RESUMO
Genetically determined variation in host capacity to express resistance to a given parasite plays a major role in determining the outcome of infection. It can be assumed that the same is true of variation in parasites, but very much less is known of its influence on the host-parasite relationship. Phenotypic and genotypic variation within species of intestinal worms is now well documented, detailed studies having been made of parasites such as Ascaris in humans and trichostrongyles in domestic animals. However, the extent to which this variation affects the course of infection or the host immune response in these hosts is limited. Of the nematodes used as experimental models in laboratory rodents, detailed data on phenotypic or genotypic variation are limited to Strongyloides and Trichinella. Parasite variation is known to be subject to host-mediated selection, the emergence of anthelmintic resistance being a good example. Repeated passage has been used to select lines of parasite that survive in abnormal hosts or which show adaptation to host immunity. Experimental studies with Trichinella genotypes in mice have demonstrated the extent to which parasite variation influences the nature and degree of the host's immune and inflammatory responses, the complex interplay between immunogenicity and pathogenicity influencing both partners in the relationship. Recent studies with isolates of Trichuris muris have shown how parasite variation influences the capacity of mice to express the T helper cell responses necessary for resistance. Molecular differences between T. muris isolates have been shown in their excreted/secreted products as well as at the level of their DNA. Knowledge of the functional consequences of parasite variation will add to our understanding of host-parasite evolution as well as providing a rational basis for predicting the outcome of controls strategies that rest on the improvement of host resistance through vaccination or selective breeding.
Assuntos
Variação Genética , Enteropatias Parasitárias/imunologia , Animais , Resistência a Medicamentos/genética , Genótipo , Interações Hospedeiro-Parasita/genética , Interações Hospedeiro-Parasita/imunologia , Humanos , Imunidade Celular , Enteropatias Parasitárias/parasitologia , Camundongos , Fenótipo , Seleção Genética , Trichinella/genética , Trichinella/imunologia , Trichinella/patogenicidade , Triquinelose/imunologia , Triquinelose/parasitologia , Tricuríase/imunologia , Tricuríase/parasitologia , Trichuris/genética , Trichuris/imunologiaRESUMO
An autochthonous case of human onchocerciasis was reported 13 years ago in the town of Minaçu, northern Goiás (Brazil), but a subsequent survey of the population using the traditional technique of examining skin biopsies with the light microscope failed to detect other cases. Recent surveys using more sensitive diagnostic techniques (serodiagnosis, DNA probes, Mazzotti test) that are detailed in this paper revealed the presence of other cases of the disease in Minaçu, the nearby town of Formoso and at the Buracão gold mine near Paranã. The data show that transmission of the disease has occurred to local people living in town and on farms and that gold miners (garimpeiros) are a likely source of infection.
Assuntos
Onchocerca volvulus , Oncocercose/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Brasil/epidemiologia , Sondas de DNA , Feminino , Humanos , Masculino , Microfilárias/isolamento & purificação , Pessoa de Meia-Idade , Oncocercose/diagnóstico , Oncocercose/transmissão , Testes Sorológicos , Pele/parasitologia , Topografia MédicaRESUMO
A recently described hyperendemic onchocerciasis area, located in the Unturán Mountains (between the Siapa and Orinoco basins) of southern Venezuela was studied using a cocktail of 3 low molecular weight onchocercal recombinant antigens (OvMBP/10, OvMBP/11, and OvMBP/29). The resulting seroepidemiological data were compared with those from a hypoendemic community (Altamira) situated in the northern coastal mountain range. Parasitological (skin biopsy) and serological (enzyme-linked immunosorbent assay, ELISA) methods for the specific diagnosis of Onchocerca volvulus in these 2 very different endemic areas were, respectively, 88% and 96% sensitive in Unturán, and 57% and 91% sensitive in Altamira. The mean microfilarial load, the mean optical density (OD), and the seropositivity rates all increased significantly with age in both communities. The serological variables (mean OD and prevalence of anti-O. volvulus antibodies) were both significantly higher in Unturán than in Altamira for children and young adults (aged < 25 years), although above this age no differences between communities were detected. Seroprevalence had already reached 50% in the under 15 year-olds examined at Unturán but was just 5% at Altamira for the same age-class. The prevalence of specific antibodies (mainly a marker of exposure to risk of infection) exceeded 85% in the remaining age-categories at the hyperendemic area. This is in agreement with the high community microfilarial load recorded in Unturán (> 20 mf/mg) and the presence of sclerosing keratitis and hanging groin, suggesting that onchocerciasis is a public health problem in this community. The ELISA test used here, based on a cocktail of 3 low molecular weight onchocercal recombinant antigens, appears, therefore, to constitute a practical tool for the description of endemicity levels in remote areas, particularly given the fact that finger-prick blood samples are routinely taken from children in the Upper Orinoco region for surveys of malaria incidence. Such studies could aid in defining the true extent of the Amazon focus (still unknown) and providing priority indicators for the selection of communities where onchocerciasis control programmes should be implemented.
