A new species of the planthopper genus Conosimus associated with an endemic shrub in southern Spain.

The poorly-known genus Conosimus Mulsant et Rey, 1855 (Hemiptera: Fulgoroidea: Issidae) includes six species and is briefly reviewed. Adults and fifth instars of a new species, Conosimus baenai n sp., are described and compared with other species in the genus. The new species is associated with an endemic shrub, Echinospartum boissieri, in Jaen, Spain, in the south of the Iberian Peninsula, one of the richest botanical areas of the Mediterranean Basin.

Use of an immunochromatographic kit for the rapid detection of Mycobacterium tuberculosis from broth cultures.

In settings of high human immunodeficiency virus (HIV) prevalence, culture confirmation, preferably by liquid culture, is required for the diagnosis of tuberculosis (TB). However, long delays with phenotypic identification offsets the short turnaround time of liquid cultures. We report here the advantages of using a commercial immunochromatographic (ICT) assay targeting the Mycobacterium tuberculosis protein 64 (MPT-64) Ag and compare it with the Accuprobe MTB complex molecular probe assay. The performance of the ICT kit was excellent, with sensitivity, specificity, positive and negative predictive values of respectively 97%, 100%, 100%, and 92%. The kit requires a 15-min assay time, is easy to perform and is a good method for simplifying the diagnosis of TB.

Differential non-responsiveness in humans of candidate Plasmodium falciparum vaccine antigens.

Synthetic subunit vaccines to sporozoites, merozoites, and gametes are being developed for malaria. The vaccine strategy assumes that the population to be immunized will respond favorably to these vaccine antigens. Using sera of 35 adults and 50 children from the The Gambia, West Africa, where Plasmodium falciparum is highly endemic, we examined the humoral immune response to candidate malaria vaccine antigens from sporozoites, merozoites, and gametes. We observed widespread restricted immunogenicity to defined parasite antigens in children and adults. HLA typing of adult lymphocytes demonstrated a marked diversity in HLA haplotypes in this population. Our results and those from our studies in mice suggest that genetic factors may partly explain the immunological non-responsiveness. This may necessitate re-evaluation of the malaria vaccine strategy.

Relapse of tularemia after aminoglycoside therapy: case report and discussion of therapeutic options.

We describe a patient with ulceroglandular tularemia who initially responded to therapy with gentamicin but then clinically relapsed. Ciprofloxacin was subsequently given for 28 days, and the patient was clinically cured. Aminoglycosides have been considered the drugs of choice in the treatment of tularemia; however, potential alternative treatments do exist. We review the English-language literature on this topic.

Genetic differentiation among host-associated Alebra leafhoppers (Hemiptera: Cicadellidae).

The limited importance ascribed to sympatric speciation processes via host race formation is partially due to the few cases of host races that have been reported among host populations. This work sheds light on the taxonomy of Alebra leafhoppers and examines the possible existence of host races among host-associated populations. The species of this genus show varying degrees of host association with deciduous trees and shrubs and, frequently, host populations of uncertain taxonomic status coexist and occasionally become pests. Allozyme electrophoresis of 21 Greek populations including sympatric, local and geographically distant samples collected on 13 different plant species, show that they represent at least five species: A. albostriella Fallén, A. viridis (Rey) (sensu Gillham), A. wahlbergi Boheman and two new species. Of these, one is associated to Quercus frainetto and other is specific to Crataegus spp. Significant genetic differences among sympatric and local host populations were found only in A. albostriella, between populations on Turkey oak, beech and common alder. It is suggested that the last two of these host populations may represent different host races. The results show that both the host plant and geographical distance affect the patterns of differentiation in the genus. The formation of some species seems to have been the result of allopatric speciation events while, for others, their origin can be equally explained either by sympatric or allopatric speciation.

Neonatal exposure to immunogenic peptides. Differential susceptibility to tolerance induction of helper T cells and B cells reactive to malarial circumsporozoite peptide epitopes.

The effects of neonatal administration of immunogenic peptides on subsequent T and B cell function were tested using defined T and B cell peptide epitopes from the circumsporozoite (CS) protein of the human malaria parasite, Plasmodium falciparum. We observed that neonatal exposure of responder strain mice to either of the two major murine T sites on the CS protein resulted in specific tolerance of both helper and proliferating T cells. One of these T sites, (NANP)n, is also the immunodominant B epitope on the CS protein. We took advantage of this fact to directly compare the effects of neonatal peptide administration on B and T cell function and observed that mice whose helper and proliferating T cells were tolerant to (NANP)n nevertheless produced normal levels of anti-(NANP)n antibodies after immunization with keyhole limpet hemocyanin-(NANP)n. Our results demonstrate differential susceptibility of the Th cells and B cells to toleragens and suggest that self-tolerance to peptide epitopes during the neonatal period reflects predominantly Th cell tolerance.

Disseminated mycobacterium avium complex infection presenting as osteomyelitis in a normal host.

