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PubMed2001

Domains of invasion organelle proteins from apicomplexan parasites are homologous with the Apple domains of blood coagulation factor XI and plasma pre-kallikrein and are members of the PAN module superfamily.

Micronemes are specialised organelles, found in all apicomplexan parasites, which secrete molecules that are essential for parasite attachment to and invasion of host cells. Regions of several microneme proteins have sequence similarity to the Apple domains (A-domains) of blood coagulation factor XI (FXI) and plasma pre-kallikrein (PK). We have used mass spectrometry on a recombinant-expressed, putative A-domain from the microneme protein EtMIC5 from Eimeria tenella, to demonstrate that three intramolecular disulphide bridges are formed. These bridges are analogous to those that stabilise A-domains in FXI and PK. The data confirm that the apicomplexan domains are structural homologues of A-domains and are therefore novel members of the PAN module superfamily, which also includes the N-terminal domains of members of the plasminogen/hepatocyte growth factor family. The role of A-domains/PAN modules in apicomplexan parasites is not known, but their presence in the microneme suggests that they may be important for mediating protein-protein or protein-carbohydrate interactions during parasite attachment and host cell invasion.

Amino Acid Motifs↗
PubMed2001

Nutrient acquisition by intracellular apicomplexan parasites: staying in for dinner.

The intracellular forms of the apicomplexan parasites Plasmodium, Toxoplasma and Eimeria reside within a parasitophorous vacuole. The nutrients required by these intracellular parasites to support their high rate of growth and replication originate from the host cell which, in turn, takes up such compounds from the extracellular milieu. Solutes moving from the external medium to the interior of the parasite, are confronted by a series of three membranes --the host cell membrane, the parasitophorous vacuole membrane and the parasite plasma membrane. Each constitutes a potential permeability barrier which must be either crossed or bypassed. It is the mechanisms by which this occurs that are the subject of this review.

Animals↗
PubMed2002

Biogenesis of iron-sulphur clusters in amitochondriate and apicomplexan protists.

During the last 4 years there has been an enormous interest in the question how iron-sulphur ([Fe-S]) clusters, which are essential building blocks for life, are synthesised and assembled into apo-proteins, both in prokaryotes and in eukaryotes. The emerging picture is that the basic mechanism of this pathway has been well conserved during evolution. In yeast and probably all other eukaryotes the mitochondrion is the place where [Fe-S] clusters are synthesised, even for extramitochondrial [Fe-S] cluster-containing proteins, and a number of proteins have been functionally characterised to a certain extent within this pathway. However, almost nothing is known about this aspect in parasitic protists, although recent studies of amitochondriate protists and on the plastid-like organelle of apicomplexan parasites, the apicoplast, have started to change this. In this article I will summarise the current view of [Fe-S] cluster biogenesis in eukaryotes and discuss its implications for amitochondriate protists and for the plastid-like organelle of apicomplexan parasites.

Animals↗
PubMed1997

The importance of transmission-blocking immunity in the control of infections by apicomplexan parasites.

Transmission-blocking immunity may have great potential for use in the control of diseases caused by apicomplexan parasites. In this review I will describe our work on the application of transmission-blocking immunity to the control of the Eimeria parasite and compare our results to those working on transmission-blocking immunity against Cryptosporidium and Plasmodium. Eimeria causes the disease known as coccidiosis in domestic animals. Coccidiosis is particularly problematic in the chicken industry, mainly due to the crowded rearing conditions under which chicks are raised. In our work we identified, isolated and characterized 3 major gametocyte antigens (230 kDa, 82 kDa and 56/54 kDa) of Eimeria maxima. We used these native glycoproteins to immunize laying hens that, via the egg yolk, provide large amounts of transmission-blocking maternal antibodies to offspring chicks. We demonstrated that hatchlings from immunized hens shed 60-80% fewer oocysts (i.e. the infective stage of the life-cycle of Eimeria) than those from control hens. Such a reduction in oocyst output acts to significantly reduce parasite numbers in the litter of chicks raised in floor pens. This reduction in oocyst output is comparable to that seen using the most effective coccidiostat drugs and is probably sufficient to control coccidiosis under field conditions. Based on our results together with those of other groups working on transmission-blocking immunity against Cryptosporidium and Plasmodium, it appears that this immunological approach holds great promise for the control of apicomplexan parasites that cause diseases in both animals and man.

