The antibody response in mice to carrier-free synthetic polymers of Plasmodium falciparum circumsporozoite repetitive epitope is I-Ab-restricted: possible implications for malaria vaccines.

The immunogenicity of a novel synthetic peptide consisting of an average of 40 (Asn-Ala-Asn-Pro) repeats of the circumsporozoite protein of Plasmodium falciparum, (NANP)40, was studied in mice without using any carrier proteins. First, high titers of anti-(NANP)40 antibodies could be obtained after immunization of C57BL/6 mice. These antibodies also reacted with an extract of mosquitoes infected with P. falciparum sporozoites. C57BL/6 nu/nu mice did not produce antibodies against (NANP)40. Secondly, when 14 strains of mice with nine different H-2 haplotypes were immunized with (NANP)40 without carrier, only H-2b mice were found to produce anti-(NANP)40 antibodies, whereas all non-H-2b mice were consistently unresponsive. This response was demonstrated to be I-A-linked by using recombinant and mutant mice. I-Ab [B10.A(5R)] mice produced anti-(NANP)40 antibodies as well as H-2b inbred mice. B6CH-2bm12 I-Ab-mutant mice showed only a very low response. Third, the antibody response against (NANP)40 could be induced in nonresponder mice by immunization with the peptide coupled to a carrier protein. In view of the existence of such an exceptional H-2b restriction in the response to sporozoite synthetic peptides in mice, the triggering of peptide-specific T cell responses in humans receiving sporozoite malaria vaccines might be difficult to achieve.

Use of molecular probes and PCR for detection and typing of Leishmania - a mini-review

The use of molecular tools to detect and type Leishmania species in humans, reservoirs or sandflies has been pursued using different approaches. The polymerase chain reaction provided sensitivity to case this task, since the use of hybridization procedures alone employing specifics probes is hampered due to the low detection limit. In this report, we describe the different molecular targets used in our laboratory, aiming at the detection and specific typing of these protozoa. Different kits based on hybridization assays and PCR amplification using kinetoplast and nuclear targets are described and the results obtained from their use are reported.

The consequences of malaria infection in pregnant women and their infants

Preliminary results are presented from this study which indicate that 84.8 of pregnant women present at first antenatal visit with anemia (Hb 11g/dl) an 8.7 of their infants (n = 230) have a hemoglobin at birth below 14g/dl. There is an association between pregnancy anemia and malaria. A case control study in pregnant women and an infant cohort study to 18 months of age, are employed to study the cause and effects of anemia and malaria on women and their infants health.

Immune mechanisms underlying the premunition against Plasmodium falciparum malaria

The most unique characteristic of a parasite when it is in its normal host is the ability to make itself tolerated, which clearly indicates that it has sophisticated means to ensure the neutrality of its host. This is true also in the case of Plasmodium falciparum, since after numerous malaria attacks an equilibrium is reached with a chronic stage of infection, characterized by a relatively low parasitemia, and low or no disease (Sergent & Parrot 1935). We shall briefly review the main characteristics of this state of "premunition", and present data suggesting that the underlying mechanisms of defense rely on the cooperation between cell and antibodies, leading to an antibody dependent cellular inhibition of the intra-erythrocytic growth of the parasite.

Transport pathways in the malaria-infected erythrocyte: characterization and their use as potential targets for chemotherapy

The intraerythrocytic malarial parasite is involved in an extremely intensive anabolic activity while it resides in its metabolically quiescent host cell. The necessary fast uptake of nutrients and the discharge of waste product, are guaranteed by parasite-induced alterations of the constitutive transporters of the host cell and the production of new parallel pathways. The membrane of the host cell thus becomes permeable to phospholipids, purine bases and nucleosides, small non-electrolytes, anions and cations. When the new pathways are quantitatively unimportant, classical inhibitors of native transporters can be used to inhibit parasite growth. Several compounds were found to effectively inhibit the new pathways and consequently, parasite growth. The pathways have also been used to introduce cytotoxic agents. The parasitophorous membrane consists of channels which are highly permeable to small solutes and display no ion selectivity. Transport of some cations and anions across the parasite membrane is rapid and insensitive to classical inhibitors, and in some cases it is mediated by specific antiporters which respond to their respective inhibitors. Macromolecules have been shown to reach the parasitophorous space through a duct contiguous with the host cell membrane, and subsequently to be endocytosed at the parasite membrane. The simultaneous presence of the parasitophorous membrane channels and the duct, however, is incompatible with experimental evidences. No specific inhibitors were found as yet that would efficiently inhibit transport through the channels or the duct.

