Relatedness and HLA-DRB1 typing may discriminate the magnitude of the genetic susceptibility to tuberculosis using a household contact model.

BACKGROUND: Tuberculosis clusters in families may be due to increased household exposure, shared genetic factors, or both. Household contact studies are useful to control exposure because socioeconomic and environmental conditions are similar to all subjects, allowing the evaluation of the contribution of relatedness to disease development. METHODS: In this study, the familial aggregation of tuberculosis using relatedness and a specific inherited marker (HLA-DRB1) was evaluated. Fifty families, which had at least two cases of tuberculosis diagnosed within the past 5 years, were selected from a cohort of tuberculosis carried out in Recife, Brazil. The first case diagnosed was considered to be a primary case. The secondary attack rate of tuberculosis in household contacts was estimated according to the degree of relatedness. The relative risk of having tuberculosis based on the degree of relatedness household and the population attributable fraction to relatedness were also estimated. HLA-DRB1 typing and attributable etiologic/preventive fractions were calculated among sick and healthy household contacts. RESULTS: Compared to unrelated contacts, the relative risk for tuberculosis adjusted for age was 1.38 (95% CI 0.86 to 2.21). Relatedness contributed 23% to the development of tuberculosis at the population levels. The HLA-DRB1*04 allele group (OR=2.44; p=0.0324; etiologic fraction=0.15) was overrepresented and the DRB1*15 allele group (OR=0.48; p=0.0488; protective fraction=0.19) was underrepresented among household contacts exhibiting tuberculosis. The presence of DRB1 shared alleles between primary cases and their contacts was a risk factor for tuberculosis (p=0.0281). CONCLUSION: This household contact model together with the utilisation of two genetic variables permitted the evaluation of genetic factors contributing towards tuberculosis development.

Ultrastructural characterization of intracellular bacteria of Wuchereria bancrofti.

Ultrastructural observations on the structure and distribution of endosymbiotic bacteria within the tissues of Wuchereria bancrofti are described. In female worms the organisms were observed in the lateral cords of the hypodermis, oocytes, developing eggs and in intrauterine microfilariae. Organisms were also detected in blood microfilariae and in the intestine of third-stage larvae. Bacteria were not observed in male worms.

Cytokine production in acute versus chronic human Schistosomiasis mansoni: the cross-regulatory role of interferon-gamma and interleukin-10 in the responses of peripheral blood mononuclear cells and splenocytes to parasite antigens.

The contribution of interleukin (IL)-10 and interferon (IFN)-gamma to the regulation of type 1 and type 2 cytokine responses was investigated in Brazilians with different clinical forms of schistosomiasis mansoni. Cells from members of a family with acute intestinal schistosomiasis responded to schistosomal soluble egg antigen (SEA) or soluble adult worm antigen preparation (SWAP) with greater amounts of IFN-gamma than did cells from several patients with chronic intestinal schistosomiasis; IL-10 levels were similar. Neutralization of IL-10 had no effect on the SEA-specific IFN-gamma response in patients with acute infection, whereas SWAP-induced IFN-gamma was increased in both groups. Anti-IL-10 also up-regulated SEA-specific IFN-gamma protein and mRNA responses in most splenocyte cultures from hepatosplenic schistosomiasis patients but had no effect on antigen-specific IL-4 or IL-5 production. Neutralization of IFN-gamma resulted in a comparable increase in SWAP-specific IL-10 and IL-5, while IL-4 was not affected. These studies demonstrate that early disease in schistosomiasis is associated with a significant IFN-gamma response and that IL-10 contributes to the suppression of that response during both early and chronic infection.

Effects of non-specific immunopotentiators in experimental Schistosoma mansoni infection. II. Corynebacterium parvum.

The effects of Corynebacterium parvum on host protection, tissue reaction and "in vivo" chemotaxis in Schistosoma mansoni infected mice were studied. The C. parvum was given intraperitoneally using a dose of 0.7 mg, twice a week (for 4 weeks), thirty days before (prophylactic treatment) or after infection (curative treatment). The host protection was evaluated through the recovery of adult worms by liver perfusion and was lower in the prophylactic group as compared to the control group (p = 0.018), resulting in 44% protection. The "in vivo" leukocyte response in both prophylactic and curative groups was higher as compared to the infected/non treated group (p = 0.009 and p = 0.003, respectively). Tissue reactions were described in the experimental and control groups, but there were not remarkable differences among them. The possible biological implications and relevance of the findings for the defensive response of the host and control of schistosomiasis are discussed.

"In vivo" leukocyte chemotaxis in experimental mice Schistosoma mansoni infection.

The "in vivo" chemotaxis was studied in C57Bl/10 mice 10, 30, 50 and 60 days after a Schistosoma mansoni infection in comparison to a control group (uninfected mice). Staphylococcal protein A was injected into a connective tissue air pouch of control and experimental mice and the leukocyte chemotaxis was counted. A decrease in polymorphonuclear (PMN) leukocyte response was found in infected mice in comparison to the control group (p < 0.05). The 10 day infected mice showed a decreased PMN leukocyte response respecting the control group (p < 0.05) and this finding became more evident 30 and 50 days post-infection. Although the PMN leukocyte response of 60 day infected mice increased in comparison to 50 day infected animals, it was still significantly lower the control response. The mononuclear leukocyte response was not significantly different between infected or uninfected mice.

Efeitos de imunopotenciadores nao especificos na infeccao experimental pelo Schistosoma mansoni. I. Levamisole / Effects of non-specific immunopotentiators in experimental Schistosoma mansoni infection. I. Levamisole

Os efeitos do levamisole nas alteracoes histopatologicas, resistencia do hospedeiro e quimiotaxia "in vitro" foram estudados na infeccao experimental pelo Schistosoma mansoni em camundongos da linhagem C57B1/10. O tratamento profilatico resultou em um aumento no numero de vermes adultos obtidos pela perfusao e tambem em uma taxa de mortalidade maior (p<0,05). As alteracoes histopatologicas (figado e intestino) foram similares em todos os grupos. Uma reducao significante da quimiotaxia "in vitro" ocorreu em camundongos controles infectados, assim como naqueles submetidos a tratamento profilatico com levamisole. A atividade quimiotatica atingiu os mesmos niveis dos camundongos controles normais (nao-infectados e nao-tratados com levamisole), quando o esquema curativo foi usado. O levamisole parece aumentar a susceptibilidade de camundongos da linhagem C57B1/10 a infeccao pelo S. mansoni quando administrado antes da infeccao e normaliza a atividade quimiotatica, quando dado apos a infeccao.

[Effects of non-specific immunopotentiators on experimental Schistosoma mansoni infection. I. Levamisole]. / Efeitos de imunopotenciadores não específicos na infecção experimental pelo Schistosoma mansoni. I. Levamisole.

The effects of levamisole on the histopathological changes, host's resistance and "in vivo" chemotaxis in Schistosoma mansoni experimental infection of C57Bl/10 inbred mice were studied. Prophylactic treatment resulted in an increase in the number of adult worms obtained by perfusion and also increased the mortality rate (p < 0.05). The histopathological changes (liver and intestines) were similar in all the groups. A significant reduction of "in vivo" chemotaxis occurred in infected control mice as well as in those submitted to prophylactic treatment with levamisole. Chemotactic activity reached the same levels of normal control mice (non-infected and non-treated with levamisole), when the curative scheme was used. Levamisole seems to increase the susceptibility of inbred C57Bl/10 mice to the infection with S. mansoni when administered prior to the infection and increase the chemotactic activity to normal levels when given after infection.