BackgroundIn some tropical countries, such as Brazil, schistosomiasis control programs have led to a significant reduction in the prevalence and parasite burden of endemic populations. In this setting, the Kato-Katz technique, as the standard diagnostic method for the diagnosis of Schistosoma mansoni infections, which involves the analysis of two slides from one fecal sample, loses its sensitivity. As a result, a significant number of infected individuals are not detected. The objective of this study was to perform extensive parasitological testing of up to three fecal samples and include a rapid urine test (POC-CCA) in a moderate prevalence area in Northern Minas Gerais, Brazil, and evaluate the performance of each test separately and in combination.Methods and findingsA total of 254 individuals were examined with variants of the standard Kato-Katz technique (up to18 Kato-Katz slides prepared from three fecal samples), a modified Helmintex (30 g of feces), the saline gradient (500 mg of feces), and the POC-CCA methods. We established a reference standard taking into consideration all the positive results in any of the parasitological exams. Evaluation of the parasite burden by two Kato-Katz slides confirmed that most of the individuals harbored a light infection. When additional slides and different parasitological methods were included, the estimated prevalence rose 2.3 times, from 20.4% to 45.9%. The best sensitivity was obtained with the Helmintex method (84%). All parasitological methods readily detected a high or moderate intensity of infection; however, all lost their high sensitivity in the case of low or very low intensity infections. The overall sensitivity of POC-CCA (64.9%) was similar to the six Kato-Katz slides from three fecal samples. However, POC-CCA showed low concordance (κ = 0.34) when compared with the reference standard.ConclusionsThe recommended Kato-Katz method largely underestimated the prevalence of S. mansoni infection. Because the best performance was achieved with a modified Helmintex method, this technique might serve as a more precise reference standard. An extended number of Kato-Katz slides in combination with other parasitological methods or with POC-CCA was able to detect more than 80% of egg-positive individuals; however, the rapid urine test (POC-CCA) produced a considerable percentage of false positive results.

Ancylostoma ceylanicum Aw and ES mediators have an important therapeutic potential in experimental colitis in mice, which may provide a more socially acceptable form of therapy for patients with IBDs as opposed to using living worms. Our results support the urgency of further isolation and recombinant expression of active hookworm products responsible for the beneficial effects on colitis.

Infection by nematode parasites with a pulmonary migration in their life cycle and allergic asthma are two highly prevalent diseases in humans; therefore, one may expect both may occur concomitantly. There is a predominant and essential role of Th2 lymphocytes in the mechanisms underlying the control of parasite elimination as well as in the pathology observed in the asthmatic lung. The consequences of such situations have been explored, with controversial results, justifying the development of experimental models in which the relationship between allergic airway inflammation and helminth infection might be evaluated. The present work describes the inflammatory, humoral, and functional changes that occur in the lung of rats after single (subcutaneous inoculation of 1,500 L3 larvae) or multiple (five weekly subcutaneous inoculations of 1,500 L3 larvae) Strongyloides venezuelensis infections. The results show that the migration of S. venezuelensis larvae through the lungs of infected rats induces a local eosinophilic inflammation process which is mostly focal and parenchymal for rats infected a single time and which is peribronchial after multiple infections. The inflammatory process is accompanied by mucus hypersecretion, thickening of bronchial epithelial and muscle layers, and local increase in immunoglobulin E concentrations that peak after 5 to 7 days and are resolved after 12 days of single or multiple infections. The peak of lung immunopathologic changes observed in infected rats coincides with lung airway hyperresponsiveness (AHR), a key functional alteration in asthma. We propose that this experimental model is ideal to carry out further studies on immunoprotection against nematode infection versus immunopathology of allergic airway inflammation.

A cross-sectional study was conducted on a randomised sample of 405 children aged 6-71 months in Brazil to investigate the association between nutritional status, environmental and socio-economic factors and Giardialamblia infection. Data collection entailed an interview, anthropometric measurements and the collection of faeces and venous blood samples. The analysis was performed using multivariate logistic regression. The prevalence rate for G. lamblia was 26.3%. Nutritional status evaluation showed that 7.9% of the children had chronic malnutrition and 11.1% had acute malnutrition. The risk factors associated with infection by G. lamblia were an age of 2 years or older [odds ratio (OR)=2.4], living in a two-bedroom house or smaller (OR=2.3), living among a family of five or more people (OR=2.4) and living in a house without access to a sewerage system (OR=2.1). Non-participation in the social service programme was associated with a lower risk of infection (OR=0.2). The model adjusted for age, including only biochemical and nutritional variables, showed weak associations with G. lamblia infection for two variables: inadequate animal protein intake according to the Dietary Reference Intake recommendation and low haemoglobin concentration. The sociodemographic and environmental risk factors classically described were associated with G. lamblia infection, but nutritional variables were only weakly associated with it.