Assuntos
Antígenos de Helmintos/análise , Doenças Endêmicas , Oncocercose/epidemiologia , Adulto , Distribuição por Idade , Animais , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Onchocerca volvulus/imunologia , Oncocercose/imunologia , Oncocercose/parasitologia , Oncocercose/transmissão , Prevalência , Sensibilidade e Especificidade , Estudos Soroepidemiológicos , Venezuela/epidemiologiaRESUMO
OBJECTIVE AND METHOD: To compare the utility of an ELISA using 3 recombinant antigens with that of the skin biopsy to estimate incidence of infections in a sentinel cohort of individuals living in an endemic community in southern Mexico during a set of 11 subsequent ivermectin treatments. RESULTS: The apparent community prevalence of infection and microfilarial skin infection before and after 11 treatments with ivermectin plus nodulectomy were 78% and 13%, and 0.68 mf/mg and 0.04 mf/mg, respectively, as measured by skin biopsy. Of a group of 286 individuals participating in all surveys, a sentinel cohort of 42 mf and serologically negative individuals had been followed since 1994. The annual percentage of individuals becoming positive in this cohort was 24% (10/42), 28% (9/33), 0%, and 4.3% (1/23) in 1995, 1996, 1997 and 1998, respectively. Likewise, the incidence in children 5 years and under (n = 13) within this sentinel cohort was 15% (2/13), 18% (2/11), 0% and 11% (1/9), respectively. All individuals became positive to both tests simultaneously, indicating that seroconversion assessed infection incidence as accurately as skin biopsy in the sentinel group. CONCLUSION: Incidence monitoring of a sentinel cohort provides an estimation of the parasite transmission in the community; it is less costly than massive sampling, and a finger prick blood test might be more acceptable in some communities.
Assuntos
Ensaio de Imunoadsorção Enzimática , Filaricidas/uso terapêutico , Ivermectina/uso terapêutico , Onchocerca volvulus/isolamento & purificação , Oncocercose/tratamento farmacológico , Oncocercose/transmissão , Adolescente , Adulto , Animais , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/imunologia , Antiparasitários , Criança , Pré-Escolar , Estudos de Coortes , Doenças Endêmicas , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , México/epidemiologia , Microfilárias/efeitos dos fármacos , Microfilárias/isolamento & purificação , Onchocerca volvulus/efeitos dos fármacos , Onchocerca volvulus/imunologia , Oncocercose/epidemiologia , Oncocercose/parasitologia , Proteínas Recombinantes/imunologia , Pele/parasitologia , Dermatopatias Parasitárias/parasitologia , Dermatopatias Parasitárias/transmissãoRESUMO
Detection of Onchocerca volvulus larvae in vector populations is of prime importance in the assessment of the effectiveness of onchocerciasis control programmes. Traditionally, detection of larvae is attained by the dissection of flies, but this time-consuming method cannot easily discriminate between species of Onchocerca. The genome of all Onchocerca species has a unique 150 bp repeat, which can be amplified by PCR, and O. volvulus-specific DNA probes can detect these products by Southern blot (SB). This study optimizes a PCR/SB assay, and compares it with fly dissection to estimate the prevalence (p) and intensity of infection (m) in the local vector population of a Mexican community that has become hypoendemic as a result of 7 years of treatment with ivermectin and nodulectomy. The PCR detected 1 infected fly in a pool of 99 uninfected flies, but the optimal pool size was 50 flies. At the community level, 1 out of 10,550 flies was positive (p = 0.0095%, 95% confidence intervals CI = 0.00024-0.05280%; m = 0.00027 larvae/parous fly, CI = -0.00026-0.00081) by PCR, and 4 out of 10,772 flies (p = 0.0371%, CI = 0.01012-0.09505%; m = 0.00107 larvae/parous fly, 95% CI = 0.00002-0.00212) by dissection (observed m = 0.0005). Both methods produce statistically similar estimates of the prevalence and intensity, indicating that pool screening is a viable alternative for entomological surveillance in areas where the intensity of transmission is becoming extremely low as a result of control interventions.
