Influence of Polymorphism (-G308A) TNF-α on the Periportal Fibrosis Regression of Schistosomiasis After Specific Treatment.

AIMS: Tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine and important mediator of severity for periportal fibrosis (PPF). We hypothesized that the (-G380A) polymorphism in the TNF-α gene is associated with regression of PPF after treatment for schistosomiasis mansoni. METHODS: This is a retrospective cohort study, involving 124 Brazilian patients infected with Schistosoma mansoni, who were followed for 2 years after treatment to estimate the likelihood of PPF regression. Sociodemographic and clinical factors were also identified, with emphasis on specific treatment. RESULTS: No statistical difference was observed between sociodemographic and clinical factors among the exposed groups. Genotypes (-308) GA/AA were positively associated with the degree of PFF regression (relative risk [RR] = 0.52; ρ = 0.025), as well as in the image pattern of PPF (RR = 0.56; ρ = 0.048), when compared with the genotype (-308) GG. There was no statistical difference in TNF-α serum levels between the exposed groups. CONCLUSIONS: These results suggest that the (-G308A) polymorphism of the TNF-α gene may be one of the factors that prevents the regression of the degree and pattern of PPF in the Brazilian population, and thus it may potentially be a predictive factor of PPF intensity in schistosomiasis.

Correlation between platelet count and both liver fibrosis and spleen diameter in patients with schistosomiasis mansoni.

CONTEXT: Studies have described the correlation between platelet count and the stages of fibrosis in chronic viral hepatitis, but few publications have studied this correlation in Schistosomiasis mansoni. OBJECTIVES: Therefore, this study aimed to correlate platelet count with both the periportal fibrosis pattern and spleen diameter evaluated by ultrasound exam in patients with Schistosomiasis mansoni. METHODS: Patients with Schistosomiasis mansoni were evaluated by abdominal ultrasound by a single examiner for the determination of periportal fibrosis pattern (Niamey classification) and spleen diameter. Platelet counts were performed in an automated cell counter. RESULTS: One hundred eighty-seven patients with Schistosomiasis mansoni (mean age: 50.2 years) were included in the study, 114 of whom (61%) were women. Based on the Niamey classification, the ultrasound analysis revealed that 37, 64, 64 and 22 patients exhibited patterns C, D, E and F, respectively. In these four groups, the mean number of platelets was 264, 196, 127 and 103 x 109/L and mean spleen diameter was 9.2, 11.9, 14.9 and 16.2 centimeters, respectively. A reduction in platelet count was significantly associated with both the progression of the periportal fibrosis and the increase in spleen size. CONCLUSIONS: Platelet count in patients with Schistosomiasis mansoni was inversely correlated with the severity of periportal fibrosis and spleen diameter.

Correlation beteeen platelet count and both livr fibrosis and spleen diameter in patients with schistosomiasis mansnni / Correlação entre o número de plaquetas e o grau de fibrose hepática e o tamanho do baço em pacientes com Esquistossomose mansoni

Context Studies have described the correlation between platelet count and the stages of fibrosis in chronic viral hepatitis, but few publications have studied this correlation in Schistosomiasis mansoni. Objectives Therefore, this study aimed to correlate platelet count with both the periportal fibrosis pattern and spleen diameter evaluated by ultrasound exam in patients with Schistosomiasis mansoni. Methods Patients with Schistosomiasis mansoni were evaluated by abdominal ultrasound by a single examiner for the determination of periportal fibrosis pattern (Niamey classification) and spleen diameter. Platelet counts were performed in an automated cell counter. Results One hundred eighty-seven patients with Schistosomiasis mansoni (mean age: 50.2 years) were included in the study, 114 of whom (61%) were women. Based on the Niamey classification, the ultrasound analysis revealed that 37, 64, 64 and 22 patients exhibited patterns C, D, E and F, respectively. In these four groups, the mean number of platelets was 264, 196, 127 and 103 x 109/L and mean spleen diameter was 9.2, 11.9, 14.9 and 16.2 centimeters, respectively. A reduction in platelet count was significantly associated with both the progression of the periportal fibrosis and the increase in spleen size. Conclusions Platelet count in patients with Schistosomiasis mansoni was inversely correlated with the severity of periportal fibrosis and spleen diameter. .