Animals↗
PubMed1998

Control of coccidiosis: lessons from other sporozoa.

Coccidiosis is the most important parasitic infection in poultry worldwide and also causes problems in cattle, sheep and goats. Control is largely limited to good husbandry and prophylactic chemotherapy using a range of drugs against which resistance is rapidly acquired. Attempts at vaccination using conventional vaccines have been disappointing and there is now a need for a new approach. Research into the immunology of coccidiosis has lagged behind that of other sporozoans and there are useful lessons that might be learned from studies on toxoplasmosis, cryptosporidiosis, theileriosis and malaria. In these infections the emphasis has turned to the cytokine network that drives the response towards protection. Central to these studies are the roles of interferon-gamma, interleukin-12 and activated macrophages with the involvement of nitric oxide in parasite killing. Cytotoxic T cells have also increasingly been implicated. Research has shown that different immune responses can be elicited by manipulating the cytokine system and these new concepts can be applied to the design of peptide or recombinant vaccines, and the possibilities of developing such vaccines against coccidiosis will be discussed.

Animals↗
PubMed2000

Impact of a plastid-bearing endocytobiont on apicomplexan genomes.

Both the chromosomal and extrachromosomal components of the apicomplexan genome have been supplemented by genes from a plastid-bearing endocytobiont: probably an algal cell. The sequence of the apicomplexan plastid's vestigial genome indicates that a large number (>100) of genes of endocytobiotic origin must have transferred laterally to the host cell nucleus where they control maintenance of the plastid organelle and supply its functional components by means of post-translational protein trafficking. Should the nuclear genes prove to be less divergent phylogenetically than those left on the plastid genome, they might give better clues than we have at present to the origin of the plastid-bearing endocytobiont. Most of these nuclear genes still await discovery, but the on-going genome sequencing project will reveal the function of the organelle, as well as many "housekeeping" processes of interest on a wider front. The plastid's own protein synthetic machinery, being cyanobacterial in origin, offers conventional targets for antibiotic intervention, and this is discussed here using a structural model of elongation factor Tu. Uncovering the vital function(s) of the plastid organelle will provide new drug targets.

Amino Acid Sequence↗
PubMedDate not supplied

Insecticide-treated materials, mosquito adaptation and mass effect: entomological observations after five years of vector control in Burkina Faso.

Insecticide-treated bednets and curtains have been shown to be successful in reducing malaria transmission and child mortality in Africa over periods of up to 2 years. A major concern relating to this approach is that, in time, it will be compromised by the selection of mosquito genotypes that are resistant at the biochemical or behavioural level. We report entomological data from a large area in Burkina Faso where insecticide-treated curtains have been in use for up to 5 years. Longitudinal indoor and outdoor CDC light-trap catches were performed in 4 sentinel villages. In addition cross-sectional surveys using indoor spray catches and outdoor CDC light-trap catches were performed each September in a larger number of villages, including 8 located outside the intervention area. We found no evidence of the selection of mosquito phenotypes that might compromise the intervention. Indoor and outdoor vector densities remained very low after 5 years of intervention, both compared with pre-intervention levels and with concurrent levels outside the intervention area. We found no evidence of a switch to outdoor rather than indoor biting. The proportion of blood meals taken on humans may have decreased but our data are inconclusive on this point. We observed higher vector densities and sporozoite rates at the periphery of the intervention zone than at the centre, which may reflect re-invasion of peripheral villages by mosquitoes from outside the intervention area. In 'real life' programmes, with perhaps patchy, less than optimal coverage, the protection against malaria transmission provided to individuals using insecticide-treated materials may be less than that achieved in the randomized controlled trials which demonstrated an impact of insecticide-treated materials on child mortality.

Animals↗
PubMedDate not supplied

Area effects of bednet use in a malaria-endemic area in Papua New Guinea.

Relationships between area coverage with insecticide-free bednets and prevalence of Plasmodium falciparum were investigated in 7 community-based surveys over a 33-month period in 1990-93 in 6 villages in the Wosera area of Papua New Guinea. Spatial patterns in circumsporozoite rates for P. falciparum, P. vivax isomorphs K210 and K247, and P. malariae, and the proportions of mosquito blood meals positive for specific human, goat, cat, dog and pig antigens were determined using ELISAs. P. falciparum prevalence in humans was better explained by bednet coverage in the immediate vicinity than by personal protection alone. Circumsporozoite rates for both P. falciparum and P. vivax were also inversely related to coverage with bednets. There was some increase in zoophagy in areas with high coverage, but relatively little effect on the human blood index or on overall mosquito densities. In this setting, protracted use of untreated bednets apparently reduces sporozoite rates, and the associated effects on prevalence are greater than can be accounted for by personal protection. Even at high bednet coverage most anophelines feed on human hosts, so the decreased sporozoite rates are likely to be largely due to reduction of mosquito survival. This finding highlights the importance of local vector ecology for outcomes of bednet programmes and suggests that area effects of untreated bednets should be reassessed in other settings.