Assuntos
Doenças Endêmicas , Insetos Vetores/parasitologia , Onchocerca volvulus/isolamento & purificação , Oncocercose/epidemiologia , Reação em Cadeia da Polimerase , Simuliidae/parasitologia , Animais , Southern Blotting , DNA de Helmintos/análise , Dissecação , Feminino , Filaricidas/uso terapêutico , Insetos Vetores/fisiologia , Ivermectina/uso terapêutico , México/epidemiologia , Onchocerca volvulus/genética , Oncocercose/parasitologia , Oncocercose/transmissão , Prevalência , Simuliidae/fisiologiaAssuntos
Animais , Adolescente , Antígenos de Helmintos/imunologia , Criança , Células Cultivadas , Hanseníase/imunologia , Hanseníase/sangue , Interferon gama/biossíntese , /biossíntese , Leucócitos Mononucleares/imunologia , Mycobacterium leprae/imunologia , Mycobacterium tuberculosis/imunologia , Onchocerca volvulus/imunologia , Oncocercose/imunologia , Oncocercose/sangue , Pré-Escolar , Tuberculina/imunologia , Tuberculose/imunologia , Tuberculose/sangueRESUMO
Persons putatively immune (PI) to Onchocerca volvulus (Ov) infection were identified in Ecuador on the basis of epidemiologic, clinical, and parasitologic findings. Immune responses of PI subjects to a recombinant onchocercal protein, OvMBP20/11, were determined and compared with those of a comparable infected (INF) group from the same Ov-endemic area. PI subjects had significantly less antibody reactivity to this molecule; however, not all INF subjects had an antibody response. IgG1 and IgG4 were the predominant IgG subclasses induced to this molecule, and the amount of IgG1 produced was the only significant difference between the PI and INF groups. In contrast to the antibody responses, proliferative responses to OvMBP20/11 were significantly higher in PI than in INF subjects. Cytokine analysis of peripheral blood mononuclear cell culture supernatants revealed that INF subjects produced significantly more interleukin-10 in response to OvMBP20/11 than did PI subjects. This antigen induced few other cytokines, and there were no differences between study groups.