Contexto Estudos vem descrevendo correlação entre o número de plaquetas e o grau de fibrose hepática na hepatite viral crônica, mas poucas publicações estudaram esta correlação em pacientes com Esquistossomose mansoni. Objetivos Correlacionar a contagem de plaquetas com o padrão de fibrose periportal e com o diâmetro do baço, avaliados pela ultrassonografia em pacientes com Esquistossomose mansoni. Métodos Os pacientes com Esquistossomose mansoni foram avaliados pela ultrassonografia abdominal, por um único examinador, para determinação do padrão de fibrose periportal (classificação de Niamey) e do diâmetro do baço. A contagem de plaquetas foi realizada em contador automatizado. Resultados Cento e oitenta e sete pacientes com Esquistossomose mansoni com média de idade de 50,2 anos foram incluídos no estudo, 114 (61%) dos quais eram mulheres. De acordo com a classificação de Niamey, a ultrassonografia revelou que 37, 64, 64 e 22 pacientes exibiam padrões C, D, E e F, respectivamente. Nestes quatro grupos, o número médio de plaquetas foi 264, 196, 127 e 103 x 109/L, respectivamente, e o diâmetro médio do baço foi 9,2, 11,9, 14,9 e 16,2 centímetros, respectivamente. Observou-se, portanto, redução significativa na contagem de plaquetas associada à progressão da fibrose periportal e ao aumento do tamanho do baço. Conclusões Neste estudo verificou-se que a contagem de plaquetas foi inversamente correlacionada com o padrão de fibrose periportal, como também com o diâmetro do baço nos pacientes com Esquistossomose mansoni. .

HBV and HCV serological markers in patients with the hepatosplenic form of mansonic schistosomiasis.

CONTEXT: Blood transfusion is one of the major risk factors for the transmission of the hepatitis B (HBV) and C (HCV) viruses. However, there are no reports describing the endoscopic transmission of these viruses in patients with the hepatosplenic form of schistosomiasis. OBJECTIVE: To estimate the prevalence of serological markers of HBV and HCV in patients with the hepatosplenic form of schistosomiasis and evaluate the possible risk factors associated with these infections. METHODS: A cross-sectional study was conducted on 230 patients with hepatosplenic form of schistosomiasis who attended a university hospital in Recife, Northeastern Brazil, from February to August 2008. The patients answered a standardized questionnaire about risk factors. Serum samples were analyzed for anti-HBc total, anti-HBs, HBsAg, and anti-HCV using enzyme-linked immunosorbent assays. Univariate analysis and multiple logistic regression were performed. RESULTS: The prevalence was 30% for anti-HBc total and/or HBsAg and 7.4% for anti-HCV. There was a higher frequency of the serological markers in females and in patients aged .50 years. A significant association was detected between the presence of anti-HCV and the receipt of six or more blood transfusions. There was no association of history and number of digestive endoscopies with the serological markers analyzed. CONCLUSIONS: We observed a higher prevalence of serological markers for HBV and a lower prevalence of anti-HCV. Our results indicate that females and patients of an advanced age are the most affected categories and that patients that received multiple transfusions are at a higher probability of HCV infection.

HBV and HCV serological markers in patients with the hepatosplenic form of mansonic schistosomiasis / Marcadores sorológicos do VHB e VHC em pacientes com esquistossomose mansônica na forma hepatoesplênica

CONTEXT: Blood transfusion is one of the major risk factors for the transmission of the hepatitis B (HBV) and C (HCV) viruses. However, there are no reports describing the endoscopic transmission of these viruses in patients with the hepatosplenic form of schistosomiasis. OBJECTIVE: To estimate the prevalence of serological markers of HBV and HCV in patients with the hepatosplenic form of schistosomiasis and evaluate the possible risk factors associated with these infections. METHODS: A cross-sectional study was conducted on 230 patients with hepatosplenic form of schistosomiasis who attended a university hospital in Recife, Northeastern Brazil, from February to August 2008. The patients answered a standardized questionnaire about risk factors. Serum samples were analyzed for anti-HBc total, anti-HBs, HBsAg, and anti-HCV using enzyme-linked immunosorbent assays. Univariate analysis and multiple logistic regression were performed. RESULTS: The prevalence was 30 percent for anti-HBc total and/or HBsAg and 7.4 percent for anti-HCV. There was a higher frequency of the serological markers in females and in patients aged .50 years. A significant association was detected between the presence of anti-HCV and the receipt of six or more blood transfusions. There was no association of history and number of digestive endoscopies with the serological markers analyzed. CONCLUSIONS: We observed a higher prevalence of serological markers for HBV and a lower prevalence of anti-HCV. Our results indicate that females and patients of an advanced age are the most affected categories and that patients that received multiple transfusions are at a higher probability of HCV infection.

