RESUMO
BACKGROUND: Antibody responses to sand fly saliva have been suggested to be a useful marker of exposure to sand fly bites and Leishmania infection and a potential tool to monitor the effectiveness of entomological interventions. Exposure to sand fly bites before infection has also been suggested to modulate the severity of the infection. Here, we test these hypotheses by quantifying the anti-saliva IgG response in a cohort study of dogs exposed to natural infection with Leishmania infantum in Brazil. METHODS: IgG responses to crude salivary antigens of the sand fly Lutzomyia longipalpis were measured by ELISA in longitudinal serum samples from 47 previously unexposed sentinel dogs and 11 initially uninfected resident dogs for up to 2 years. Antibody responses were compared to the intensity of transmission, assessed by variation in the incidence of infection between seasons and between dogs. Antibody responses before patent infection were then compared with the severity of infection, assessed using tissue parasite loads and clinical symptoms. RESULTS: Previously unexposed dogs acquired anti-saliva antibody responses within 2 months, and the rate of acquisition increased with the intensity of seasonal transmission. Over the following 2 years, antibody responses varied with seasonal transmission and sand fly numbers, declining rapidly in periods of low transmission. Antibody responses varied greatly between dogs and correlated with the intensity of transmission experienced by individual dogs, measured by the number of days in the field before patent infection. After infection, anti-saliva antibody responses were positively correlated with anti-parasite antibody responses. However, there was no evidence that the degree of exposure to sand fly bites before infection affected the severity of the infection. CONCLUSIONS: Anti-saliva antibody responses are a marker of current transmission intensity in dogs exposed to natural infection with Leishmania infantum, but are not associated with the outcome of infection.
Assuntos
Formação de Anticorpos , Doenças do Cão/patologia , Doenças do Cão/transmissão , Leishmaniose/veterinária , Psychodidae/imunologia , Saliva/imunologia , Animais , Biomarcadores/sangue , Brasil , Progressão da Doença , Doenças do Cão/epidemiologia , Cães , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G/sangue , Incidência , Leishmaniose/epidemiologia , Leishmaniose/patologia , Leishmaniose/transmissão , Estudos Longitudinais , Índice de Gravidade de DoençaRESUMO
BACKGROUND: The relationships between heterogeneities in host infection and infectiousness (transmission to arthropod vectors) can provide important insights for disease management. Here, we quantify heterogeneities in Leishmania infantum parasite numbers in reservoir and non-reservoir host populations, and relate this to their infectiousness during natural infection. Tissue parasite number was evaluated as a potential surrogate marker of host transmission potential. METHODS: Parasite numbers were measured by qPCR in bone marrow and ear skin biopsies of 82 dogs and 34 crab-eating foxes collected during a longitudinal study in Amazon Brazil, for which previous data was available on infectiousness (by xenodiagnosis) and severity of infection. RESULTS: Parasite numbers were highly aggregated both between samples and between individuals. In dogs, total parasite abundance and relative numbers in ear skin compared to bone marrow increased with the duration and severity of infection. Infectiousness to the sandfly vector was associated with high parasite numbers; parasite number in skin was the best predictor of being infectious. Crab-eating foxes, which typically present asymptomatic infection and are non-infectious, had parasite numbers comparable to those of non-infectious dogs. CONCLUSIONS: Skin parasite number provides an indirect marker of infectiousness, and could allow targeted control particularly of highly infectious dogs.
Assuntos
Doenças do Cão/parasitologia , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/veterinária , Carga Parasitária , Pele/parasitologia , Animais , Medula Óssea/parasitologia , Brasil , Portador Sadio/parasitologia , Portador Sadio/veterinária , Cães , Raposas , Leishmaniose Visceral/parasitologia , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND: There is a need for sensitive and specific rapid diagnostic tests (RDT) for canine visceral leishmaniasis. The aims of this study were to evaluate the diagnostic performance of immunochromatographic dipstick RDTs using rK39 antigen for canine visceral leishmaniasis by (i) investigating the sensitivity of RDTs to detect infection, disease and infectiousness in a longitudinal cohort study of natural infection in Brazil, and (ii) using meta-analysis to estimate the sensitivity and specificity of RDTs from published studies. METHODOLOGY: We used a rK39 RDT (Kalazar Detect Canine Rapid Test; Inbios) to test sera collected from 54 sentinel dogs exposed to natural infection in an endemic area of Brazil. Dogs were sampled bimonthly for up to 27 months, and rK39 results compared to those of crude antigen ELISA, PCR, clinical status and infectiousness to sandflies. We then searched MEDLINE and Web of Knowledge (1993-2011) for original studies evaluating the performance of rK39 RDTs in dogs. Meta-analysis of sensitivity and specificity was performed using bivariate mixed effects models. PRINCIPAL FINDINGS: The sensitivity of the rK39 RDT in Brazil to detect infection, disease and infectiousness was 46%, 77% and 78% respectively. Sensitivity increased with time since infection, antibody titre, parasite load, clinical score and infectiousness. Sixteen studies met the inclusion criteria for meta-analysis. The combined sensitivity of rK39 RDTs was 86.7% (95% CI: 76.9-92.8%) to detect clinical disease and 59.3% (37.9-77.6%) to detect infection. Combined specificity was 98.7% (89.5-99.9%). Both sensitivity and specificity varied considerably between studies. CONCLUSION: The diagnostic performance of rK39 RDTs is reasonable for confirmation of infection in suspected clinical cases, but the sensitivity to detect infected dogs is too low for large-scale epidemiological studies and operational control programmes.