Adolescent↗
PubMedDate not supplied

The role of four anopheline species (Diptera: Culicidae) in malaria transmission in coastal Tanzania.

Malaria is holoendemic in coastal Tanzania with Anopheles funestus and members of the A. gambiae complex being mainly responsible for transmission. Over a 4 months' sampling period 2222 anopheline mosquitoes were collected using light-traps and indoor resting catches, of which 58.6% were A. gambiae, 7.6% A. arabiensis, 6.9% A. merus and 26.9% A. funestus. Plasmodium falciparum circumsporozoite antigen (CSA) rates were: A. funestus 6.05% (n = 479), A. gambiae 8.4% (n = 1042), A. arabiensis 7.3% (n = 136) and A. merus 9.8% (n = 122). The P. malariae CSA rate for all anophelines was 0.07% (n = 1862). Estimated sporozoite densities were less than 2000 for at least 50% of all the positive mosquitoes. Along the coast the abundance of A. merus (41.3%) and A. gambiae (46.1%) was similar, and their CSA rates were comparable (11.6% and 12.5%, respectively) and higher than those for A. arabiensis (7.7%) and A. funestus (4.6%). These results indicate that A. merus plays an unexpectedly important role in malaria transmission in coastal Tanzania.

Animals↗
PubMedDate not supplied

Comparative susceptibility of two members of the Anopheles oswaldoi complex, An. oswaldoi and An. konderi, to infection by Plasmodium vivax.

We compared the susceptibility of Anopheles oswaldoi and An. konderi to infection by Plasmodium vivax based on the proportion of mosquitoes presenting oocysts and sporozoites. Anophelines were captured in the State of Acre and Rondônia, Brazilian Amazon, and used to obtain F1 progenies. After emergence of adults, male genitalia of mosquitoes of each family were dissected in order to identify them as either An. oswaldoi or An. konderi. F1 progenies of field-captured An. oswaldoi, An. konderi and An. darlingi (used as control) were fed simultaneously on P. vivax-infected blood. Mosquitoes were dissected on day 10-12 after feeding and examined for the presence of oocysts and sporozoites. Both An. oswaldoi and An. konderi developed oocysts in the midguts, however, the percentage of oocyst-positive mosquitoes for An. oswaldoi (13.8%) was higher than for An. konderi (3.3%), and only An. oswaldoi developed salivary infection with sporozoites (6.9% of positivity). Infection rates in An. darlingi ranged from 22.5% to 30.0% for both oocysts and sporozoites. These results indicate that An. oswaldoi can transmit P. vivax and suggest that it is more susceptible than An. konderi. Although An. oswaldoi is an exophilic and zoophilic species, it may be involved in malaria transmission as possibly occurred in the State of Acre.

Animals↗
PubMedDate not supplied

Wide-scale installation of insecticide-treated curtains confers high levels of protection against malaria transmission in a hyperendemic area of Burkina Faso.

In a region of Sudanese savannah in Burkina Faso, insecticide-treated curtains were installed in 8 out of 16 zones, each covering an area of about 50 km2. Longitudinal entomological monitoring using CDC light traps was performed in 4 villages (2 intervention, 2 control) over a period of 3 years (including 1 year prior to intervention). In the 3rd year a cross-sectional entomological survey using spray catches was performed in 84 villages (40 intervention). Indoor vector densities in protected houses showed large reductions (P = 0.01). The available data were also consistent with an impact on outdoor and unprotected indoor densities. The proportion of mosquitoes carrying sporozoites was 4.1% in protected villages compared with 11.5% in unprotected villages (P = 0.07). Entomological inoculation rates fell substantially (P = 0.01), reflecting these reductions. The impact of this intervention on mosquito survival appears to have been greater than those in similar trials conducted in the Gambia, Ghana and Kenya in which the intervention was applied over smaller areas.

Animals↗