CONTEXTO: A transfusão sanguínea destaca-se entre os fatores de risco implicados na transmissão dos vírus das hepatites B (VHB) e C (VHC); entretanto não há relatos da transmissão endoscópica destes vírus em pacientes com esquistossomose na forma hepatoesplênica. OBJETIVO: Estimar a prevalência dos marcadores sorológicos do VHB e VHC em pacientes com esquistossomose hepatoesplênica e avaliar os possíveis fatores de risco associados a essas infecções. MÉTODOS: Estudo do tipo transversal, com 230 pacientes com esquistossomose hepatoesplênica atendidos em um Hospital Universitário de Recife, PE, Brasil, no período de fevereiro a agosto de 2008. Os pacientes responderam a um questionário padronizado sobre os fatores de risco. Nas amostras de soro foram pesquisados o anti-HBc total, o anti-HBs, o HBsAg e o anti-VHC por ensaio imunoenzimático. As análises estatísticas utilizadas foram a univariada e a regressão logística múltipla. RESULTADOS: Encontrou-se prevalencia de 30 por cento para anti-HBc total e/ou HBsAg e 7,4 por cento para o anti-VHC. Houve maior frequencia de pacientes positivos do sexo feminino e idade .50 anos para os marcadores analisados. Verificou-se associação significativa entre a presenca do anti-HCV e a categoria de seis ou mais transfusões. Nao foi constatada associação do antecedente e numero de endoscopias digestivas com os marcadores sorologicos analisados. CONCLUSÕES: Constatou-se maior prevalência de marcadores sorológicos do VHB e menor prevalência para o anti-VHC. Evidenciou-se o sexo feminino e paciente de idade avançada como as categorias mais atingidas e maior probabilidade da infecção pelo VHC em pacientes politransfundidos.

Spatial distribution of Schistosoma mansoni infection before and after chemotherapy with two praziquantel doses in a community of Pernambuco, Brazil.

Praziquantel chemotherapy has been the focus of the Schistosomiasis Control Program in Brazil for the past two decades. Nevertheless, information on the impact of selective chemotherapy against Schistosoma mansoni infection under the conditions confronted by the health teams in endemic municipalities remains scarce. This paper compares the spatial pattern of infection before and after treatment with either a 40 mg/kg or 60 mg/kg dose of praziquantel by determining the intensity of spatial cluster among patients at 180 and 360 days after treatment. The spatial-temporal distribution of egg-positive patients was analysed in a Geographic Information System using the kernel smoothing technique. While all patients became egg-negative after 21 days, 17.9% and 30.9% reverted to an egg-positive condition after 180 and 360 days, respectively. Both the prevalence and intensity of infection after treatment were significantly lower in the 60 mg/kg than in the 40 mg/kg treatment group. The higher intensity of the kernel in the 40 mg/kg group compared to the 60 mg/kg group, at both 180 and 360 days, reflects the higher number of reverted cases in the lower dose group. Auxiliary, preventive measures to control transmission should be integrated with chemotherapy to achieve a more enduring impact.

Spatial distribution of Schistosoma mansoni infection before and after chemotherapy with two praziquantel doses in a community of Pernambuco, Brazil

Praziquantel chemotherapy has been the focus of the Schistosomiasis Control Program in Brazil for the past two decades. Nevertheless, information on the impact of selective chemotherapy against Schistosoma mansoni infection under the conditions confronted by the health teams in endemic municipalities remains scarce. This paper compares the spatial pattern of infection before and after treatment with either a 40 mg/kg or 60 mg/kg dose of praziquantel by determining the intensity of spatial cluster among patients at 180 and 360 days after treatment. The spatial-temporal distribution of egg-positive patients was analysed in a Geographic Information System using the kernel smoothing technique. While all patients became egg-negative after 21 days, 17.9 percent and 30.9 percent reverted to an egg-positive condition after 180 and 360 days, respectively. Both the prevalence and intensity of infection after treatment were significantly lower in the 60 mg/kg than in the 40 mg/kg treatment group. The higher intensity of the kernel in the 40 mg/kg group compared to the 60 mg/kg group, at both 180 and 360 days, reflects the higher number of reverted cases in the lower dose group. Auxiliary, preventive measures to control transmission should be integrated with chemotherapy to achieve a more enduring impact.

