RESUMO
A photosensitized high-surface area transparent electrode has been employed to increase the short circuit current of a photovoltaic device with a blend of poly(3-hexylthiophene) (P3HT) and (6,6)-phenyl C61 butyric acid methyl ester (PCBM) as the active layer. This is achieved by directly growing ZnO nanowires on indium tin oxide (ITO) film via a physical vapor method. The nanowire surface is then decorated with CdTe quantum dots by pulsed electron-beam deposition (PED). The nanowires alone provided a 20-fold increase in the short circuit current under visible light illumination. This was further increased by a factor of approximately 1.5 by the photosensitization effect of CdTe, which has an optical absorption of up to 820 nm.
RESUMO
Pvs25 is an ookinete surface protein from Plasmodium vivax that is the target of transmission-blocking antibodies. Two immunogenicity trials in rhesus monkeys with a recombinant form of the protein, Pvs25H, were undertaken. Monkeys were vaccinated with Pvs25H adsorbed to Alhydrogel or emulsified in Montanide ISA 720 at 0, 4 and 27 weeks (study 1) or in Montanide ISA 720 at 0 and 18 weeks (study 2) with 1.5 or 15 microg Pvs25H in 0.1 or 0.5 mL of emulsion (four combinations). Immunogenicity was assessed by ELISA and by membrane-feeding experiments using P. vivax-infected blood from human volunteers (studies 1 and 2) or from chimpanzees (study 1). Both vaccine trials generated antibodies that blocked transmission of P. vivax to mosquitoes. Antibody titres and transmission blocking were higher with Montanide ISA 720 than with Alhydrogel in the first trial and with the 15 microg Pvs25H/0.5 mL ISA 720 combination in the second trial.
Assuntos
Anopheles/parasitologia , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Antígenos de Superfície/imunologia , Vacinas Antimaláricas/imunologia , Malária Vivax/imunologia , Plasmodium vivax/imunologia , Adjuvantes Imunológicos , Hidróxido de Alumínio/imunologia , Animais , Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/administração & dosagem , Antígenos de Superfície/administração & dosagem , Feminino , Humanos , Macaca mulatta , Vacinas Antimaláricas/administração & dosagem , Malária Vivax/parasitologia , Malária Vivax/transmissão , Masculino , Manitol/análogos & derivados , Manitol/imunologia , Ácidos Oleicos/imunologia , Plasmodium vivax/crescimento & desenvolvimento , Distribuição Aleatória , Proteínas Recombinantes/imunologiaRESUMO
Plasmodium malariae occurs in various tropical regions throughout the world and causes low, yet significant, levels of morbidity in human populations. One means of studying the ecology and frequency of this parasite is by measuring sporozoite loads in the salivary glands of infected mosquitoes. An effective, species-specific test that can be used to detect the presence of sporozoites in mosquitoes is the circumsporozoite ELISA. The aim of the present study was to standardize the circumsporozoite ELISA for P.malariae, by setting quantification parameters using, as antigen, either a synthetic peptide or extracts of whole sporozoites. The standard quantification curves produced indicated that the assay had a lower threshold of sensitivity of 250 sporozoites in a 50-microl sample, equivalent to about 1250 sporozoites in a mosquito.
Assuntos
Anopheles/parasitologia , Insetos Vetores/parasitologia , Plasmodium malariae/isolamento & purificação , Animais , Anticorpos Monoclonais/imunologia , Antígenos de Protozoários/imunologia , Relação Dose-Resposta Imunológica , Ensaio de Imunoadsorção Enzimática/métodos , Plasmodium malariae/imunologia , Glândulas Salivares/parasitologia , Esporozoítos/isolamento & purificaçãoRESUMO
Malaria therapy reinoculation data were examined for the possible detection of effects attributable to stable individual host-specific factors, through correlation between descriptive variables of first and second infections. Such an effect was demonstrated with respect to the first local maximum of the asexual parasite density, i.e., the density at which a host controls parasite growth. The effect was seen between an individual host's first and second Plasmodium falciparum infection, as well as between an individual host's first malaria infection with P. ovale and second malaria infection with P. falciparum. We give reasons to believe that the main underlying mechanism is individual variation of an innate immune response. The data were also examined for systematic changes from first to second P. falciparum infection, as indicators of acquired immunity. In addition to the well-known reduction in parasite density, the data show the early development of apparent parasite tolerance. We give reasons to interpret the latter as antitoxic immunity.
