Control of schistosomiasis pathology by combination of Sm28GST DNA immunization and praziquantel treatment.
(25/1591)
Today the control of schistosomiasis infection relies only on the use of praziquantel (PZQ) chemotherapy. However, PZQ treatment cannot prevent reinfection and progressive development of the pathology. We assessed in a mouse model the efficiency of a combined therapy, based on the combination of PZQ chemotherapy with Schistosoma mansoni 28-kDa glutathion S-transferase (Sm28GST) DNA vaccination, designed to limit the pathology. Following this combined therapy, the long-term survival of the mice was significantly enhanced in comparison with the survival of mice either vaccinated only or treated with PZQ only. In addition, the development of the pathology observed in the control groups was almost completely prevented in the vaccinated-PZQ-treated mice and was associated with a dramatic reduction of egg deposition in the tissues. We showed that PZQ treatment induced the unmasking of the native GST enzyme at the surface of the worms, thus permitting its neutralization by the antibodies raised by DNA immunization. This study provides insights into the synergistic mechanisms involved in an immunointervention strategy associated with chemotherapy for the control of a chronic infection and its associated pathology. (+info)
Effect of schistosomiasis and hepatitis on liver disease.
(26/1591)
Infection with hepatitis C virus (HCV) has become the most important public health problem in Egypt. In Egypt, viral hepatitis along with infection with Schistosoma mansoni is the major cause of chronic liver disease and liver cirrhosis. Although HCV infection is highly prevalent in Egypt, very little information is available on the distribution of the different genotypes of HCV. Our aims in this study were first to determine the prevalence of viral and parasite infections in patients with chronic liver disease and then to assess the distribution of HCV genotypes in these patients. In the present study, 151 individuals (50 with chronic liver disease, 51 with chronic diseases of organs other than the liver, and 50 apparently healthy persons) were investigated. The last 2 groups served as control groups. These individuals were subjected to routine liver function tests and detection of serum antibodies to bilharziasis, hepatitis B surface antigen (HBsAg), and HCV. Furthermore, the presence of hepatitis G virus (HGV) and HCV in the serum samples were tested for by a reverse transcription polymerase chain reaction (RT-PCR). Prevalence of different genotypes of HCV in patients positive for HCV were determined by RT-PCR using type-specific primers. Results of the study revealed that 84, 74, 12, and 20% of patients with chronic liver disease were positive for Schistosoma mansoni, HCV, HBsAg, and HGV, respectively, as compared to 51, 43.1, 2, and 4% of patients with other chronic diseases and 22, 6, 0, and 0% of apparently healthy individuals. One hundred percent of patients with chronic liver disease, 72.5% of those with other diseases, and 26% of normal controls were shown to have at least one of the studied infectious agents. Two or more of the agents were highly coincident in patients with chronic liver disease. In Egypt, HCV genotype 4a is highly prevalent, where it contributed 85% of the tested samples in comparison to 10, 2.5, and 2.5% for subtypes 1b, 2a, and 3a, respectively. In conclusion, these results suggest that in Egypt, HCV along with schistosomal parasite infection is the major risk factor for chronic liver disease. In most Egyptian patients, HCV genotype 4 is highly prevalent. (+info)
Evidence for a long-term effect of a single dose of praziquantel on Schistosoma mansoni-induced hepatosplenic lesions in northern Uganda.
(27/1591)
Treatment with praziquantel reduces the prevalence and intensity of Schistosoma mansoni infection. However, reversibility of periportal fibrosis of the liver, which potentially leads to fatal complications, is not unequivocally substantiated. In the Nile District of Uganda, 460 patients were parasitologically (Kato-Katz method) and ultrasonographically examined during October 1991, October 1992, and May 1994. Treatment with praziquantel at a dosage of 40 mg per kilogram of body weight was given in October 1991 and October 1992 to 460 individuals (group A). Another 192 patients were seen during the baseline study in October 1991 and missed the follow-up in October 1992 but took part in the second follow-up in May 1994. Thus, they received praziquantel only once in October 1991 (group B) and had an interval of 2.7 years until the next investigation in May 1994. Periportal thickening (PT) of the liver was assessed by ultrasound at each time point. Praziquantel therapy reduced the prevalence of S. mansoni in group A from 84% in 1991 to 31% in 1992 and 30% in 1994. The respective intensities of infection (geometric means of egg output) were 81 eggs per gram (epg) of stool in 1991, 31 epg in 1992, and 30 epg in 1994. Periportal thickening was found in 46% of patients in 1991, 32% of patients in 1992, and 35% of patients in 1994. Reversibility of PT was influenced by age (markedly lower reversibility in individuals older than 30 years) and sex (women and girls responded less favorably than did men and boys). Surprisingly, no significant difference was detected between group A and group B with respect to reversibility of PT The outcome between the 2 groups did not differ significantly. This may indicate that a single dose of praziquantel (as given to group B) may have a longer lasting effect than previously thought, that is, more than 2.5 years. (+info)
Resistance to praziquantel: direct evidence from Schistosoma mansoni isolated from Egyptian villagers.
