Schistosome Antigens Research Articles

Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on immune responses to schistosome antigens among the offspring: results of a randomised, placebo-controlled trial

BackgroundOffspring of women with schistosomiasis may exhibit immune responsiveness to schistosomes due to in utero sensitisation or trans-placental transfer of antibodies. Praziquantel treatment during pregnancy boosts maternal immune responses to schistosome antigens and reduces worm burden. Effects of praziquantel treatment during pregnancy on responses among offspring are unknown.MethodsIn a trial of anthelminthic treatment during pregnancy in Uganda (ISRCTN32849447; http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women with Schistosoma mansoni were examined for cytokine and antibody responses to schistosome worm (SWA) and egg (SEA) antigen, in cord blood and at age one year. Relationships to maternal responses and pre-treatment infection intensities were examined, and responses were compared between the offspring of women who did, or did not receive praziquantel treatment during pregnancy.ResultsOf 388 S. mansoni-infected women studied, samples were obtained at age one year from 215 of their infants. Stool examination for S. mansoni eggs was negative for all infants. Cord and infant samples were characterised by very low cytokine production in response to schistosome antigens with the exception of cord IL-10 responses, which were substantial. Cord and infant cytokine responses showed no association with maternal responses. As expected, cord blood levels of immunoglobulin (Ig) G to SWA and SEA were high and correlated with maternal antibodies. However, by age one year IgG levels had waned and were hardly detectable. Praziquantel treatment during pregnancy showed no effect on cytokine responses or antibodies levels to SWA or SEA either in cord blood or at age one year, except for IgG1 to SWA, which was elevated in infants of treated mothers, reflecting maternal levels. There was some evidence that maternal infection intensity was positively associated with cord blood IL-5 and IL-13 responses to SWA, and IL-5 responses to SEA, and that this association was modified by treatment with praziquantel.ConclusionsDespite strong effects on maternal infection intensity and maternal immune responses, praziquantel treatment of infected women during pregnancy had no effect on anti-schistosome immune responses among offspring by age one year. Whether the treatment will impact upon the offspring's responses on exposure to primary schistosome infection remains to be elucidated.Trial registrationISRCTN: ISRCTN32849447

High prevalence of persistent parasitic infections in foreign-born, HIV-infected persons in the United States.

BackgroundForeign-born, HIV-infected persons are at risk for sub-clinical parasitic infections acquired in their countries of origin. The long-term consequences of co-infections can be severe, yet few data exist on parasitic infection prevalence in this population.Methodology/Principal FindingsThis cross-sectional study evaluated 128 foreign-born persons at one HIV clinic. We performed stool studies and serologic testing for strongyloidiasis, schistosomiasis, filarial infection, and Chagas disease based on the patient's country of birth. Eosinophilia and symptoms were examined as predictors of helminthic infection. Of the 128 participants, 86 (67%) were male, and the median age was 40 years; 70 were Mexican/Latin American, 40 African, and 18 from other countries or regions. Strongyloides stercoralis antibodies were detected in 33/128 (26%) individuals. Of the 52 persons from schistosomiasis-endemic countries, 15 (29%) had antibodies to schistosome antigens; 7 (47%) had antibodies to S. haematobium, 5 (33%) to S. mansoni, and 3 (20%) to both species. Stool ova and parasite studies detected helminths in 5/85 (6%) persons. None of the patients tested had evidence of Chagas disease (n = 77) or filarial infection (n = 52). Eosinophilia >400 cells/mm3 was associated with a positive schistosome antibody test (OR 4.5, 95% CI 1.1–19.0). The only symptom significantly associated with strongyloidiasis was weight loss (OR 3.1, 95% CI 1.4–7.2).Conclusions/SignificanceGiven the high prevalence of certain helminths and the potential lack of suggestive symptoms and signs, selected screening for strongyloidiasis and schistosomiasis or use of empiric antiparasitic therapy may be appropriate among foreign-born, HIV-infected patients. Identifying and treating helminth infections could prevent long-term complications.

Human schistosomiasis is associated with endotoxemia and Toll-like receptor 2- and 4-bearing B cells.