Assuntos
Anticorpos Antiprotozoários/imunologia , Malária/imunologia , Plasmodium/imunologia , Animais , Interações Hospedeiro-Parasita , Humanos , Malária/terapia , Plasmodium falciparum/imunologiaRESUMO
A retrospective analysis was performed of parasite count data recorded from the first 7 days of blood or mosquito transmitted Plasmodium falciparum infections given for the treatment of neurosyphilis in the USA before 1963. The objective of this study was to characterize initial growth dynamics before host defences have significant effects on the infecting parasite population. Of the 328 patients' data available for analysis, 83 were excluded because they had received anti-malarial treatment during the first 7 days of the patent infection. Nonlinear mixed effects modelling was performed to estimate the parameters of interest; 'parasite multiplication rate per 48 h' (PMR), and length of the parasite life-cycle (periodicity). The parasitaemia versus time profiles showed great variability between patients. The mean population estimate of 'PMR' was approximately 8, and was highly dependent on the P. falciparum 'strain'. PMR also varied significantly between patients with a 90% prediction interval varying from 5.5 to 12.3-fold. Both intrinsic parasite multiplication rate (an intrinsic virulence determinant), and host susceptibility and defence contribute to expansion of the parasite biomass and thus disease severity in falciparum malaria.
Assuntos
Malária Falciparum/sangue , Malária Falciparum/parasitologia , Modelos Estatísticos , Plasmodium falciparum/crescimento & desenvolvimento , Animais , Interações Hospedeiro-Parasita , Humanos , Parasitemia/sangue , Parasitemia/parasitologia , Periodicidade , Dinâmica Populacional , Estudos RetrospectivosRESUMO
Transmission-blocking vaccines against malaria parasites target molecules expressed by sexual stage parasites to elicit antibodies that prevent the infection of the mosquito vector. Pvs25 and Pvs28, expressed on the surface of ookinetes, are potential candidates for such a vaccine and induce antibodies that block the infectivity of Plasmodium vivax in immunized animals. To improve the ability to induce transmission-blocking antibodies, Pvs25 and Pvs28 were produced as a single fusion protein by the yeast Saccharomyces cerevisiae. Mice immunized with a low dose of the chimeric molecule (Pvs25-28) developed higher antibody responses compared with mice immunized with either Pvs25 or Pvs28. In membrane feeding assays, both anti-Pvs25-28 and anti-Pvs25 antisera had similarly potent transmission-blocking activities (and both were much greater than anti-Pvs28). Furthermore, serum from mice simultaneously immunized with both Pvs25 and Pvs28, or serum mixtures of anti-Pvs25 alone and anti-Pvs28 alone did not enhance the efficacy over anti-Pvs25 serum alone, demonstrating that there is no synergism in the ability to block transmission of P. vivax between anti-Pvs25 and anti-Pvs28 antibodies.