Assuntos
Testes Diagnósticos de Rotina/métodos , Doenças do Cão/diagnóstico , Doenças do Cão/parasitologia , Leishmaniose Visceral/veterinária , Parasitologia/métodos , Medicina Veterinária/métodos , Animais , Brasil , Cromatografia de Afinidade , Estudos de Coortes , Cães , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/parasitologia , Estudos Longitudinais , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
Peridomestic transmission of American cutaneous leishmaniasis is increasingly reported and dogs may be a reservoir of Leishmania (Viannia) in this setting. We investigated the prevalence of infection in dogs in Chaparral County, Colombia, the focus of an epidemic of human cutaneous leishmaniasis caused by Leishmania (Viannia) guyanensis. Two (0.72%) of 279 dogs had lesions typical of cutaneous leishmaniasis that were biopsy positive by kinetoplast DNA polymerase chain reaction-Southern blotting. Seroprevalence was 2.2% (6 of 279) by enzyme-linked immunosorbent assay. Buffy coat and ear skin biopsy specimens were positive by polymerase chain reaction-Southern blotting in 7.3% (10 of 137) and 11.4% (12 of 105) of dogs, respectively. Overall 20% of dogs (21 of 105) showed positive results for one or more tests. Amplification and sequencing of the Leishmania 7SL RNA gene identified L. guyanensis in one dog and L. braziliensis in two dogs. No association was identified between the risk factors evaluated and canine infection. Dogs may contribute to transmission but their role in this focus appears to be limited.
Assuntos
Leishmania/isolamento & purificação , Leishmaniose/veterinária , Animais , Sequência de Bases , Colômbia/epidemiologia , Primers do DNA , DNA de Cinetoplasto/genética , Cães , Ensaio de Imunoadsorção Enzimática , Leishmania/genética , Leishmaniose/epidemiologia , Leishmaniose/parasitologia , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Fatores de Risco , Homologia de Sequência do Ácido Nucleico , Estudos SoroepidemiológicosRESUMO
BACKGROUND: Predisposition to heavy or light human hookworm infection is consistently reported in treatment-reinfection studies. A significant role for host genetics in determining hookworm infection intensity has also been shown, but the relationship between host genetics and predisposition has not been investigated. METHODS: A treatment-reinfection study was conducted among 1302 individuals in Brazil. Bivariate variance components analysis was used to estimate heritability for pretreatment and reinfection intensity and to estimate the contribution of genetic and household correlations between phenotypes to the overall phenotypic correlation (ie, predisposition). RESULTS: Heritability for hookworm egg count was 17% before treatment and 25% after reinfection. Predisposition to heavy or light hookworm infection was observed, with a phenotypic correlation of 0.34 between pretreatment and reinfection intensity. This correlation was reduced to 0.23 after including household and environmental covariates. Genetic and household correlations were 0.41 and 1, respectively, and explained 88% of the adjusted phenotypic correlation. CONCLUSIONS: Predisposition to human hookworm infection in this area results from a combination of host genetics and consistent differences in exposure, with the latter explained by household and environmental factors. Unmeasured individual-specific differences in exposure did not contribute to predisposition.