[Serum globulin levels and intensity of hepatic fibrosis in patients with mansonic schistosomiasis]. / Níveis séricos de globulinas e a intensidade da fibrose hepática em pacientes com esquistossomose mansônica.

BACKGROUND: A correlation between the levels of serum globulins and the hepatic fibrosis degree in chronic hepatitis was described, but reports in schistosomiasis mansoni have not been found. OBJECTIVE: To evaluate the serum globulins and IgG levels, and periportal fibrosis intensity measured by ultrasound in patients with schistosomiasis mansoni. METHODS: Between November, 2006 and February 2007, 41 patients which were eligible, filled them a questionnaire and had their levels of serum IgG measured by immunoturbidimetry and globulins indirectly measured by the Biuret method. The ultrasound was carried out by a single researcher, according to the Cairo and Niamey protocols. RESULTS: The average age was 41 years old and 25 female patients (61%). Ten patients (24%) from 41 showed serum globulins levels raised and 21 (51%) presented elevated IgG levels. According to the Cairo classification, 21 patients showed grade I of fibrosis, 18 grade II and 2 grade III; and by the Niamey classification 8 showed standard C, 20 D, and 13 E. Those with grade II or III of fibrosis had higher IgG levels than the ones with grade I (P = 0.047), as well as those who showed standards D and E as compared to C (P = 0.011). There was no association between the globulins levels and the intensity of fibrosis. CONCLUSION: In patients with schistosomiasis mansoni, an increase of the IgG serum levels was observed according to the progression from periportal fibrosis intensity, but the same was not founded with globulins levels.

Níveis séricos de globulinas e a intensidade da fibrose hepática em pacientes com esquistossomose mansônica / Serum globulin levels and intensity of hepatic fibrosis in patients with mansonic schistosomiasis

CONTEXTO: Tem sido descrita correlação entre os níveis séricos de globulinas e o grau de fibrose hepática nas hepatites crônicas, mas não se encontram relatos na esquistossomose mansônica. OBJETIVO: Avaliar os níveis séricos de globulinas e de IgG, e a intensidade da fibrose periportal mensurada pela ultrassonografia em pacientes com esquistossomose mansônica. MÉTODOS: Entre novembro de 2006 e fevereiro de 2007, foram estudados 41 pacientes que preencheram ficha clínica e realizaram dosagens de IgG por imunoturbidimetria e de globulinas indiretamente pelo método do biureto. A ultrassonografia foi realizada por um único pesquisador, seguindo os protocolos do Cairo e de Niamey. RESULTADOS: A média de idade foi 41 anos, sendo 25 pacientes (61 por cento) do sexo feminino. Dez dos 41 pacientes (24 por cento) apresentaram elevação dos níveis séricos de globulinas e 21 (51 por cento) dos de IgG. Conforme a classificação do Cairo, 21 pacientes apresentaram grau I de fibrose, 18 grau II e 2 grau III, e pela classificação de Niamey 8 apresentavam padrão C, 20 D e 13 E. Aqueles com graus II ou III de fibrose tiveram maiores níveis de IgG do que os de grau I (P = 0,047), assim como aqueles que apresentaram padrões D e E em relação ao C (P = 0,011). Não houve associação entre os níveis de globulinas e o grau ou padrão de fibrose. CONCLUSÃO: Em pacientes com esquistossomose mansônica, observou-se elevação dos níveis séricos de IgG de acordo com a progressão do grau e do padrão de fibrose periportal, mas o mesmo não se observou com os níveis de globulinas.

BACKGROUND: A correlation between the levels of serum globulins and the hepatic fibrosis degree in chronic hepatitis was described, but reports in schistosomiasis mansoni have not been found. OBJECTIVE: To evaluate the serum globulins and IgG levels, and periportal fibrosis intensity measured by ultrasound in patients with schistosomiasis mansoni. METHODS: Between November, 2006 and February 2007, 41 patients which were eligible, filled them a questionnaire and had their levels of serum IgG measured by immunoturbidimetry and globulins indirectly measured by the Biuret method. The ultrasound was carried out by a single researcher, according to the Cairo and Niamey protocols. RESULTS: The average age was 41 years old and 25 female patients (61 percent). Ten patients (24 percent) from 41 showed serum globulins levels raised and 21 (51 percent) presented elevated IgG levels. According to the Cairo classification, 21 patients showed grade I of fibrosis, 18 grade II and 2 grade III; and by the Niamey classification 8 showed standard C, 20 D, and 13 E. Those with grade II or III of fibrosis had higher IgG levels than the ones with grade I (P = 0,047), as well as those who showed standards D and E as compared to C (P = 0,011). There was no association between the globulins levels and the intensity of fibrosis. CONCLUSION: In patients with schistosomiasis mansoni, an increase of the IgG serum levels was observed according to the progression from periportal fibrosis intensity, but the same was not founded with globulins levels.