Assuntos
Anticorpos Antiprotozoários/biossíntese , Antígenos de Protozoários/administração & dosagem , Vacinas Antimaláricas/administração & dosagem , Plasmodium vivax/imunologia , Animais , Antígenos de Protozoários/genética , Sequência de Bases , Culicidae/parasitologia , DNA de Protozoário/genética , Sinergismo Farmacológico , Feminino , Imunização , Insetos Vetores/parasitologia , Vacinas Antimaláricas/genética , Malária Vivax/imunologia , Malária Vivax/prevenção & controle , Malária Vivax/transmissão , Camundongos , Plasmodium vivax/genética , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genéticaRESUMO
Plasmodium falciparum malaria is one of mankind's main killers. Part of the parasite's life-cycle is spent in human blood, mainly as asexual stages. A fraction of the asexual parasites develops into gametocytes (gamete precursors) while sequestered in deep tissues. After re-entering the circulation, gametocytes can be picked up by a mosquito to continue the parasite's life-cycle. We present estimates of the conversion probability from asexual parasites to circulating gametocytes and of the gametocytes' sequestration and circulation times, obtained for the first time by fitting a dynamic model to individual patients' histories (daily records of 113 neurosyphilitic patients undergoing malariatherapy). The model assumes that the conversion probability can vary among the successive waves of asexual parasitaemia of a patient, and that gametocytes die at an age-dependent rate which increases under high asexual parasite densities. On average, 1 gametocyte per 156 asexual parasites (range 7.4-3700) is produced. The most remarkable findings are the large individual variation of conversion probabilities and circulation times, the average gametocyte circulation time of 6.4 days (range 1.3-22.2 days) which is more than twice the currently accepted value, and the large variation of conversion probabilities among successive waves of asexual parasitaemia without any particular time pattern. The latter finding could be explained by an association between conversion probability and variation of PfEMP1.
Assuntos
Gametogênese/fisiologia , Modelos Biológicos , Plasmodium falciparum/crescimento & desenvolvimento , Animais , Humanos , Estágios do Ciclo de Vida/fisiologia , Malária Falciparum/terapia , Reprodução Assexuada/fisiologiaRESUMO
Plasmodium coatneyi has adapted well to experimental studies with Macaca mulatta monkeys and Anopheles dirus mosquitoes. Studies were made to determine 1) the course of asexual parasitemia, 2) periods when infective gametocytes were produced, 3) the laboratory-reared mosquitoes susceptible to infection, 4) the mosquito most capable of transmitting the infection to monkeys via bite, 5) the pattern of recrudescence, and 6) the prepatent periods following the bites of infected An. dirus mosquitoes. The period when infective gametocytes are produced is concentrated primarily in the first week when parasitemia exceeds 1,000/microl. Mosquitoes were more heavily infected on days when the asexual parasite counts were highest. Gametocyte counts were generally low. Mature forms of the parasite markedly sequestered giving a pattern of high-low periodicity. Anopheles dirus and An. freeborni mosquitoes were nearly equal in terms of their ability to support oocyst development. Other species (An. stephensi, An. maculatus, and An. gambiae.) were less supportive. High sporozoite densities in the salivary glands were frequently produced in An. dirus and sporozoite transmission was obtained via the bites of these mosquitoes after 12-18 days of extrinsic incubation. Prepatent periods ranged from 10 to 15 days. The presence of frequent parasitic recrudescences suggests mechanisms similar to that seen in human infections with P. falciparum. It is proposed that P. coatneyi in M. mulatta monkeys can be a suitable model for studies on cerebral pathology, vaccine efficacy, and the testing of antimalarial drugs.
Assuntos
Anopheles/parasitologia , Modelos Animais de Doenças , Insetos Vetores/parasitologia , Macaca mulatta/parasitologia , Malária/transmissão , Plasmodium/patogenicidade , Animais , Humanos , Malária/parasitologia , Malária/patologia , Parasitemia/parasitologia , PeriodicidadeRESUMO
We examine the dynamics of parasitemia, fever, and gametocytemia reflected in the preintervention charts of 180 malaria-naive U.S. neurosyphilis patients infected with the USPHS strain of Plasmodium malariae, for malariatherapy, focusing on the 84 charts for which more than 35 days of patency preceded intervention and daily records encompassed 92% or more of the duration of each infection. Inoculum size did not influence any outcome variable. Fevers (days with temperatures > or =101 F) followed patterns that fit recognized brood structures more often than did our approximations of merogony cycles (via local peaks in parasitemia), but neither closely fit textbook quartan patterns. There were no discernable patterns in gametocytemia. Successful transmission to mosquitoes increased following subcurative drug treatment but did not depend on detectable gametocytemia.
