Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An invertebrate intestinal mucin gene, AgMuc1, was isolated from the malaria vector mosquito Anopheles gambiae. The predicted 122-residue protein consists of a central core of seven repeating TTTTVAP motifs flanked by hydrophobic N- and C-terminal domains. This structure is similar to that of mucins that coat the protozoan parasite Trypanosoma cruzi. Northern blot analysis indicated that the gene is expressed exclusively in the midgut of adult mosquitoes. A length polymorphism and in situ hybridization were used to genetically and cytogenetically map AgMuc1 to division 7A of the right arm of the second chromosome. The subcellular localization of the encoded protein in tissue culture cells was examined by using a baculovirus vector to express AgMuc1 protein tagged with the green fluorescent protein (GFP). The results indicated that this protein is found at the cell surface and that both hydrophobic domains are required for cell surface targeting. We propose that AgMuc1 is an abundant mucin-like protein that lines the surface of the midgut microvilli, potentially protecting the intestinal epithelium from the proteinase-rich environment of the gut lumen. An intriguing possibility is that, as an abundant surface protein, AgMuc1 may also interact with the malaria parasite during its invasion of the mosquito midgut.
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PMID:A cell surface mucin specifically expressed in the midgut of the malaria mosquito Anopheles gambiae. 1031 32

Invasion of the malarial parasite into a vector mosquito begins when the motile ookinete transverses the gut epithelium. Adhesive proteins that may mediate this invasive process have not been identified to date. We found that a molecule with an adhesive protein-like structure was expressed in the ookinete of Plasmodium berghei. This protein is structurally homologous to circumsporozoite protein and thrombospondin-related adhesive protein (TRAP)-related protein, CTRP, of Plasmodium falciparum. We named it P. berghei CTRP (PbCTRP) and report here its structure and manner of expression. PbCTRP has six integrin I region-like domains and seven thrombospondin-like domains in its putative extracellular region. This structure is similar to that of CTRP and TRAPs of malaria sporozoite. The putative transmembrane and cytoplasmic regions of PbCTRP, CTRP, and TRAP also have conserved amino acid sequences. PbCTRP is produced at least 10 h after fertilization when zygotes begin transformation to ookinetes. In the mature ookinete, PbCTRP is located mainly in the anterior cytoplasm. The staining pattern was also similar to TRAP in the sporozoite. We suggest that PbCTRP may play a role in ookinete invasive motility and belongs to a protein family together with TRAP and other structurally related proteins of apicomplexan parasites.
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PMID:Structure and expression of an adhesive protein-like molecule of mosquito invasive-stage malarial parasite. 1037 90

Experimental infections of laboratory-reared anopheline mosquitoes were carried out with 57 Plasmodium falciparum gametocyte carriers from Cameroon. Prevalence of infected mosquitoes and oocyst intensity were determined by two independent methods. Young P. falciparum oocysts were detected on day 2 after feeding using an immunofluorescent assay, and the results were compared with direct microscopic examination of midgut oocysts on day 7 postinfection. The immunofluorescent assay was based on a FITC-labeled anti-25-kDa monoclonal antibody, while the direct microscopy was performed on midguts stained with 2% mercurochrome. Young oocysts were easily detected by their typical and bright green-fluorescing Pfs25 positive coat and their characteristic pattern of pigment granules under transmitted white light examination. The agreement between the results of the two methods was assessed using the Kappa coefficient on prevalences of positive infections and the interclass correlation coefficient on arithmetic mean oocyst load per infected midgut. The results indicated a low agreement between the two methods for the comparison of prevalences of infected mosquitoes. However, this agreement was near perfect for the comparison of mean oocyst intensities. Prevalences of positive infections and the overall number of parasites per positive gut were significantly correlated for both methods. Thus, the immunofluorescent test could be an appropriate tool for early determination of malaria infection in mosquitoes, particularly under laboratory conditions. The possible applications of this immuno-fluorescent technique are discussed.
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PMID:The use of anti-Pfs 25 monoclonal antibody for early determination of Plasmodium falciparum oocyst infections in Anopheles gambiae: comparison with the current technique of direct microscopic diagnosis. 1040 62