Chimpanzees and supporting models in the study of malaria pre-erythrocytic stages

Chimpanzees are being used in the study of immune response to Plasmodium falciparum malaria pre-erythrocytic stages (MPES). Responses induced by immunisation with recombinant/synthetic antigens and by irradiated sporozoites are being evaluated in a model system that is phylogenetically close to humans and that is amenable to limited manipulation not possible in humans. The value of chimpanzees for the in-depth study of immunological mechanisms at work in MPES-induced protection are discussed. A total number of 7 chimpanzees have been used to evaluate the immune response to recombinant antigens, and 5 have been challenged with large numbers of sporozoites, followed by surgical liver-wedge resection, in order to generate infected liver tissue for histological and immunological studies. As a complementary model, SCID mice carrying live, transplanted human and primate hepatocytes have been inoculated with sporozoites and infection of transplanted cells has been monitored by histological and immunological methods. In ongoing experiments chimpanzees are being immunised with MPES-derived lipopeptides that have been shown to overcome MHC restriction in mice, and with irradiated sporozoites.

Quantitative ultrasound for the detection and management of osteoporosis.

Quantitative ultrasound (QUS) appears to be developing into an acceptable, low-cost and readily-accessible alternative to dual X-ray absorptiometry (DXA) measurements of bone mineral density (BMD) in the detection and management of osteoporosis. Perhaps the major difficulty with their widespread use is that many different QUS devices exist that differ substantially from each other, in terms of the parameters they measure and the strength of empirical evidence supporting their use. But another problem is that virtually no data exist outside of Caucasian or Asian populations. In general, heel QUS appears to be most tested and most effective. Some, but not all heel QUS devices are effective assessing fracture risk in some, but not all populations, the evidence being strongest for Caucasian females > 55 years old, though some evidence exists for Asian females > 55 and for Caucasian and Asian males > 70. Certain devices may allow to estimate the likelihood of osteoporosis, but very limited evidence exists supporting QUS use during the initiation or monitoring of osteoporosis treatment. Likely, QUS is most effective when combined with an assessment of clinical risk factors (CRF); with DXA reserved for individuals who are not identified as either high or low risk using QUS and CRF. However, monitoring and maintenance of test and instrument accuracy, precision and reproducibility are essential if QUS devices are to be used in clinical practice; and further scientific research in non-Caucasian, non-Asian populations clearly is compulsory to validate this tool for more widespread use.

Simian malaria at two sites in the Brazilian Amazon: I-The infection rates of Plasmodium brasilianum in non-human primates

The parasite that causes simian malaria in the Brazilian Amazon, Plasmodium brasilianum, is infective to man. In this region, where humans live within and in close proximity to the forest, it was suspected that this parasite could be the cause of a zoonosis. A study was performed in the areas surrounding two hydroelectric plants in the Amazon, Balbina and Samuel, aiming at determining the zoonotic potential of this parasite. P. brasilianum was detected in, respectively, 15.8% and 9.9% of 126 and 252 primates belonging to seven and eight species examined from Balbina and Samuel. The highest malaria infection rates were found among the red-howler monkey Alouatta seniculus straminea (32.3%), the bearded-saki Chiropotes satanas chiropotes (50%) and the spider-monkey Ateles paniscus paniscus (2[1+]) from Balbina and in the squirrel-monkey Saimiri ustus (21%) and the black-faced-spider-monkey Ateles paniscus chamek (28.6%) from Samuel.

Head motion detection using FID navigators.

This work explores a concept for motion detection in brain MR examinations using high channel-count RF coil arrays. It applies ultrashort (<100 μsec) free induction decay signals, making use of the knowledge that motion induces variations in these signals when compared to a reference free induction decay signal. As a proof-of-concept, the method was implemented in a standard structural MRI sequence. The stability of the free induction decay-signal was verified in phantom experiments. Human experiments demonstrated that the observed variations in the navigator data provide a sensitive measure for detection of relevant and common subject motion patterns. The proposed methodology provides a means to monitor subject motion throughout a MRI scan while causing little or no impact on the sequence timing and image contrast. It could hence complement available motion detection and correction methods, thus further reducing motion sensitivity in MR applications.