial support, elimination is now considered a reasonable aim in countries reporting zero or less than 100 cases per year. This success may lead health authorities across the affected region to downgrade the disease from ‘ neglected ’ to simply being ignored. In view of the significant levels of under-reporting of sleeping sickness mortality in rural communities, this could be a short-sighted policy. Loss of capacity to deal with new epidemics, which can arise as a consequence of loss of commitment or civil upheaval, would have serious consequences. The present period should be seen as a clear opportunity for public-private partnerships to develop simpler and more cost-effective tools and strategies for sustainable sleeping sickness control and surveillance, including diagnostics, treatment and vector control.
TL;DR: Results show that compounds interfering with P-gp transport activity could enhance IVM efficacy in sensitive isolates, and also restore IVM sensitivity in resistant nematodes, supporting the view that ABC transporters can play an important role in resistance to IVM, at least in the free-living stages of these economically important gastro-intestinal nematode parasites.
Abstract: P-glycoprotein (P-gp) homologues, belonging to the ATP Binding Cassette (ABC) transporter family, are thought to play an important role in the resistance of gastro-intestinal nematode parasites against macrocyclic lactones. The aim of this study was to investigate the influence of various P-gp interfering compounds on the efficacy of ivermectin (IVM) in sensitive and resistant nematode isolates. The feeding of IVM resistant and sensitive Teladorsagia circumcincta and Haemonchus contortus first-stage larvae (L1) was assessed using a range of IVM concentrations (0.08-40 nm) with or without P-gp inhibitors: valspodar, verapamil, quercetin, ketoconazole and pluronic P85. The P-gp inhibitors were selected on the basis of their ability to interfere with P-gp transport activity in an epithelial cell line over-expressing murine P-gp. In the presence of P-gp interfering agents, the in vitro susceptibility to IVM of both sensitive and resistant isolates of T. circumcincta and H. contortus was increased. These results show that compounds interfering with P-gp transport activity could enhance IVM efficacy in sensitive isolates, and also restore IVM sensitivity in resistant nematodes. These results support the view that ABC transporters can play an important role in resistance to IVM, at least in the free-living stages of these economically important gastro-intestinal nematodes.
TL;DR: Interestingly, the effect of habitat fragmentation on the prevalence of trypanosomes as multi-host parasites could not be observed in Litomosoides which probably has a higher host specificity and might be affected less by overall diversity loss.
Abstract: Anthropogenic influence on ecosystems, such as habitat fragmentation, impacts species diversity and interactions. There is growing evidence that degradation of habitats favours disease and hence affects ecosystem health. The prevalence of haemoparasites in the Common Fruit Bat (Artibeus jamaicensis) in a tropical lowland forest in Panama was studied. We assessed the relation of haemoparasite to the general condition of the animals and tested for possible association of haemoparasite prevalence to habitat fragmentation, with special focus on trypanosomes. Overall, a total of 250 A. jamaicensis sampled from fragmented sites, here man-made, forested islands in Lake Gatun, and sites in the adjacent, continuous forest in and around the Barro Colorado Nature Monument were examined. Using microscopy and DNA-sequencing 2 dominant types of haemoparasite infections, trypanosomes and Litomosoides (Nematoda) were identified. Trypanosome prevalence was significantly higher in bats from forest fragments, than in bats captured in continuous forest. We attribute this to the loss of species richness in forest fragments and specific characteristics of the fragments favouring trypanosome transmission, in particular changes in vegetation cover. Interestingly, the effect of habitat fragmentation on the prevalence of trypanosomes as multi-host parasites could not be observed in Litomosoides which probably has a higher host specificity and might be affected less by overall diversity loss.
TL;DR: In conclusion, parasite DNA amplification using general primers to determine the species composition of haemosporidian infections in individual hosts is not recommended and specific primers for each species and study area should be designed until a new method can efficiently discriminate both parasites.
Abstract: Avian Plasmodium and Haemoproteus parasites are easily detected by DNA analyses of infected samples but only correctly assigned to each genus by sequencing and use of a phylogenetic approach. Here, we present a restriction site to differentiate between both parasite genera avoiding the use of those analyses. Alignments of 820 sequences currently listed in GenBank encoding a particular cytochrome B region of avian Plasmodium and Haemoproteus show a shared restriction site for both genera using the endonuclease Hpy CH4III. An additional restriction site is present in Plasmodium sequences that would initially allow differentiation of both genera by differential migration of digested products on gels. Overall 9 out of 326 sequences containing both potential restriction sites do not fit to the general rule. We used this differentiation of parasite genera based on Hpy CH4III restriction sites to evaluate the efficacy of 2 sets of general primers in detecting mixed infections. To do so, we used samples from hosts infected by parasites of both genera. The use of general primers was only able to detect 25% or less of the mixed infections. Therefore, parasite DNA amplification using general primers to determine the species composition of haemosporidian infections in individual hosts is not recommended. Specific primers for each species and study area should be designed until a new method can efficiently discriminate both parasites.