Schistosomiasis is caused by parasitic trematodes. Individuals can accumulate hundreds of intravascular worms, which secrete a myriad of antigenic molecules into the bloodstream. Some of these molecules suppress immunity to microbial Toll-like receptor (TLR) ligands, such as lipopolysaccharides, which may increase host susceptibility to coinfecting pathogens. We show that schistosomiasis is associated with extremely high levels of endotoxemia as well as high mobility group 1, an endogenous inflammatory TLR ligand, in the absence of other coinfected pathogens. Circulating B cells express surface TLR2 and TLR4, reflecting systemic exposure to microbial ligands. Bacterial translocation may occur with schistosomal egg movement from the vascular to the gut and other routes, such as the skin during infection. Our report suggests that immunosuppressive schistosome antigens may have evolved to curb inflammatory responses to the high antigenic burden of translocated bacteria products and endogenous TLR ligands that arise during parasite exposure and inflammation.

Schistosoma mansoni Infections in Young Children: When Are Schistosome Antigens in Urine, Eggs in Stool and Antibodies to Eggs First Detectable?

BackgroundIn Uganda, control of intestinal schistosomiasis with preventive chemotherapy is typically focused towards treatment of school-aged children; the needs of younger children are presently being investigated as in lakeshore communities very young children can be infected. In the context of future epidemiological monitoring, we sought to compare the detection thresholds of available diagnostic tools for Schistosoma mansoni and estimate a likely age of first infection for these children.Methods and FindingsA total of 242 infants and preschool children (134 boys and 108 girls, mean age 2.9 years, minimum 5 months and maximum 5 years) were examined from Bugoigo, a well-known disease endemic village on Lake Albert. Schistosome antigens in urine, eggs in stool and host antibodies to eggs were inspected to reveal a general prevalence of 47.5% (CI95 41.1–54.0%), as ascertained by a positive criterion from at least one diagnostic method. Although children as young as 6 months old could be found infected, the average age of infected children was between 3¼–3¾ years, when diagnostic techniques became broadly congruent.ConclusionWhilst different assays have particular (dis)advantages, direct detection of eggs in stool was least sensitive having a temporal lag behind antigen and antibody methods. Setting precisely a general age of first infection is problematic but if present Ugandan policies continue, a large proportion of infected children could wait up to 3–4 years before receiving first medication. To better tailor treatment needs for this younger ageclass, we suggest that the circulating cathodic antigen urine dipstick method to be used as an epidemiological indicator.

Indian Schistosomes: A Need for Further Investigations

India is uniquely positioned with regard to schistosomes and schistosomiasis—discovering seven new mammalian species with the existence of three more schistosome species: Orientobilharzia turkestanicum, O. harinasutai, and Schistosoma haematobium(?). An endemic focus of urinary schistosomiasis was reported from Gimvi village of Ratnagiri, Maharashtra with infrequent occurrence of schistosome eggs in human stools. Cercarial dermatitis has been reported to be more abundant in rural population using ponds, tanks, and so forth, for their domestic purposes. Few dermatitis cases were tested positive by CHR. Schistosome antigen was also detected in urine of five cases suggesting existence of active schistosomiasis in India. Nevertheless, human kind does not appear to be the usual host for Indian schistosomes in contrast to S. haematobium, S. mansoni, or S. japonicum. Various reasons for this phenomenon are discussed including evolution of Indian schistosomes, immune mechanisms, and environmental conditions. These and other aspects such as seasonal effect on the prevalence, snail infectivity, heterologous mating, existence of hybrids, and number of schistosomes in heterologous infections need further investigations with application of molecular techniques. Joint efforts by the national as well as international scientific community would be much more rewarding for better understanding of the parasite and the infection.