Multiple dose pharmacokinetics of artemether and dihydroartemisinin were investigated in chinese patients treated for malaria. They received over 2 days either 4 x 80 mg artemether orally (n = 48) or 4 x 80-480 mg co-artemether (n = 40), a combination of artemether and lumefantrine (benflumetol). Lag time = 0.48 h (mean), Cmax after first dose = 157 ng/ml, t(max) = 1.73 h and elimination half-life = 1.16 h. The lag and absorption times were 0.5 h longer for co-artemether compared with artemether. Dihydroartemisinin paralleled artemether pharmacokinetics. Artemether Cmax after the last dose was one-third of the Cmax after the first dose while, inversely, dihydroartemisinin Cmax increased over time. We suggest that auto-induction of gut mucosa enzymes and/or liver enzymes causes a time-dependent increase in first-pass metabolisation of artemether.
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PMID:Multiple dose pharmacokinetics of artemether in Chinese patients with uncomplicated falciparum malaria. 1041 61

This work investigated the feasibility of dermal and transdermal delivery of doxycycline from vehicles containing Migliol 840 (M840) and ethanol. Delivery of the drug via the skin would provide a useful alternative to oral delivery, which has many undesirable side-effects, such as oesophageal ulceration and disturbance of the normal gut flora. Potential applications include malaria prophylaxis, and the treatment of acne vulgaris, Lyme disease and Reiter syndrome. Experiments were performed to determine the permeation of doxycycline across excised full-thickness human skin and heat-separated epidermal membranes from saturated solutions in ethanol, 1:1 and 2:1 ethanol/M840. Unusual burst behaviour was observed using an ethanol vehicle, possibly as a result of the formation of dimers at saturation. Doxycycline permeated to a higher degree from ethanolic vehicles when M840 is present, suggesting that M840 is capable of enhancing the permeation of doxycycline. The flux across full-thickness skin was highest from a 2:1 ethanol:M840 vehicle (2.41 microg cm(-2) h(-1)), sufficient to deliver 282 microg l(-1) using an area of application of 30 cm(2). The data also produced unexpected results in that permeability across heat separated skin was an order of magnitude greater than across full-thickness skin (28.75 microg cm(-2) h(-1) for the 2:1 ethanol:M840 vehicle). Depth profiling indicated that the drug distributed quite evenly throughout the epidermis. The mean amount of doxycycline recovered from the epidermis at the end of a permeation experiment was 458.4 microg ml(-1). This was far higher than the volume of extractable lipid present in the same unit area, approximately 52.3 microg ml(-1) and indicated that a large proportion of the drug must have been located within the proteinaceous domain. The data therefore suggest (1) significant amounts of doxycycline can be administered into and across the skin; (2) M840 is a potentially useful enhancing vehicle; and (3) the transcellular route was of significance.
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PMID:In vitro dermal and transdermal delivery of doxycycline from ethanol/migliol 840 vehicles. 1054 55

Polymerase chain reaction (PCR)-based genotyping of oocysts dissected from mosquito midguts has previously been used to investigate overall levels of inbreeding within malaria parasite populations. We present a re-analysis of the population structure of Plasmodium falciparum malaria using diploid genotypes at three antigen-encoding loci in 118 oocysts dissected from 34 mosquitoes. We use these data to ask whether mating is occurring at random within the mosquito midgut, as is generally assumed. We observe a highly significant deficit of heterozygous oocysts within mosquitoes at all three loci, suggesting that fusion of gametes occurs non-randomly in the mosquito gut. A variety of biological explanations, such as interrupted feeding of mosquitoes, positive assortative mating and outcrossing depression, could account for this observation. However, an alternative artefactual explanation--the presence of non-amplifying or null alleles--can account for the observed data equally well, without the need to invoke non-random mating. To evaluate this explanation further, we estimate the frequencies of null alleles within the oocyst population using maximum likelihood, by making the assumption that non-amplifying oocysts at any of the three loci are homozygous for null alleles. Observed levels of visible heterozygotes fit closely with those expected under random mating when non-amplifying oocysts are accounted for. Other lines of evidence also support the artefactual explanation. Overall inbreeding coefficients have been recalculated in the light of this analysis, and may be considerably lower than those estimated previously. In conclusion, we suggest that the deficit of heterozygotes observed is unlikely to indicate non-random mating within the mosquito gut and is better explained by misscoring of heterozygotes as homozygotes.
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PMID:Do malaria parasites mate non-randomly in the mosquito midgut? 1089 65

Malaria vector surveys were carried out in 8 provinces in Lao PDR in 1999. The surveys were conducted in 4 provinces - Savannakhet, Champasak, Luang Perbang and Sayaboury in May and in another 4 provinces - Bolikhamsay, Sarvan, Sekong and Vientiane in December 1999. Bare leg collection were carried out indoors and outdoors from 6 pm to 5 am. All anopheline mosquitos were identified, dissected and the gut, gland and ovaries were examined. A total of 438 Anopheles mosquitos belonging to 19 species were obtained. Of these only 3 species were found to be infected with oocysts - An. maculatus, An. dirus and An. minimus. All these species were found biting both indoors and outdoors. An. aconitus was the predominant species obtained in the December collection but its vectorial status remains unknown.
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PMID:Preliminary studies of Anopheles mosquitos in eight provinces in Lao PDR. 1148 1