TL;DR: This review focuses on some of the more ground-shifting advances of recent decades, particularly those at the molecular and cellular level that illuminate mechanisms underpinning the natural ecology of tick-host-pathogen interactions and the consequent epidemiology of zoonotic infections in humans.
Abstract: This review focuses on some of the more ground-shifting advances of recent decades, particularly those at the molecular and cellular level that illuminate mechanisms underpinning the natural ecology of tick-host-pathogen interactions and the consequent epidemiology of zoonotic infections in humans. Knowledge of components of tick saliva, now recognized as the central pillar in the tick's ability to complete its blood meal and the pathogen's differential ability to use particular hosts for transmission, has burgeoned with new molecular techniques. Functional studies have linked a few of them to saliva-assisted transmission of non-systemic infections between co-feeding ticks, the quantitative key to persistent cycles of the most significant tick-borne pathogen in Europe. Human activities, however, may be equally important in determining dynamic patterns of infection incidence in humans.
TL;DR: Progress made in schistosomiasis control across sub-Saharan Africa since the turn of the new millennium is reviewed, shedding light on the latest findings stemming from clinical, epidemiological, molecular and social sciences research, inclusive of public health interventions with monitoring and evaluation activities.
Abstract: Several other journal supplements have documented progress made in the control of schistosomiasis in Egypt, China and Brazil, however, with more than 97% of the schistosome infections now estimated to occur in Africa, the relevance of this special issue in Parasitology cannot be overemphasized. In total, 18 articles are presented, inclusive of a lead-editorial from the WHO highlighting a seminal resolution at the 54th World Health Assembly in 2001 that advocated de-worming. Facilitated by a US$ 30 million grant from the Bill and Melinda Gates Foundation in 2002, the Schistosomiasis Control Initiative subsequently fostered implementation of large-scale schistosomiasis (and soil-transmitted helminthiasis) control programmes in six selected African countries. From 2005, CONTRAST, a European union-funded consortium, was formed to conduct multi-disciplinary research pertaining to optimisation of schistosomiasis control. Progress made in schistosomiasis control across sub-Saharan Africa since the turn of the new millennium is reviewed, shedding light on the latest findings stemming from clinical, epidemiological, molecular and social sciences research, inclusive of public health interventions with monitoring and evaluation activities. New opportunities for integrating the control of schistosomiasis and other so-called neglected tropical diseases are highlighted, but more importantly, several opportune questions that arise from it frame the remaining challenges ahead for an enduring solution.
TL;DR: It is concluded that a scale-up and an upgrade in the fight against schistosomiasis are feasible and mandatory for the international community.
Abstract: The authors welcome the publication of a special issue in Parasitology pertaining to the control of schistosomiasis in Africa. In this editorial, we summarize the key features of the visionaryWorldHealth Assembly Resolution 54.19, passed some 8 years ago. Indeed, this resolution endorsed large-scale distribution of anthelminthic drugs for morbidity control of schistosomiasis and soil-transmitted helminthiasis, which should become the wider, global strategy of preventive chemotherapy in 2006. Looking into the future, the authors propose to further foster effective partnerships bringing to fruition field-level implementation and health policies adaptable to different epidemiological and socio-economic settings of the developing world, and conclude that a scale-up and an upgrade in the fight against schistosomiasis are feasible and mandatory for the international community.
TL;DR: It is indicated that there is potential for Australian native shrubs to play an anthelmintic role in grazing systems, and some plant biology factors which will need to be considered in order to maximize any anthel Mintic effects.
Abstract: SUMMARY Wemeasuredinvitroanthelminticactivityinextractsfrom85speciesofAustraliannativeshrub,withaviewtoidentifyingspecies able to provide a degree of worm control in grazing systems Approximately 40% of the species showed significantactivity in inhibiting development of Haemonchus contortus larvae The most active extracts showed IC 50 values of60–300 mg/mlPre-incubationwithpolyvinylpolypyrrolidine removedtheactivityfromsomeextracts,implicatingtanninsas the bioactive agent, while in other cases the pre-incubation had no effect, indicating the presence of other anthelminticcompounds Plant reproductive maturity (onset of flowering or fruiting) was associated with increasing anthelminticactivity in some species Variability was observed between plants of the same species growing in different environments,while variation between individual plants of the same species within a single field suggests the existence of distinctchemotypes Significant activity against adult H contortus worms in vitro was also demonstrated in a limited number ofextracts tested against this life stage Our study indicates that there is potential for Australian native shrubs to play ananthelmintic role in grazing systems, and highlights some plant biology factors which will need to be considered in orderto maximize any anthelmintic effectsKey words: plant extracts, perennial shrub, tannin, anthelmintic, Haemonchus contortus
TL;DR: Evidence point to autophagy as the predominant phenotype induced by the naphthoimidazoles, however, there are other pathways occurring concomitantly with variable intensities, justifying the need to detail the molecular features involved.