Assuntos
Febre/parasitologia , Malária/parasitologia , Parasitemia/parasitologia , Plasmodium malariae/fisiologia , Animais , Humanos , Prontuários Médicos , Estudos Retrospectivos , Fatores de TempoRESUMO
Chloroquine (CQ)-resistant Plasmodium vivax malaria was first reported 12 years ago, nearly 30 years after the recognition of CQ-resistant P. falciparum. Loss of CQ efficacy now poses a severe problem for the prevention and treatment of both diseases. Mutations in a digestive vacuole protein encoded by a 13-exon gene, pfcrt, were shown recently to have a central role in the CQ resistance (CQR) of P. falciparum. Whether mutations in pfcrt orthologues of other Plasmodium species are involved in CQR remains an open question. This report describes pfcrt homologues from P. vivax, P. knowlesi, P. berghei, and Dictyostelium discoideum. Synteny between the P. falciparum and P. vivax genes is demonstrated. However, a survey of patient isolates and monkey-adapted lines has shown no association between in vivo CQR and codon mutations in the P. vivax gene. This is evidence that the molecular events underlying P. vivax CQR differ from those in P. falciparum.
Assuntos
Cloroquina/farmacologia , Chaperonas Moleculares/genética , Plasmodium/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Códon , Dictyostelium/química , Dictyostelium/genética , Resistência a Medicamentos , Humanos , Dados de Sequência Molecular , Mutação , Testes de Sensibilidade Parasitária , Plasmodium/química , Plasmodium/genética , Alinhamento de SequênciaRESUMO
A new mathematical model of Plasmodium falciparum asexual parasitaemia is formulated and fitted to 35 malaria therapy cases making a spontaneous recovery after primary inoculation. Observed and simulated case-histories are compared with respect to 9 descriptive statistics. The simulated courses of parasitaemia are more realistic than any previously published. The model uses a discrete time-step of 2 days. Its realistic behaviour was achieved by the following combination of features (i) intra-clonal antigenic variation, (ii) large variations of the variants' baseline growth rate, depending on both variant and case, (iii) innate autoregulation of the asexual parasite density, variable among cases, (iv) acquired variant-specific immunity and (v) acquired variant-transcending immunity, variable among cases. Aspects of the model's internal behaviour, concerning variant dynamics, as well as the respective contributions of the three control mechanisms (iii) - (v), are displayed. Some implications for pathogenesis and control are discussed.
Assuntos
Malária Falciparum/parasitologia , Modelos Biológicos , Parasitemia/parasitologia , Plasmodium falciparum/fisiologia , Animais , Antimaláricos/uso terapêutico , Humanos , Malária Falciparum/tratamento farmacológico , Parasitemia/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacosRESUMO
The mosquito midgut plays a central role in the sporogonic development of malaria parasites. We have found that polyclonal sera, produced against mosquito midguts, blocked the passage of Plasmodium falciparum ookinetes across the midgut, leading to a significant reduction of infections in mosquitoes. Anti-midgut mAbs were produced that display broad-spectrum activity, blocking parasite development of both P. falciparum and Plasmodium vivax parasites in five different species of mosquitoes. In addition to their parasite transmission-blocking activity, these mAbs also reduced mosquito survivorship and fecundity. These results reveal that mosquito midgut-based antibodies have the potential to reduce malaria transmission in a synergistic manner by lowering both vector competence, through transmission-blocking effects on parasite development, and vector abundance, by decreasing mosquito survivorship and egg laying capacity. Because the intervention can block transmission of different malaria parasite species in various species of mosquitoes, vaccines against such midgut receptors may block malaria transmission worldwide.