We developed a method for the in vitro production of mature Plasmodium vivax ookinetes. Gametocytemic blood was collected from 98 P. vivax-infected patients reporting to malaria clinics in Maesod and Maekasa Districts, Tak Province, Thailand. Briefly, gametogenesis was induced using xanthurenic acid and parasites were separated by density gradient centrifugation and then cultured in RPMI-1640, pH 7.8-8.2. At the same time that blood was collected, 200 Anopheles dirus mosquitoes were allowed to feed on each patient. Mosquito midguts were removed 2-36 hr postfeeding, and gut contents were smeared onto glass slides, as were cultured samples from varying time points. Slides were stained with Giemsa, and the in vitro and mosquito development of ookinetes compared. Mature ookinetes were produced in 48.0% (47/98) of in vitro cultures, with a total yield ranging from 10 to 248,500 (mean = 15,523, median = 600) ookinetes produced per 5 ml blood. The temporal development and the morphology of the P. vivax ookinetes produced in vitro was similar to that observed in the A. dirus mosquitoes. The method that we describe is simple, can be used at remote sites without sophisticated equipment, and yields high numbers of clean ookinetes. This method of producing mature P. vivax ookinetes will be a useful tool for studies on ookinetes in P. vivax endemic regions.
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PMID:Development of a method for the in vitro production of Plasmodium vivax ookinetes. 1153 65

Malaria is still a leading cause of morbidity and mortality in human populations. Problems, including drug-resistant parasites and insecticide resistant mosquitoes, ensure the continued hold of malaria in the tropics and sub-tropics. Each year around 100 million cases of malaria result in at least 50,000 deaths outside of sub-Saharan Africa; within sub-Saharan Africa itself, malaria causes around one million child deaths per year. New approaches for malaria control are badly needed and much effort has gone to develop malaria vaccines. In addition to giving personal protection, most such vaccines would also tend to reduce the transmission of malaria. One class of vaccine is being developed specifically for this purpose--the malaria transmission-blocking vaccines (TBV). TBVs are based upon antigens expressed on the surface of the sexual and mosquito mid-gut stages of malaria parasites. These antigens are the targets of antibodies induced by vaccination of the host and ingested with the parasites in a mosquito blood meal. The antibodies act by inhibiting the parasite's development within the mosquito itself and they thereby prevent the onward transmission of the parasites. TBVs could contribute to the total interruption of malaria transmission in many locations with relatively low transmission rates, mostly outside sub-Saharan Africa. Under almost all transmission rates, however, TBVs would help reduce malaria incidence and malaria-related morbidity and mortality. Promising recombinant TBV candidate antigens for the two main human malaria parasite species, Plasmodium falciparum and Plasmodium vivax, have been produced and tested in the laboratory; one has undergone early clinical trials.
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PMID:Current developments in malaria transmission-blocking vaccines. 1172 98

As a result of dramatic increase in malaria cases in Sa Kaeo Province from 666 cases in 1995 to 4,381 in 1997, a brief entomological study was carried out during January 1998 to December, 1999 in Pa Rai subdistrict where most malaria cases were reported. Of fourteen species of mosquitos found, only Anopheles barbirostris group was the most abundant species throughout the year. Adult identification was not able to confirm species within An. barbirostris group, particularly between An. barbirostris and An. campestris because of morphological resemblance. Therefore, the barbirostris group captured in this study is reported to be either An. barbirostris or An. campestris. The seasonal prevalence of barbirostris/campestris was bimodal in distribution (September and November) and coincided well with malaria occurrence in this area. Human landing collections revealed high adult densities with 20 bites/person-night for mean indoor density and 53.5 bites/person-night for mean outdoor density. The biting peak was during 21.00-24.00 hours. Among 223 barbirostris/campestris dissected for oocysts and sporozoites only one gut from the outdoor collection in November was infected with oocysts. There were no sporozoites detected in salivary glands of all mosquitos collected. This appears to indicate that in the absence of major vectors local species may serve as potential transmitters of malaria in Thailand.
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PMID:Anopheles barbirostris/campestris as a probable vector of malaria in Aranyaprathet, Sa Kaeo Province. 1204 47


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