Assuntos
Antígenos de Helmintos/imunologia , Glicoproteínas/imunologia , Onchocerca volvulus/imunologia , Oncocercose/imunologia , Animais , Anticorpos Anti-Helmínticos/biossíntese , Anticorpos Anti-Helmínticos/sangue , Formação de Anticorpos , População Negra , Equador , Humanos , Imunidade Celular , Imunidade Inata , Imunoglobulina G/biossíntese , Imunoglobulina G/sangue , Imunoglobulina G/classificação , Indígenas Sul-Americanos , Ativação Linfocitária , Proteínas Recombinantes/imunologiaRESUMO
Isotype/subclass-specific antibody responses to adult Onchocerca volvulus extract (OvAg) were assessed by both ELISA and immunoblotting for a group of putatively immune individuals (PIs, n = 29) from a hyperendemic area in Ecuador and for a group of infected individuals (INFs, n = 470) from the same regions. As a group, the PIs have been previously shown to possess lower levels of OvAg specific IgG1, IgG2, IgG3 and IgG4 than INF's but semi-quantitative analysis revealed that the relative proportions of these subclasses differs between the two groups. The IgG of the PI group contained a higher proportion of IgG3 and a lower proportion of IgG4 than the INF group. The frequency distribution of IgG3 responses was similar for the PI and INF groups. The frequency distributions for IgG1, IgG4 and IgE were significantly different between the PI and INF groups. A subgroup of the PIs were identified from frequency distributions and multivariate plots of individual isotype responses as having antibody responses (mainly IgG4) possibly indicative of cryptic infection. High IgE responses were exclusive to INF individuals, and a rare response type of high IgG3 with negligible levels of other isotypes/subclasses was seen only in the PI group. However, the majority of the PIs had negligible responses for all antibody classes. Immunoblots demonstrated no obvious differences in qualitative recognition between the PIs and INFs.
Assuntos
Anticorpos Anti-Helmínticos/imunologia , Isotipos de Imunoglobulinas/imunologia , Onchocerca volvulus/imunologia , Oncocercose/imunologia , Adulto , Animais , Antígenos de Helmintos/imunologia , Equador/epidemiologia , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Humanos , Imunidade , Immunoblotting , Imunoglobulina G/análise , Análise Multivariada , Oncocercose/epidemiologiaRESUMO
The prevalence of IgG antibodies to three recombinant O. volvulus antigens, OvMBP/10, OvMBP/11 and OvMBP/29 was determined in a group of 94 microfilaria positive (mf+) individuals resident in the hyperendemic onchocercal area of Esmeraldas Province, Ecuador. Clone OvMBP/11 was the antigen most frequently recognized by patients sera followed by OvMBP/10 and OvMBP/29. When a cocktail of the three recombinant antigens was used the proportion of positive sera increased to 100%. Antibody responses to the fusion partner maltose binding protein (MBP) were low in comparison with those to the cloned antigens and no correlation of responses between individual antigens was observed. The relative level of antibody response to each of the clones in the cocktail varied between individuals. The distribution of IgG responses to OvMBP/11 was bimodal and those to OvMBP/29 and OvMBP/10 were positively and negatively skewed, respectively. When the three recombinant antigens were used in combination this variation was minimized and the pattern of responses showed a normal distribution as was also seen to crude O. volvulus antigen. The cocktail of recombinants thus offers excellent diagnostic sensitivity in combination with the parasite specificity demonstrated previously.
Assuntos
Anticorpos Anti-Helmínticos/análise , Antígenos de Helmintos/imunologia , Imunoglobulina G/análise , Onchocerca volvulus/imunologia , Oncocercose/imunologia , Adolescente , Adulto , Idoso , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteínas de Transporte/imunologia , Equador/epidemiologia , Feminino , Humanos , Masculino , Proteínas Ligantes de Maltose , Pessoa de Meia-Idade , Dados de Sequência Molecular , Oncocercose/epidemiologia , Proteínas Recombinantes/imunologiaRESUMO
The existence of immunity to Onchocerca volvulus (Ov) infection is suggested by the presence of uninfected persons in hyperendemic areas. A major barrier to the study of immunity has been the correct identification of putatively immune (PI) subjects. To identify a PI group in a hyperendemic area in Ecuador, clinical and epidemiologic information was combined with a polymerase chain reaction (PCR)-based assay identifying Ov DNA in skin snips and a recombinant antigen-based ELISA. Comparison of immune responses revealed that PI subjects had significantly lower levels of Ov-specific IgG, IgG subclasses, and IgE than infected (INF) subjects. Female subjects were significantly more likely to be PI than male subjects, and INF female subjects had significantly lower levels of Ov-specific IgG, IgG1, and IgG3 than INF male subjects. Thus, the use of molecular-based techniques has helped to define more precisely the PI state in onchocerciasis.