BackgroundOne of the most important drawbacks in visceral leishmaniasis (VL) population studies is the difficulty of diagnosing asymptomatic carriers. The aim of this study, conducted in an urban area in the Southeast of Brazil, was to evaluate the performance of serology to identify asymptomatic VL infection in participants selected from a cohort with a two-year follow-up period.MethodologyBlood samples were collected in 2001 from 136 cohort participants (97 positive and 39 negatives, PCR/hybridization carried out in 1999). They were clinically evaluated and none had progressed to disease from their asymptomatic state. As controls, blood samples from 22 control individuals and 8 patients with kala-azar were collected. Two molecular biology techniques (reference tests) were performed: PCR with Leishmania-generic primer followed by hybridization using L. infantum probe, and PCR with specific primer to L. donovani complex. Plasma samples were tested by ELISA using three different antigens: L. infantum and L. amazonensis crude antigens, and rK39 recombinant protein. Accuracy of the serological tests was evaluated using sensitivity, specificity, likelihood ratio and ROC curve.FindingsThe presence of Leishmania was confirmed, by molecular techniques, in all kala-azar patients and in 117 (86%) of the 136 cohort participants. Kala-azar patients showed high reactivity in ELISAs, whereas asymptomatic individuals presented low reactivity against the antigens tested. When compared to molecular techniques, the L. amazonensis and L. infantum antigens showed higher sensitivity (49.6% and 41.0%, respectively) than rK39 (26.5%); however, the specificity of rK39 was higher (73.7%) than L. amazonensis (52.6%) and L. infantum antigens (36.8%). Moreover, there was low agreement among the different antigens used (kappa<0.10).ConclusionsSerological tests were inaccurate for diagnosing asymptomatic infections compared to molecular methods; this could lead to misclassification bias in population studies. Therefore, studies which have used serological assays to estimate prevalence, to evaluate intervention programs or to identify risk factors for Leishmania infection, may have had their results compromised.

In human schistosomiasis, the concentrations of the chemokine macrophage inflammatory protein 1␣ (MIP-1␣/CCL3) is greater in the plasma of patients with clinical hepatosplenic disease. The objective of the present study was to confirm the ability of CCL3 to detect severe disease in patients classified by ultrasonography (US) and to evaluate the potential role of CCL3 in Schistosoma mansoni-infected mice. CCL3 was measured by enzyme-linked immunosorbent assay in the plasma of S. mansoni-infected patients. CCL3-deficient mice were infected with 25 cercariae, and various inflammatory and infectious indices were evaluated. The concentration of CCL3 was higher in the plasma of S. mansoni-infected than noninfected patients. Moreover, CCL3 was greater in those with US-defined hepatosplenic than with the intestinal form of the disease. In CCL3-deficient mice, the size of the granuloma and the liver eosinophil peroxidase activity and collagen content were diminished compared to wild-type mice. In CCL3-deficient mice, the worm burden after 14 weeks of infection, but not after 9 weeks, was consistently smaller. The in vitro response of mesenteric lymph node cells to antigen stimulation was characterized by lower levels of interleukin-4 (IL-4) and IL-10. CCL3 is a marker of disease severity in infected humans, and experimental studies in mice suggest that CCL3 may be a causative factor in the development of severe schistosomiasis.Schistosomiasis is one of the most prevalent helminth diseases in the world and is caused by blood flukes of the Schistosoma genus (36). In infected individuals, the granulomatous inflammation in response to egg deposition in the liver in the case of Schistosoma mansoni is the major pathological finding and accounts for most of the clinical symptoms. Worm oviposition at 5 to 6 weeks poses a strong Th2 bias in the immune response against infection (6) while also inhibiting the Th1 component (12,42). Nonetheless, the granulomatous response that is maximal during the first few weeks after initial oviposition is also subjected to immunomodulation. Apart from interleukin-10 (IL-10) (29), other factors may also be involved in this process. For example, recent literature suggests that, in animal models, the granulomatous response that occurs at chronic time points is dependent on the soluble form of the IL-13 receptor ␣2 (27). In patients, failure in modulating the response might lead to the development severe schistosomiasis later in life (15). Indeed, a direct consequence of the persistence of an exacerbated immune response appears to be the development of large granulomatous reactions associated with intense collagen deposition (20) and the development of hepatosplenic schistosomiasis. Therefore, there is much scientific interest in the understanding of the mechanisms and inflammatory mediators underlying egg-induced granulomatous response, with the ultimate goal of proposing strategies to modulate fibrosis. It is known, however, that prevention of granuloma formation may be dangerous, since lethality ...

SUMMARYThis review discusses experimental evidences that indicate the IgE participation on the effector mechanisms that leads to gastrointestinal nematode elimination. Data discussed here showed that, for most experimental models, the immune response involved in nematode elimination is regulated by Th-2 type cytokines (especially IL-4). However, the mechanism(s) that result in worm elimination is not clear and might be distinct in different nematode species. Parasite specific IgE production, especially the IgE produced by the intestinal mucosae or associated lymphoid organs could participate in the intestinal elimination of Trichinella spiralis from infected rats. Intestinal IgE may also be important to the protective mechanism developed against other gastrointestinal nematodes that penetrate the murine duodenum mucosa tissue, such as Strongyloides venezuelensis and Heligmosomoides polygyrus. At least in Trichinella spiralis infected rats, the results indicated that intestinal IgE might work independently from mast cell degranulation for worm elimination.

The present study was carried out to investigate the immune response against Strongyloides venezuelensis infection in Balb/c mice previously immunized with larva-antigens or primed with live-larvae. Our results indicate that all primed mice developed a strong protection against challenge infection that remained active for 45 days. In mice primed with live-larvae the challenge infection resulted in great reduction of migrating larvae and the worms were completely eliminated from the small intestine before maturation. The protection pattern did not alter when the primary infection was aborted by drug treatment. In these experimental groups, the challenge infection was accompanied by a type-2 predominant immune response, intense IgE and reactive IgG1 production, and granulocyte infiltration in skin, lungs and intestine. The challenge infection in antigen-immunized mice also resulted in great reduction of migrating larvae. However, the worms that reached the host intestine matured, produced eggs and were eliminated similarly to the ones from nonimmunized mice. Protective mechanisms after immunization with larva antigen were migrating larva-specific and associated with a strong and mixed Th1 and Th2 response, without tissue granulocyte infiltration. In conclusion, protective immunity induced by a previous infection or antigen-immunization are stage-specific and operate through different effector mechanisms.