Assuntos
Saúde da Família , Predisposição Genética para Doença , Infecções por Uncinaria/epidemiologia , Infecções por Uncinaria/genética , Adolescente , Adulto , Idoso , Animais , Brasil , Criança , Pré-Escolar , Infecções por Uncinaria/transmissão , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Contagem de Ovos de Parasitas , Fatores de Risco , Adulto JovemRESUMO
Strong statistical associations between soil-transmitted helminths and schistosomes are frequently observed in co-endemic human populations, although the underlying explanations remain poorly understood. This study investigates the contribution of host genetics and domestic environment to hookworm and Schistosoma mansoni infection intensity and evaluates the role of genetic and non-genetic factors in co-variation of infection intensity. Detailed genealogical information allowed assignment of 1303 individuals living in the Brazilian community of Americaninhas, Minas Gerais state, to 25 pedigrees (containing between two and 1159 members) residing in 303 households. The prevalence of co-infection with both hookworms and schistosomes was high (38.5%), with significant correlation between Necator americanus and S. mansoni faecal egg counts. Bivariate variance component analysis demonstrated a modest but significant species-specific heritability for intensity of N. americanus (h(2)=0.196) and S. mansoni infection (h(2)=0.230). However, after accounting for demographic, socio-economic and household risk factors, no evidence for common genetic control of intensity of hookworm and schistosome infection was observed. There was some evidence for residual clustering within households but the majority (63%) of the covariance between N. americanus and S. mansoni infection intensity remained specific to the individual and could not be explained by shared genes, shared environment or other shared demographic, socio-economic or environmental risk factors. Our results emphasize the importance of exposure to hookworm and schistosome infection in driving the association between levels of infection with these species in hosts resident in areas of high transmission and suggest that much of this common exposure occurs outside the home.
Assuntos
Doenças Endêmicas , Infecções por Uncinaria/epidemiologia , Esquistossomose mansoni/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Brasil/epidemiologia , Criança , Pré-Escolar , Comorbidade , Fezes/parasitologia , Feminino , Infecções por Uncinaria/parasitologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Necator americanus/isolamento & purificação , Contagem de Ovos de Parasitas , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/parasitologia , Adulto JovemRESUMO
In response to the increasing need for field trials of experimental DNA vaccines against zoonotic visceral leishmaniasis in dogs, our aim was to validate the use of ELISA protocols which will be suitable for detection of natural infection in vaccinated dogs. We have previously demonstrated that DNA/modified vaccinia virus Ankara (MVA) vaccine expressing tryparedoxin peroxidase (TRYP) induced high titres of TRYP antigen-specific IgG in immunized dogs. Here we report our findings that seroconversion to an unrelated diagnostic antigen rK39 did not occur in vaccinated dogs, and that responses to crude Leishmania infantum promastigote antigen (CLA) were weak and short-lived. This is in contrast to strong responses to both antigens shown in naturally infected dogs. To select an appropriate serological test for measurement of infection incidence, we also tested longitudinal samples from an immunologically well-characterized cohort of naturally infected dogs. The sensitivity of CLA ELISA was superior to that of rK39 in early stage infection (from 2 months before, to 2 months after the first detection of infection by PCR or parasitological culture), and more sensitive than rK39 in cross-sectional sampling (81.0% vs 61.9%). We conclude that CLA ELISA will provide sensitive estimates of L. infantum infection incidence in DNA/MVA vaccinated dogs, though optimal testing would include rK39, or a similar recombinant antigen, to improve overall specificity.
Assuntos
Doenças do Cão/imunologia , Leishmania infantum , Vacinas contra Leishmaniose/imunologia , Leishmaniose Visceral/veterinária , Testes Sorológicos/veterinária , Vacinas de DNA/imunologia , Animais , Anticorpos Antiprotozoários/sangue , Brasil/epidemiologia , Cães , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Grécia/epidemiologia , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/prevenção & controle , Masculino , Sensibilidade e Especificidade , Testes Sorológicos/métodos , Vaccinia virus/genéticaRESUMO
BACKGROUND: Individuals living in areas endemic for helminths are commonly infected with multiple species. Despite increasing emphasis given to the potential health impacts of polyparasitism, few studies have investigated the relative importance of household and environmental factors on the risk of helminth co-infection. Here, we present an investigation of exposure-related risk factors as sources of heterogeneity in the distribution of co-infection with Necator americanus and Schistosoma mansoni in a region of southeastern Brazil. METHODOLOGY: Cross-sectional parasitological and socio-economic data from a community-based household survey were combined with remotely sensed environmental data using a geographical information system. Geo-statistical methods were used to explore patterns of mono- and co-infection with N. americanus and S. mansoni in the region. Bayesian hierarchical models were then developed to identify risk factors for mono- and co-infection in relation to community-based survey data to assess their roles in explaining observed heterogeneity in mono and co-infection with these two helminth species. PRINCIPAL FINDINGS: The majority of individuals had N. americanus (71.1%) and/or S. mansoni (50.3%) infection; 41.0% of individuals were co-infected with both helminths. Prevalence of co-infection with these two species varied substantially across the study area, and there was strong evidence of household clustering. Hierarchical multinomial models demonstrated that relative socio-economic status, household crowding, living in the eastern watershed and high Normalized Difference Vegetation Index (NDVI) were significantly associated with N. americanus and S. mansoni co-infection. These risk factors could, however, only account for an estimated 32% of variability between households. CONCLUSIONS: Our results demonstrate that variability in risk of N. americanus and S. mansoni co-infection between households cannot be entirely explained by exposure-related risk factors, emphasizing the possible role of other household factors in the heterogeneous distribution of helminth co-infection. Untangling the relative contribution of intrinsic host factors from household and environmental determinants therefore remains critical to our understanding of helminth epidemiology.