The Immune Response to Schistosome Antigens in Formerly Infected Travelers

We investigated the type and strength of the immune response to schistosome antigens in a group of 20 Dutch travelers who had been infected with Schistosoma spp. during a group visit to Mali in 1991 and 8 non-infected controls. At the time, 9 had Katayama syndrome (KS), and 11 remained asymptomatic. All had been treated with praziquantel. Eight years later, serology remained positive in all 20 formerly infected travelers. The lymphocyte proliferative responses and cytokine responses (interleukin 13 [IL-13], IL-10, and interferon [IFN-γ] responses to soluble egg antigens and the IL-13, IL-10, and IL-5 response to adult worm antigen) were stronger in the travelers than in the controls and tended to be stronger in those with KS compared with those who had remained asymptomatic. In conclusion, Schistosoma infection induced a memory immune response, and people who experienced KS tended to have a stronger immune response to schistosome antigens than their asymptomatic counterparts.

Schistosomamansonitriggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses

The propensity of helminths, such as schistosomes, to immunomodulate the host's immune system is an essential aspect of their survival. Previous research has demonstrated how soluble schistosomal egg antigens (SEA) dampen TLR-signaling during innate immune responses. We show here that the suppressive effect by SEA on TLR signaling is simultaneously coupled to the activation of the Nlrp3 (NLR family, pyrin domain containing 3) inflammasome and thus IL-1β production. Therefore, the responsible protein component of SEA contains the second signal that is required to trigger proteolytic pro-IL-1β processing. Moreover, the SEA component binds to the Dectin-2/FcRγ (Fc receptor γ chain) complex and activates the Syk kinase signaling pathway to induce reactive oxygen species and potassium efflux. As IL-1β has been shown to be an essential orchestrator against several pathogens we studied the in vivo consequences of Schistosoma mansoni infection in mice deficient in the central inflammasome adapter ASC and Nlrp3 molecule. These mice failed to induce local IL-1β levels in the liver and showed decreased immunopathology. Interestingly, antigen-specific Th1, Th2, and Th17 responses were down-regulated. Overall, these data imply that component(s) within SEA induce IL-1β production and unravel a crucial role of Nlrp3 during S. mansoni infection.

Identification and characterization of immune complexes in the cerebrospinal fluid of patients with spinal cord schistosomiasis

The pathogenesis of neuroschistosomiasis is largely unknown. Available evidence suggests that it depends on the presence of parasite eggs in the nervous tissue and on the host's immune response. We investigated the presence of immune complexes (ICs) in the cerebrospinal fluid (CSF) of four patients with spinal cord schistosomiasis (SCS), and performed their characterization. ICs containing soluble egg antigen of Schistosoma mansoni (SEA) were found in the CSF of all the SCS patients. To our knowledge, this is the first evidence of ICs containing schistosomal antigens in the CSF of patients with SCS. Further studies are necessary to confirm our findings and investigate the possible roles of ICs in the pathogenesis of this disease.

Functional impairment of human myeloid dendritic cells during Schistosoma haematobium infection.

Chronic Schistosoma infection is often characterized by a state of T cell hyporesponsiveness of the host. Suppression of dendritic cell (DC) function could be one of the mechanisms underlying this phenomenon, since Schistosoma antigens are potent modulators of dendritic cell function in vitro. Yet, it remains to be established whether DC function is modulated during chronic human Schistosoma infection in vivo. To address this question, the effect of Schistosoma haematobium infection on the function of human blood DC was evaluated. We found that plasmacytoid (pDC) and myeloid DC (mDC) from infected subjects were present at lower frequencies in peripheral blood and that mDC displayed lower expression levels of HLA-DR compared to those from uninfected individuals. Furthermore, mDC from infected subjects, but not pDC, were found to have a reduced capacity to respond to TLR ligands, as determined by MAPK signaling, cytokine production and expression of maturation markers. Moreover, the T cell activating capacity of TLR-matured mDC from infected subjects was lower, likely as a result of reduced HLA-DR expression. Collectively these data show that S. haematobium infection is associated with functional impairment of human DC function in vivo and provide new insights into the underlying mechanisms of T cell hyporesponsiveness during chronic schistosomiasis.