Disseminated Mycobacterium avium complex (MAC) infection presenting as a painful lytic femur lesion with associated fever, night sweats and weight loss occurred in a 45-y-old woman with apparent normal immune function. Surgical drainage and 24 months of medical therapy resulted in a cure.

Recombinant human IL-2 overcomes genetic nonresponsiveness to malaria sporozoite peptides. Correlation of effect with biologic activity of IL-2.

Current malaria vaccine strategies focus on subunit vaccines that contain one or a limited number of malaria Ag. However, there is widespread nonresponsiveness to many of these Ag probably resulting from Ir gene control. Using a congenic mouse model, we demonstrated that human rIL-2 (as an adjuvant) can overcome Ir gene controlled low immune responsiveness to peptide malaria Ag vaccine candidates [R32tet32, R32LR, and Th2R-NP (NANP)5NA] as determined by the antibody response, providing it is emulsified with the Ag during immunization. This effect is not caused by IL-2 merely acting as a foreign protein and stimulating noncognate help; it requires biologic activity of the IL-2, as determined by studying the effect of inactive rIL-2, which has minimal biologic activity but which has retained its antigenicity. IL-2 does not appear to be working by an effect on priming of specific Th, and IL-2 cannot overcome an Ir gene controlled low T cell proliferative response. IL-2 may have a role to play in human vaccine development where a high titer antibody response to a subunit vaccine is required.

Parasite polymorphism present within minimal T cell epitopes of Plasmodium falciparum circumsporozoite protein.

Identification of T cell antigenic sites is critical for antisporozoite malarial vaccine design. Here, we present data that define two minimal functional T cell sites present in an immunogenic domain of the circumsporozoite protein of Plasmodium falciparum. These two sites overlap one another and correlate with polymorphic regions of the molecule. This suggests that these polymorphisms may be a result of pressure from immune T cells.

Human T-cell recognition of the circumsporozoite protein of Plasmodium falciparum: immunodominant T-cell domains map to the polymorphic regions of the molecule.

The definition of human T-cell antigenic sites is important for subunit vaccine development of a peptide immunogen if the goal is to allow antibody boosting during infection or to stimulate antibody-independent T-cell immunity. To identify such sites on the circumsporozoite (CS) protein of Plasmodium falciparum, 29 overlapping synthetic peptides spanning the entire CS protein were made and tested for their ability to stimulate peripheral blood lymphocytes from 35 adults living in a P. falciparum malaria-endemic region of West Africa. Three immunodominant domains were located outside the repetitive region. These domains, however, occurred in the polymorphic regions of the molecule, suggesting that parasite mutation and selection has occurred in response to immune pressure from T cells. Such polymorphism may impose an obstacle for vaccine development.

Human and murine CD4 T cell epitopes map to the same region of the malaria circumsporozoite protein: limited immunogenicity of sporozoites and circumsporozoite protein.

The circumsporozoite (CS) protein is a candidate vaccine antigen for the sporozoite stage in the life cycle of the malaria parasite. Using CS protein purified from recombinant baculovirus-infected cells and a panel of H-2 congenic mice, we are able to demonstrate that this protein is poorly immunogenic in terms of antibody production as a result of Ir gene control. The immune response to the protein is also restricted following immunization with a CS-recombinant vaccinia virus or with sporozoites. Using a panel of overlapping peptides spanning the entire protein, we are able to show that the high responder mice recognize helper T cell epitopes from the same region of the protein as do humans. This region, however, is the polymorphic segment of the protein, which has implications for vaccine development. However, the close overlap of human and murine T cell epitopes demonstrates that murine models may be very useful in epitope mapping and vaccine development for human pathogens. The T cell antigenic regions of this protein fulfil the predictive requirements for the amphipathic helicity algorithm.

Effect of vaccination with 3 recombinant asexual-stage malaria antigens on initial growth rates of Plasmodium falciparum in non-immune volunteers.

A placebo controlled, randomised, double blind trial was conducted in human volunteers to test a mixture of three recombinant Plasmodium falciparum blood stage antigens for its ability to reduce the initial growth rates of parasites. The vaccine contained recombinant MSP2 (3D7 allele), a portion of MSP1 (190LCS.T3) and part of the RESA antigen (C terminal 771 amino acids) in the Montanide ISA 720 adjuvant (SEPPIC). Twelve volunteers received two doses of the vaccine, 6 weeks apart. The five participants in the placebo group received an equivalent volume of the adjuvant emulsion using the same schedule. Antibody responses were low, as has been reported in earlier studies with this combination, while T cell responses were stronger. All the volunteers were challenged with approximately 140 ring infected red cells of the 3D7 cloned line, 4 weeks after the second dose. Parasitaemia was determined once daily from day 4 using a sensitive and quantitative PCR assay. All the volunteers were infected and were treated on day 8, before any developed symptoms. There was no significant difference in initial parasite growth rates between the verum and placebo groups, nor was there any significant correlation between parasite growth rates and any of the measured immunological responses. These results suggest that the formulation tested in this trial did not generate immune responses that were strong enough to reduce parasite growth in naive volunteers.