Treatment of human acute schistosomiasis with oxamniquine induces an increase in interferon-gamma response to Schistosoma mansoni antigens.

Patients with acute schistosomiasis were studied before and after oxamniquine treatment. They had been exposed to cercariae 5 to 9 weeks before, and presented compatible clinical manifestations, eosinophilia, and high levels of total IgE. Interferon-gamma (IFN-gamma) and interleukin-4 were measured by ELISA in whole blood samples under soluble egg antigen or soluble adult worm preparation stimulation. After treatment, the reduction of leukocytosis and eosinophilia were not significant, but total IgE levels decreased significantly, in contrast to IFN-gamma levels that were significantly increased. The oxamniquine treatment of acute schistosomiasis patients is followed by an improvement of a Th1 response in vitro. If this response has a protective aspect is unknown, and some investigations need to be realized.

Evaluation of splenomegaly in the hepatosplenic form of mansonic schistosomiasis.

This study was aimed to evaluate splenomegaly in patients with the hepatosplenic (HS) form of mansonic schistosomiasis (MS), analyzing the size and weight of the spleen and their relationships with patients' gender and age. Between October, 1993 to July, 1998, 78 patients with the HS form of MS had undergone splenectomy as treatment of choice for bleeding due to portal hypertension, at Hospital das Clínicas, Pernambuco, Brazil. By means of abdominal palpation, the excess spleen felt below the left costal edge was measured, and the weight was obtained after splenectomy along with the histopathological analysis. Liver biopsy was performed intraoperatively in order to confirm MS and to rule out other liver diseases. The mean age of the 78 patients were 45 years and 41 of them (53%) were female. The average spleen weight was 912g and the mean spleen size palpable below the left costal edge was 9.1cm. There was a positive relationship between size and weight (p<0.001). Spleen weight and size were larger in males (p=0.007 and p=0.001, respectively). An inverse correlation between age and spleen weight was observed (p<0.001). A classification based upon spleen weight showed 53% of patients presenting a moderate (501-1000g) and 33% a severe (>1001g) splenomegaly. As for the spleen size, the classification showed 64% of patients presenting moderate (4.1-10cm below the left costal edge) and 21% severe (>10cm) splenomegaly. In conclusion, splenomegaly may be considered a key physical finding in patients with HS form of MS, and we found a good correlation between the spleen sizes clinically evaluated with its weight. The majority of cases presents a moderate to severe splenomegaly and spleen size is larger in men and it seems to decrease with aging.

Treatment of human acute schistosomiasis with oxamniquine induces an increase in interferon-gamma response to Schistosoma mansoni antigens

Patients with acute schistosomiasis were studied before and after oxamniquine treatment. They had been exposed to cercariae 5 to 9 weeks before, and presented compatible clinical manifestations, eosinophilia, and high levels of total IgE. Interferon-gamma (IFN-gamma) and interleukin-4 were measured by ELISA in whole blood samples under soluble egg antigen or soluble adult worm preparation stimulation. After treatment, the reduction of leukocytosis and eosinophilia were not significant, but total IgE levels decreased significantly, in contrast to IFN-gamma levels that were significantly increased. The oxamniquine treatment of acute schistosomiasis patients is followed by an improvement of a Th1 response in vitro. If this response has a protective aspect is unknown, and some investigations need to be realized.

Preliminar evaluation of cytokines in the hepatitis C-schistosomiasis co-infection

Evaluation of hepatic fibrosis is usually performed by histopathological examination of biopsies. However, this is an invasive and potentially dangerous procedure. Several studies have proposed serum biological markers of hepatic fibrosis. This communication evaluates the use of serum cytokines as markers of hepatic fibrosis in hepatitis C, schistosomiasis, and co-infection.

Preliminar evaluation of cytokines in the hepatitis C-schistosomiasis co-infection.

Evaluation of hepatic fibrosis is usually performed by histopathological examination of biopsies. However, this is an invasive and potentially dangerous procedure. Several studies have proposed serum biological markers of hepatic fibrosis. This communication evaluates the use of serum cytokines as markers of hepatic fibrosis in hepatitis C, schistosomiasis, and co-infection.