CD23-bound IgE augments and dominates recall responses through human naïve B cells (130.3)

Abstract Peripheral blood human naïve B cells express high levels of CD23 and circulate pre-loaded with IgE. The antigen specificity of CD23-bound IgE presumably differs from the B cell receptor (BCR) and may reflect the antigen specific mix of free serum IgE. CD23-bound IgE is thought to enhance B cell antigen presentation raising the question of how a B cell might respond when presented with a variety of antigens and CD23-bound IgE specificities. We recently reported that an increase in CD23+ B cells is associated with resistance to schistosomiasis highlighting the potential importance of CD23-bound IgE in immunity. We sought to determine the relationship between BCR and CD23-bound IgE mediated B cell activation in schistosomiasis. Crude schistosome antigens downregulated basal B cell activation levels in individuals hyper-exposed to infectious worms. However, schistosome-specific IgE from resistant, occupationally exposed Kenyans recovered responses of naïve B cells to schistosome antigen. Furthermore, cross-linking of CD23 overrode intracellular signals mediated via the BCR illustrating its dominating role in B cell activation. Notably, the nature of the cognate antigen appeared to dictate the threshold of antigen-specific CD23-bound IgE required for B cell activation suggesting that CD23-bound IgE functions as a rheostat for B cell responses to antigenic stimuli. These results suggest that CD23-bound IgE augments and dominates host recall responses through naïve B cells.

Temporal Expression of Chemokines Dictates the Hepatic Inflammatory Infiltrate in a Murine Model of Schistosomiasis

Schistosomiasis continues to be an important cause of parasitic morbidity and mortality world-wide. Determining the molecular mechanisms regulating the development of granulomas and fibrosis will be essential for understanding how schistosome antigens interact with the host environment. We report here the first whole genome microarray analysis of the murine liver during the progression of Schistosoma japonicum egg-induced granuloma formation and hepatic fibrosis. Our results reveal a distinct temporal relationship between the expression of chemokine subsets and the recruitment of cells to the infected liver. Genes up-regulated earlier in the response included T- and B-cell chemoattractants, reflecting the early recruitment of these cells illustrated by flow cytometry. The later phases of the response corresponded with peak recruitment of eosinophils, neutrophils, macrophages and myofibroblasts/hepatic stellate cells (HSCs) and the expression of chemokines with activity for these cells including CCL11 (eotaxin 1), members of the Monocyte-chemoattractant protein family (CCL7, CCL8, CCL12) and the Hepatic Stellate Cell/Fibrocyte chemoattractant CXCL1. Peak expression of macrophage chemoattractants (CCL6, CXCL14) and markers of alternatively activated macrophages (e.g. Retnla) during this later phase provides further evidence of a role for these cells in schistosome-induced pathology. Additionally, we demonstrate that CCL7 immunolocalises to the fibrotic zone of granulomas. Furthermore, striking up-regulation of neutrophil markers and the localisation of neutrophils and the neutrophil chemokine S100A8 to fibrotic areas suggest the involvement of neutrophils in S. japonicum-induced hepatic fibrosis. These results further our understanding of the immunopathogenic and, especially, chemokine signalling pathways that regulate the development of S. japonicum-induced granulomas and fibrosis and may provide correlative insight into the pathogenesis of other chronic inflammatory diseases of the liver where fibrosis is a common feature.

Induction of Type 2 Responses by Schistosome Worms during Prepatent Infection

During natural schistosome infection, the induction of T helper type 2 (Th2) responses has been ascribed to parasite eggs, because exposure of the host to this life-cycle stage elicits a polarized Th2 response to egg antigens. In the present study, we show that schistosome worms also elicit systemic, antigen-specific type 2 responses during prepatent infection, before egg deposition begins. CD4(+) T cells producing interleukin (IL)-4 were induced by both male and female worms during single-sex infections, demonstrating that this response is independent of exposure to eggs. The Th2 response was accompanied by production of immunoglobulin E and the sensitization of circulating basophils to produce additional IL-4 in response to schistosome antigens. Together, our data show that schistosome worms establish an immunologic milieu where CD4(+) T cells and basophils are both primed to produce IL-4 before eggs are laid, suggesting that worms play a role in establishment of the Th2 response that is critical for host survival and parasite transmission.