(28/1591)
Recent evidence suggest that resistance to praziquantel (PZQ) may be developing. This would not be surprising in countries like Egypt where the drug has been used aggressively for more that 10 years. The classic phenotype of drug resistance is a significant increase in the 50% effective dose value of isolates retrieved from patients not responding to the drug. In a previous publication, we reported that such phenotypes have been isolated from humans infected with Schistosoma mansoni. Since the action of PZQ may be dependent upon the drug and host factors, most notably the immune system, we analyzed the quantitative effects of PZQ on single worms that differed in their response to PZQ when maintained in mice. Our hypothesis was that the in vitro action of the drug would correlate with it in vivo action. We confirmed this hypothesis and conclude that the in vitro action of the drug is related to its in vivo action. Knowing this relationship will assist in our ability to detect or survey for the PZQ resistant phenotype in human populations. (+info)
Application of immunodiagnostic assays: detection of antibodies and circulating antigens in human schistosomiasis and correlation with clinical findings.
(29/1591)
In an initial cross-sectional survey, serum, urine, and stool samples were collected from 370 participants representing about 10% of the population (n = 4,438) in Behbeet village, 50 km south of Cairo, Egypt, an area well known to be endemic solely for Schistosoma haematobium. Diagnosis was approached in two parallel ways. The first approach, which simulated actual conditions in many endemic areas in Egypt, was based on physical examination and urine and stool microscopic analysis. The second approach was based on two advanced immunodiagnostic assay systems. One system detected antibodies to species-specific microsomal antigens, the other detected circulating schistosomal antigens. Microsomal antigens from S. haematobium and S. mansoni were used to detect antibodies in the Falcon assay screening test (FAST)-ELISA and the enzyme-linked immunoelectrotransfer blot (EITB). Circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) were quantified in serum and urine samples in a sandwich ELISA using monoclonal antibodies. Parasitologically, the prevalence of S. haematobium was 7.01% in females and 25.82% in males, giving an overall prevalence of 15.8%. The combination of urine CCA and serum CAA for detecting circulating antigens and the combination of the S. haematobium adult worm microsomal antigens (HAMA) FAST-ELISA and the HAMA EITB for detecting antibodies significantly improved the sensitivity of detecting S. haematobium circulating antigens and antibodies. Also, including a medical examination as an integral part of field studies and correlating immunodiagnostic results with other clinical and investigational data allowed us to calculate an accurate estimation of S. haematobium prevalence in this area of low endemicity. (+info)
Short report: prevention of Schistosoma mansoni infections in mice by the insect repellents AI3-37220 and N,N-diethyl-3-methylbenzamide.
(30/1591)
N,N-diethyl-3-methylbenzamide (DEET) has recently been reported to kill cercariae of Schistosoma mansoni in vitro. In addition, it blocked cercarial entry into mouse tail skin. We confirmed these results and compared the efficacy of DEET to a second insect repellent, 1-(3-Cyclohexen-1-yl-carbonyl)-2-methylpiperidine (AI3-37220), in preventing S. mansoni infections in mice. Both AI3-37220 and DEET conferred 100% protection against S. mansoni infection via percutaneous exposure to cercariae. (+info)
Infection of mice lacking interleukin-7 (IL-7) reveals an unexpected role for IL-7 in the development of the parasite Schistosoma mansoni.
(31/1591)
A single intradermal administration of recombinant interleukin-7 (IL-7) has been shown to aggravate the course of murine schistosomiasis, to favor the development of Th2-associated antibodies specific for the parasite, and to alter migration kinetics and/or migratory route of the parasite within its vertebrate host. Here we show that after infection of IL-7-deficient mice with Schistosoma mansoni, the predominant parasite-specific humoral response follows a Th1 pattern, and the development of the parasite is greatly impaired. In IL-7-deficient mice, increased numbers of larvae reach the lungs and fewer larvae reach the liver, compared to control mice. In the absence of IL-7, female worms show an altered fecundity, leading to decreased numbers of eggs trapped in the tissues and to an amelioration of the pathology of the infected host. The most striking observation is the blockade of parasite growth in an IL-7-defective environment, leading to dwarf male and female worms. The results of this study have important implications for the role of IL-7 in the host-parasite relationship and show how parasites can disable or evade the host immune response. (+info)
Characterization of a stable form of tryptophan hydroxylase from the human parasite Schistosoma mansoni.
(32/1591)
A cDNA (Schistosoma mansoni tryptophan hydroxylase; SmTPH) encoding a protein homologous to tryptophan hydroxylase, the enzyme that catalyzes the rate-limiting step in the biosynthesis of serotonin, was cloned from the human parasite Schistosoma mansoni. Bacterial expression of SmTPH as a histidine fusion protein produced soluble active enzyme, which was purified to apparent homogeneity and a final specific activity of 0.17 micromol/min/mg of protein. The purified enzyme was found to be a tetramer of approximately 240 kDa with a subunit size of 58 kDa. Several of the biochemical and kinetic properties of SmTPH were similar to those of mammalian tryptophan hydroxylase. Unlike the mammalian enzyme, however, SmTPH was found to be stable at 37 degrees C, its t((1)/(2)) being nearly 23 times higher than that of a similarly expressed rabbit tryptophan hydroxylase. A semiquantitative reverse transcription polymerase chain reaction showed that the level of SmTPH mRNA in a larval stage of the parasite (cercaria) is 2.5 times higher than in adult S. mansoni, suggesting possible differences in the level of enzyme expression between the two developmental stages. This study demonstrates for the first time the presence of a functional tryptophan hydroxylase in a parasitic helminth and further suggests that the parasites are capable of synthesizing serotonin endogenously. (+info)