Abstract: SUMMARY In a screening of 65 derivatives of natural quinones using bloodstream trypomastigotes of Trypanosoma cruzi, the 3 naphthoimidazoles derived from beta-lapachone - N1, N2 and N3--were selected as the most active. Investigation of their mode of action led to the characterization of mitochondrion, reservosomes and DNA as their main targets, and stimulated further studies on death pathways. Ultrastructural analysis revealed both autophagic (autophagosomes) and apoptotic-like (membrane blebbing) phenotypes. Flow cytometry analysis showed, in N2-treated trypomastigotes, a small increase of phosphatidylserine exposure, and a large increase in the percentage of necrosis, caused by N1 or N2. These death phenotypes were not detected in treated epimastigotes. The strong increase in labelling of monodansyl cadaverine, the inhibition of the death process by wortmannin or 3-methyladenine, the overexpression of ATG genes in treated epimastigotes, together with ultrastructural evidence point to autophagy as the predominant phenotype induced by the naphthoimidazoles. However, there are other pathways occurring concomitantly with variable intensities, justifying the need to detail the molecular features involved.
TL;DR: R. pseudosphaerocephala can substantially reduce the viability of metamorph cane toads, and experimentally infected metamorph toads with the helminth.
Abstract: Cane toads (Bufo marinus) were introduced to Australia in 1935 and have since spread widely over the continent, generating concern regarding ecological impacts on native predators. Most Australian cane toad populations are infected with lung nematodes Rhabdias pseudosphaerocephala, a parasite endemic to New World (native-range) cane toad populations; presumably introduced to Australia with its toad host. Considering the high intensities and prevalence reached by this parasite in Australian toad populations, and public ardour for developing a control plan for the invasive host species, the lack of experimental studies on this host-parasite system is surprising. To investigate the extent to which this lungworm influences cane toad viability, we experimentally infected metamorph toads (the smallest and presumably most vulnerable terrestrial phase of the anuran life cycle) with the helminth. Infected toads exhibited reduced survival and growth rates, impaired locomotor performance (both speed and endurance), and reduced prey intake. In summary, R. pseudosphaerocephala can substantially reduce the viability of metamorph cane toads.
TL;DR: Morphological analysis of bloodstream forms and phylogenetic analysis at the 18S rDNA and gGAPDH loci demonstrated this trypanosome species to be genetically distinct and most similar to Trypanosoma bennetti.
Abstract: The morphology and genetic characterization of a new species of trypanosome infecting koalas (Phascolarctos cinereus) are described. Morphological analysis of bloodstream forms and phylogenetic analysis at the 18S rDNA and gGAPDH loci demonstrated this trypanosome species to be genetically distinct and most similar to Trypanosoma bennetti, an avian trypanosome with a genetic distance of 0.9% at the 18S rDNA and 10.7% at the gGAPDH locus. The trypanosome was detected by 18S rDNA PCR in the blood samples of 26 out of 68 (38.2%) koalas studied. The aetiological role of trypanosomes in koala disease is currently poorly defined, although infection with these parasites has been associated with severe clinical signs in a number of koalas. Based on biological and genetic characterization data, this trypanosome species infecting koalas is proposed to be a new species Trypanosome irwini n. sp.
TL;DR: It is concluded that geostatistical ZI models produce more accurate maps of helminth infection intensity than the spatial negative binomial ones.
Abstract: Progress has been made in mapping and predicting the risk of schistosomiasis using Bayesian geostatistical inference. Applications primarily focused on risk profiling of prevalence rather than infection intensity, although the latter is particularly important for morbidity control. In this review, the underlying assumptions used in a study mapping Schistosoma mansoni infection intensity in East Africa are examined. We argue that the assumption of stationarity needs to be relaxed, and that the negative binomial assumption might result in misleading inference because of a high number of excess zeros (individuals without an infection). We developed a Bayesian geostatistical zero-inflated (ZI) regression model that assumes a non-stationary spatial process. Our model is validated with a high-quality georeferenced database from western Cote d'Ivoire, consisting of demographic, environmental, parasitological and socio-economic data. Nearly 40% of the 3818 participating schoolchildren were infected with S. mansoni, and the mean egg count among infected children was 162 eggs per gram of stool (EPG), ranging between 24 and 6768 EPG. Compared to a negative binomial and ZI Poisson and negative binomial models, the Bayesian non-stationary ZI negative binomial model showed a better fit to the data. We conclude that geostatistical ZI models produce more accurate maps of helminth infection intensity than the spatial negative binomial ones.