Schistosoma mansoni infection reduces the incidence of murine cerebral malaria

BackgroundPlasmodium and Schistosoma are two of the most common parasites in sub-tropical areas. Deregulation of the immune response to Plasmodium falciparum, characterized by a Th1 response, leads to cerebral malaria (CM), while a Th2 response accompanies chronic schistosomiasis.MethodsThe development of CM was examined in mice with concomitant Schistosoma mansoni and Plasmodium berghei ANKA infections. The effect of S. mansoni egg antigen injection on disease development and survival was also determined. Cytokine serum levels were estimated using ELISA. Statistical analysis was performed using t-test.ResultsThe results demonstrate that concomitant S. mansoni and P. berghei ANKA infection leads to a reduction in CM. This effect is dependent on infection schedule and infecting cercariae number, and is correlated with a Th2 response. Schistosomal egg antigen injection delays the death of Plasmodium-infected mice, indicating immune involvement.ConclusionsThis research supports previous claims of a protective effect of helminth infection on CM development. The presence of multiple parasitic infections in patients from endemic areas should therefore be carefully noted in clinical trials, and in the development of standard treatment protocols for malaria. Defined helminth antigens may be considered for alleviation of immunopathological symptoms.

Hepatic stellate cells and parasite-induced liver fibrosis

Fibrogenesis is a common feature of many diseases where there is severe insult to the liver. The hepatic stellate cell trans-differentiation into a myofibroblast has been identified as an important event in liver fibrogenesis and has been well investigated over the last few years in a number of liver diseases. The trans-differentiation process can be monitored in vitro by evaluation of biomarkers that are characteristic of normal quiescent hepatic stellate cells or activated myofibroblasts. Two major parasitic diseases associated with liver injury and fibrosis are schistosomiasis and echinococcosis. Recent studies have highlighted a role for activated hepatic stellate cells in both murine and human schistosomiasis as well as demonstrating that schistosome antigens are able to regulate this trans-differentiation process. Study of the hepatic stellate cell and its interaction with parasite-derived antigens may be pivotal in our understanding of the pathology associated with schistosomiasis and other parasitic diseases, including echinococcosis, as well as revealing new information on the trans-differentiation process in this cell type.

Induction of helminth-specific IL-17 by dendritic cells exposed simultaneously to schistosome and bacterial antigens

Induction of helminth-specific IL-17 by dendritic cells exposed simultaneously to schistosome and bacterial antigens

Escherichia coli shares T- and B-lymphocyte epitopes with Schistosoma mansoni

In this study, we tested the cross-reaction between crude Escherichia coli antigen (ECA) and 3 crude Schistosoma mansoni antigens. The schistosomal antigens used were cercarial antigen preparation (CAP), soluble worm antigen preparation (SWAP), and soluble egg antigen (SEA). Four groups each of 3 mice received 2 intraperotineal immunizations with the above-mentioned antigens at a two-week interval. The dose of the ECA was 20 microg/100 microl PBS/mouse and that of any of the used schistosomal antigens was 50 microg/100 microl PBS/mouse. IgM and IgG reactivities and cross-reactivities were tested in individual immunized mice sera (IMS) against the above-mentioned antigens by ELISA and Western blotting. The changes in the B, CD4+ and CD8+ -T cells' counts post immunization were recorded. Priming with ECA caused significant increases in IgM (P<0.05) against CAP and SWAP, while both priming and boosting with ECA caused a significant elevation in the IgG only against SWAP. Priming and boosting with ECA or schistosomal antigens caused significant increases in IgM against ECA. Priming with ECA or SWAP caused significant elevation in IgG against ECA. In Western blotting, ECA-IMS recognized 16, 33, 38 and 94 kDa ECA peptides that cross-reacted with CAP-IMS. ECA peptides at 30 and 38 kDa cross-reacted among ECA, SWAP and SEA-IMS. CAP peptides at 40, 71, 85 and 97 kDa cross-reacted with ECA-IMS. A 59 kDa SWAP peptide cross-reacted with ECA. SEA peptides at approximately 55, 96 and 101 kDa cross-reacted with ECA-IMS. Immunization with ECA, CAP, SWAP or SEA caused significant increases in mesentric lymph nodes (MLN)-CD4+, CD8+ -T cells and MLN-B cells. For thymocytes, CD4+ -T cells significantly increased upon immunization with ECA and SWAP while CD8+-T cells significantly increased upon immunization with SWAP. It is necessary to include E. coli antigens as controls while establishing schistosomal antigens-based diagnostic tests to ensure the specificity of the detected immune responses. Characterization of the cross-reactive ECA antigens with protective potential against S. mansoni infection remains a future research objective.