Assuntos
Anopheles/imunologia , Anopheles/parasitologia , Plasmodium falciparum/fisiologia , Plasmodium vivax/fisiologia , Animais , Anopheles/anatomia & histologia , Anopheles/crescimento & desenvolvimento , Anticorpos Monoclonais/imunologia , Western Blotting , Humanos , Soros Imunes/imunologia , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Malária Vivax/parasitologia , Malária Vivax/transmissão , Camundongos , Pan troglodytes/imunologia , Plasmodium falciparum/citologia , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium vivax/citologia , Plasmodium vivax/crescimento & desenvolvimento , Estômago/imunologia , Taxa de SobrevidaRESUMO
We examined geographically distinct isolates of Plasmodium vivax and categorized them according to developmental success in Anopheles albimanus. We found that parasites from Central America and Colombia form a group distinct from those of Asia. New World isolates have a distinct chromosomal translocation and an episomal variation in the open reading frame (ORF) 470 DNA sequence that distinguishes them from the other isolates tested. Old World types of P. vivax were introduced into the Americas, and a remnant of this lineage remains in P. simium. It is indistinguishable from Old World P. vivax to the extent determinable by using our encoded markers and the examination of its developmental pattern in mosquitoes. The cohesive characteristics that separate types of P. vivax are predictors of range and potential for transmission and hence require taxonomic distinction.
Assuntos
Plasmodium vivax/classificação , Sequência de Aminoácidos , Animais , Anopheles/parasitologia , Sequência de Bases , Marcadores Genéticos , Dados de Sequência Molecular , Fases de Leitura Aberta , Plasmodium vivax/genética , Plasmodium vivax/isolamento & purificação , RNA Ribossômico/genéticaRESUMO
A strain of Plasmodium vivax from India was adapted to develop in splenectomized Saimiri boliviensis, Aotus lemurinus griseimembra, A vociferans, A. nancymai, A. azarae boliviensis, hybrid Aotus monkeys, and splenectomized chimpanzees. Infections were induced via the inoculation of sporozoites dissected from the salivary glands of Anopheles stephensi and An. dirus mosquitoes to 12 Aotus and 8 Saimiri monkeys; transmission via the bites of infected An. stephensi was made to 1 Aotus monkey and 1 chimpanzee. The intravenous passage of infected erythrocytes was made to 9 Aotus monkeys and 4 chimpanzees. Gametocytes in 13 Aotus monkeys and 4 chimpanzees were infectious to mosquitoes. Infection rates were markedly higher in mosquitoes fed on chimpanzees. PCR studies on 10 monkeys injected with sporozoites revealed the presence of parasites before their detection by microscopic examination. The India VII strain of P. vivax develops in Aotus and Saimiri monkeys and chimpanzees following the injection of parasitized erythrocytes, or sporozoites, or both. The transmission rate via sporozoites to New World monkeys of approximately 50% may be too low for the testing of sporozoite vaccines or drugs directed against the exoerythrocytic stages. However, the strain is highly infectious to commonly available laboratory-maintained anopheline mosquitoes. Mosquito infection is especially high when feedings are made with gametocytes from splenectomized chimpanzees.
Assuntos
Adaptação Biológica , Anopheles/parasitologia , Cebidae/parasitologia , Malária Vivax/veterinária , Doenças dos Macacos/parasitologia , Pan troglodytes/parasitologia , Plasmodium vivax/classificação , Animais , Aotidae/parasitologia , Índia , Insetos Vetores/parasitologia , Malária Vivax/diagnóstico , Doenças dos Macacos/diagnóstico , Parasitemia/diagnóstico , Plasmodium vivax/patogenicidade , Saimiri/parasitologia , EsplenectomiaRESUMO
Study of arterial blood flow dynamics improves our understanding of the development of cardiovascular diseases such as atherosclerosis. The transport and accumulation of macromolecules in the arterial wall can be influenced by local fluid mechanics. We used numeric simulations to investigate such transport in a T-junction model. Presumably an in vitro experiment would consist of gel segments inserted in the walls of a mechanical flow T-junction model near branch points where separation and recirculation zones are expected. The transport of low density lipoprotein (LDL) was investigated theoretically at these sites in a two dimensional numeric T-branch model. In the numeric model, the hydraulic conductivity of the porous gel wall segments was varied for a fixed species diffusivity to provide simulations with wall transmural Peclet numbers ranging from 0.3 to 30. Steady state flow patterns in the lumen of the two dimensional T-branch were simulated at Reynolds numbers of 250 and 500, using the software package FIDAP 7.61 to implement the finite element method. The simulations demonstrated that wall Peclet numbers greater than 1.0 were needed to achieve species concentration gradients within the wall that varied in the axial direction, thereby reflecting the influence of disturbed flow and pressure patterns in the lumen. As expected, the transmural concentration gradients were steeper when convection predominated. Blood flow in the lumen can influence the distribution of macromolecules in the arterial wall and needs to be investigated for the relevance to atherosclerosis.