Assuntos
Helmintíase/epidemiologia , Adolescente , Adulto , Animais , Teorema de Bayes , Brasil/epidemiologia , Criança , Pré-Escolar , Clima , Estudos Transversais , Meio Ambiente , Características da Família , Feminino , Inquéritos Epidemiológicos , Helmintíase/complicações , Helmintos/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , População Rural/estatística & dados numéricos , Fatores Socioeconômicos , Inquéritos e Questionários , População Urbana/estatística & dados numéricosRESUMO
Human schistosomiasis presents the classic, complex disease phenotype, with marked variation in the intensity of infection, the immune response to infection, and the development of schistosome-related pathology. Determining the role of host genetics in schistosomiasis is complicated by the numerous parasite and environmental factors involved in transmission. However, as a result of the increased availability of sequence data, novel statistical methods, and new methods of study design, the last decade has seen significant advances in identifying the role of host genetics in schistosome infection around the world. Many of these advances have taken place in Brazil. Epidemiological studies in Brazil have shown that the intensity of infection (worm burden) is a heritable phenotype (41%). Human genome scans have identified a locus responsible for controlling Schistosoma mansoni infection intensity on chromosome 5q31-q33. There is also evidence for genetic control of pathology due to S. mansoni, with linkage reported to a region containing the gene for the interferon-gamma receptor 1 subunit. Numerous association studies have also provided evidence for major histocompatibility complex control of pathology in schistosomiasis. Recent candidate gene studies suggest a role of other immune response genes in controlling helminth infection and pathology. We chronicle the many advances made in understanding the role of host genetics in S. mansoni infection that have taken place in Brazil by phenotype studied: infection intensity, immune response, and disease development. Results from Brazilian studies are compared with studies of S. mansoni and other schistosome species elsewhere in the world.
Assuntos
Predisposição Genética para Doença/epidemiologia , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/genética , Brasil/epidemiologia , Humanos , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/patologiaRESUMO
Surprisingly few detailed age-stratified data exist on the epidemiology of hookworm and iron status, especially in Latin America. We present data from a cross-sectional survey examining 1332 individuals aged 0-86 years from a community in south-east Brazil for hookworm, anaemia and iron deficiency. Sixty-eight percent of individuals were infected with the human hookworm Necator americanus. The force of infection (lambda=0.354) was similar to estimates from other areas of high hookworm transmission. Individuals from poorer households had significantly higher prevalence and intensity of infection than individuals from better-off households. The prevalence of anaemia, iron deficiency and iron-deficiency anaemia was 11.8%, 12.7% and 4.3%, respectively. Anaemia was most prevalent among young children and the elderly. Univariate analysis showed that haemoglobin and serum ferritin were both significantly negatively associated with hookworm intensity among both school-aged children and adults. Multivariate analysis showed that, after controlling for socio-economic status, iron indicators were significantly associated with heavy hookworm infection. Our results indicate that, even in areas where there is a low overall prevalence of anaemia, hookworm can still have an important impact on host iron status, especially in school-aged children and the elderly.
Assuntos
Anemia Ferropriva/epidemiologia , Necatoríase/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Animais , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Necator americanus , Prevalência , Análise de Regressão , Distribuição por SexoRESUMO
The elimination of seropositive dogs in Brazil has been used to control zoonotic visceral leishmaniasis but with little success. To elucidate the reasons for this, the infectiousness of 50 sentinel dogs exposed to natural Leishmania chagasi infection was assessed through time by xenodiagnosis with the sandfly vector, Lutzomyia longipalpis. Eighteen (43%) of 42 infected dogs became infectious after a median of 333 days in the field (105 days after seroconversion). Seven highly infectious dogs (17%) accounted for >80% of sandfly infections. There were positive correlations between infectiousness and anti-Leishmania immunoglobulin G, parasite detection by polymerase chain reaction, and clinical disease (logistic regression, r2=0.08-0.18). The sensitivity of enzyme-linked immunosorbent assay to detect currently infectious dogs was high (96%) but lower in the latent period (<63%), and specificity was low (24%). Mathematical modeling suggests that culling programs fail because of high incidence of infection and infectiousness, the insensitivity of the diagnostic test to detect infectious dogs, and time delays between diagnosis and culling.