Hypertensive portal colopathy in schistosomiasis mansoni--proposal for a classification.

Portal hypertension is a frequent complication of chronic liver disease, detected not only in schistosomiasis, but also in cirrhosis of any etiology. Vascular alterations in the colonic mucosa are a potential source for acute or chronic bleeding and have been observed in patients with portal hypertension. The purpose of this prospective study was to describe and propose a classification for the vascular alterations of portal hypertension in the colonic mucosa among patients with hepatosplenic schistosomiasis mansoni. One or more alterations of portal colopathy were observed in all patients and they were classified according to their intensity, obeying the classification proposed by the authors. Portal colopathy is an important finding in hepatosplenic schistosomiasis and might be the cause of lower gastrointestinal bleeding in patients with severe portal hypertension.

Evaluation of tests based on the antibody response to keyhole limpet haemocyanin and soluble egg antigen to differentiate acute and chronic human schistosomiasis mansoni.

Specific IgG and IgM responses to soluble egg antigen (SEA) and keyhole limpet haemocyanin (KLH) were measured by ELISA in patients with acute and chronic schistosomiasis. The tests based upon IgM and IgG antibodies responses to KLH presented the best diagnostic discrimination, and can be used in conjunction with clinical and epidemiological data to the differential diagnosis of acute schistosomiasis.

Hypertensive portal colopathy in schistosomiasis mansoni: proposal for a classification

Portal hypertension is a frequent complication of chronic liver disease, detected not only in schistosomiasis, but also in cirrhosis of any etiology. Vascular alterations in the colonic mucosa are a potential source for acute or chronic bleeding and have been observed in patients with portal hypertension. The purpose of this prospective study was to describe and propose a classification for the vascular alterations of portal hypertension in the colonic mucosa among patients with hepatosplenic schistosomiasis mansoni. One or more alterations of portal colopathy were observed in all patients and they were classified according to their intensity, obeying the classification proposed by the authors. Portal colopathy is an important finding in hepatosplenic schistosomiasis and might be the cause of lower gastrointestinal bleeding in patients with severe portal hypertension.

Evaluation of tests based on the antibody response to keyhole limpet haemocyanin and soluble egg antigen to differentiate acute and chronic human schistosomiasis mansoni

Specific IgG and IgM responses to soluble egg antigen (SEA) and keyhole limpet haemocyanin (KLH) were measured by ELISA in patients with acute and chronic schistosomiasis. The tests based upon IgM and IgG antibodies responses to KLH presented the best diagnostic discrimination, and can be used in conjunction with clinical and epidemiological data to the differential diagnosis of acute schistosomiasis.

Studies on the production and regulation of interleukin, IL-13, IL-4 and interferon-gamma in human Schistosomiasis mansoni.

The production and regulation of interleukin (IL) IL-13, IL-4 and interferon-gamma was evaluated in different clinical forms of human schistosomiasis. The mechanisms of immune regulation are apparently different in the various clinical stages of the disease, some of them being antigen specific.

Enhanced interleukin-12 and CD40 ligand activities but reduced Staphylococcus aureus Cowan 1-induced responses suggest a generalized and progressively impaired type 1 cytokine pattern for human schistosomiasis.

Whole-blood-cell cultures from schistosomiasis patients were stimulated with a variety of T-cell-dependent and T-cell-independent stimuli to determine whether the defect in type 1 cytokine expression observed following helminth infection is associated with alterations in interleukin-12 (IL-12) or CD40 ligand (CD40L) responsiveness. Cultures from uninfected individuals produced abundant gamma interferon in response to Staphylococcus aureus Cowan 1 (SAC), while patients with intestinal and hepatosplenic disease displayed intermediate and weak responses, respectively. Importantly, the decrease in type 1 cytokine expression was not attributed to defects in IL-12- or CD40L-induced activity. Indeed, schistosomiasis patients displayed heightened responses and even produced more biologically active IL-12 when stimulated with SAC and CD40L than did uninfected controls. Finally, additional studies suggested only a partial role for IL-10, since intestinal patients were the only group that overproduced this downregulatory cytokine. Together, these studies demonstrate that the type 1 deficiency in chronic hepatosplenic schistosomiasis is not related to specific defects in IL-12, IL-10, or CD40L activity, although changes in the functional status of antigen-presenting cells appear to be involved.