Assuntos
Artérias/metabolismo , Lipoproteínas/metabolismo , Modelos Cardiovasculares , Arteriosclerose/etiologia , Transporte Biológico Ativo , Velocidade do Fluxo Sanguíneo , Hemodinâmica , Humanos , Lipoproteínas/sangue , Lipoproteínas LDL/sangue , Lipoproteínas LDL/metabolismo , SoftwareRESUMO
Transmission-blocking vaccines are one strategy for controlling malaria, whereby sexual-stage parasites are inhibited from infecting mosquitoes by human antibodies. To evaluate whether the recently cloned Plasmodium vivax proteins Pvs25 and Pvs28 are candidates for a transmission-blocking vaccine, the molecules were expressed in yeast as secreted recombinant proteins. Mice vaccinated with these proteins adsorbed to aluminum hydroxide developed strong antibody responses against the immunogens, although for Pvs28, this response was genetically restricted. Antisera against both recombinant Pvs25 and Pvs28 recognized the corresponding molecules expressed by cultured sexual-stage parasites isolated from patients with P. vivax malaria. The development of malaria parasites in mosquitoes was completely inhibited when these antisera were ingested with the infected blood meal. Pvs25 and Pvs28, expressed in Saccharomyces cerevisiae, are as yet the only fully characterized transmission-blocking vaccine candidates against P. vivax that induce such a potent antiparasite response.
Assuntos
Anticorpos Antiprotozoários/uso terapêutico , Antígenos de Protozoários/imunologia , Antígenos de Superfície/imunologia , Culicidae/parasitologia , Vacinas Antimaláricas/imunologia , Plasmodium vivax/imunologia , Sequência de Aminoácidos , Animais , Antígenos de Protozoários/genética , Antígenos de Superfície/genética , Clonagem Molecular , Soros Imunes/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Pan troglodytes , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificaçãoRESUMO
In this paper, we investigate the transition of asexual blood stages of P. falciparum to gametocytes. The study is based on daily data, collected from 262 individual courses of parasitaemia. We propose several mathematical models that follow biological reasoning. The models are fitted with maximum likelihood and are compared with each other. The models differ in the assumptions made about the mortality of circulating gametocytes and about the transition rate of the asexual parasites. Gametocyte mortality is modelled as being (i) constant over time, (ii) linearly increasing over time, (iii) linearly increasing over gametocyte age, and (iv) exponentially increasing over gametocyte age, respectively. The transition rate is either kept constant per patient or piecewise constant within intervals that correspond to waves of asexual parasitaemia which are assumed to be caused by different Pf(emp1)-variants. According to likelihood ratio tests, the models with age-dependent mortality rate and wave-dependent transition rates are superior to the models with constant transition rate and/or constant or time-dependent mortality rate. The best fits are reached for models with exponentially increasing (Gompertz-type) mortality. Furthermore, an impact of high asexual parasite densities on the survival of gametocytes, interpreted as a cytokine-mediated effect, is evident in some cases.
Assuntos
Malária Falciparum/patologia , Parasitemia/patologia , Plasmodium falciparum/crescimento & desenvolvimento , Animais , Interações Hospedeiro-Parasita , Humanos , Modelos BiológicosRESUMO
BACKGROUND: Two practical color vision tests were developed and validated for use in screening Air Traffic Control Specialist (ATCS) applicants for work at en route center or terminal facilities. The development of the tests involved careful reproduction/simulation of color-coded materials from the most demanding, safety-critical color task performed in each type of facility. METHODS: The tests were evaluated using 106 subjects with normal color vision and 85 with color vision deficiency. The en route center test, named the Flight Progress Strips Test (FPST), required the identification of critical red/black coding in computer printing and handwriting on flight progress strips. The terminal option test, named the Aviation Lights Test (ALT), simulated red/green/white aircraft lights that must be identified in night ATC tower operations. Color-coding is a non-redundant source of safety-critical information in both tasks. RESULTS: The FPST was validated by direct comparison of responses to strip reproductions with responses to the original flight progress strips and a set of strips selected independently. Validity was high; Kappa = 0.91 with original strips as the validation criterion and 0.86 with different strips. The light point stimuli of the ALT were validated physically with a spectroradiometer. The reliabilities of the FPST and ALT were estimated with Chronbach's alpha as 0.93 and 0.98, respectively. CONCLUSIONS: The high job-relevance, validity, and reliability of these tests increases the effectiveness and fairness of ATCS color vision testing.
Assuntos
Medicina Aeroespacial , Aviação , Defeitos da Visão Cromática/diagnóstico , Avaliação da Deficiência , Saúde Ocupacional , Seleção Visual/métodos , Seleção Visual/normas , Adolescente , Adulto , Defeitos da Visão Cromática/classificação , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
A vaccine trial was conducted with rhoptry-associated proteins 1 and 2 (RAP1 and RAP2) of Plasmodium falciparum in Saimiri boliviensis monkeys to compare the ability of parasite-derived (PfRAP1 and 2) and recombinant proteins (rRAP1 and 2) to induce protective immune responses and to find adjuvants suitable for use in humans. Eight groups of 6 monkeys each were immunized with parasite-derived or recombinant RAP1 and 2 with Freund's complete adjuvant (FCA) followed by Freund's incomplete adjuvant (FIA), Montanide ISA720 adjuvant, or CRL1005 adjuvant. Recombinant RAP1 and RAP2 were also administered separately, with Montanide ISA720. After 3 immunizations, monkeys were challenged by iv inoculation of 50,000 parasites of the Uganda Palo Alto strain of P. falciparum. Of the animals vaccinated using FCA/FIA, 1 of 6 control monkeys, 3 of 6 immunized with PfRAP1 and 2, and 2 of 6 with rRAP1 and 2 did not require drug treatment. Of the monkeys vaccinated with Montanide ISA720 adjuvant, 0 of the 6 control monkeys, 2 of 6 immunized with RAP1 and 2, 1 of 6 immunized with rRAP1, and 4 of 6 immunized with RAP2 did not require drug treatment. Two of 6 monkeys immunized with PfRAP1 and 2 with CRL1005 did not require treatment. All groups receiving RAP1, RAP2, or both had a significant decrease in initial parasite multiplication rates and there was a significant negative correlation between anti-RAP2 antibody and multiplication rates. Animals were rechallenged with the homologous parasite 126 days after the first challenge. Of the monkeys that did not require drug treatment after the first challenge, none developed detectable parasitemia following rechallenge.
Assuntos
Vacinas Antimaláricas , Malária Falciparum/prevenção & controle , Parasitemia/prevenção & controle , Plasmodium falciparum/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antiprotozoários/biossíntese , Anticorpos Antiprotozoários/sangue , Feminino , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/efeitos adversos , Vacinas Antimaláricas/imunologia , Masculino , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Proteínas Recombinantes/imunologia , SaimiriRESUMO
The spread of chloroquine-resistant Plasmodium vivax from Papua New Guinea and Indonesia poses a serious health threat to areas of Southeast Asia where this species of malaria parasite is endemic. A strain of P. vivax from Indonesia was adapted to develop in splenectomized Aotus lemurinus griseimembra, Aotus vociferans, Aotus nancymai, and Saimiri boliviensis monkeys. Transmission to splenectomized Saimiri monkeys was obtained via sporozoites. Chemotherapeutic studies indicated that the strain was resistant to chloroquine and amodiaquine while sensitive to mefloquine. Infections of chloroquine-resistant P.vivax in New World monkeys should be useful for the development of alternative treatments.