Melatonin and schistosomal antigens ameliorate the anti-oxidative and biochemical response to Schistosoma mansoni infection in hamster

Abstract The present study was designed to investigate the potential protective effect of melatonin as an antioxidant separately or in combination with antigens (cercarial; CAP or soluble worm; SWAP) against Schistosoma mansoni infection in hamsters. Each hamster was sensitized with an initial immunization of 0.6 ml of the extracted antigen (30 μg protein/mL). After four days, a second injection of 0.4 mL was given (20 μg protein/mL). Then, each hamster was exposed to 260 ± 20 S. mansoni cercariae followed with melatonin treatment (3.5 mg/ kg) for thirty days from the 1st day of post infection. Levels of lipid peroxidation (LPO) products, catalase (CAT) activity, hepatic glutathione (GSH) and biochemical changes in the liver and kidneys functions were investigated. The results revealed a high significant increasing of LPO and decreasing of CAT and GSH in liver of infected hamsters. Biochemical observations showed severe damage in the liver enzyme activities and increasing cholesterol level in infected animals. Melatonin co-treatment with antigen to the infected-hamster attenuated the increase of LPO and restored the activity of CAT and levels of hepatic GSH. Also, the biochemical damages in the liver and kidneys functions were reduced. The present study suggests that melatonin may be useful in combating free radical-induced damage due to infection toxicity. The immunization with previous antigens resulted in a remarkable improvement on the liver enzyme activities, which were increased after infection. Thus, vaccination of hamsters with antigens (both CAP and SWAP) and melatonin treatment has more potent effect on the enhancement of antioxidant and biochemical of S. mansoni infected-hamster than each treatment separately. Immunization of the hamster with SWAP followed by melatonin was the best way among the other regime treatments to improve the biochemical and antioxidant parameters of the infected-hamsters.

Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on intensity of infection and antibody responses to schistosome antigens: results of a randomised, placebo-controlled trial

BackgroundPraziquantel treatment of schistosomiasis during pregnancy was only recommended in 2002; hence the effects of treatment during pregnancy are not fully known. We have therefore evaluated the effects on infection intensity and the immunological effects of praziquantel treatment against Schistosoma mansoni during pregnancy, compared with treatment after delivery.MethodsA nested cohort of 387 Schistosoma mansoni infected women was recruited within a larger trial of de-worming during pregnancy. Women were randomised to receive praziquantel or placebo during pregnancy. All women were treated after delivery. Infection intensity after treatment was assessed by a single Kato-Katz examination of stool samples with duplicate slides and categorised as undetected, light (1–99 eggs per gram (epg)), moderate (100–399 epg) or heavy (≥400 epg). Antibodies against S. mansoni worm and egg antigens were measured by ELISA. Results were compared between women first treated during pregnancy and women first treated after delivery.ResultsAt enrolment, 252 (65.1%) of the women had light infection (median (IQR) epg: 35 (11, 59)), 75 (19.3%) moderate (median (IQR) epg: 179(131, 227)) and 60 (15.5%) had heavy infection (median (IQR) epg: 749 (521, 1169)) with S. mansoni. At six weeks after praziquantel treatment during pregnancy S. mansoni infection was not detectable in 81.9% of the women and prevalence and intensity had decreased to 11.8% light, 4.7% moderate and 1.6% heavy a similar reduction when compared with those first treated after delivery (undetected (88.5%), light (10.6%), moderate (0.9%) and heavy (0%), p = 0.16). Parasite specific antibody levels were lower during pregnancy than after delivery. Praziquantel treatment during pregnancy boosted anti-worm IgG isotypes and to a lesser extent IgE, but these boosts were less pronounced than in women whose treatment was delayed until after delivery. Praziquantel had limited effects on antibodies against egg antigens.ConclusionS mansoni antigen-specific antibody levels and praziquantel-induced boosts in antibody levels were broadly suppressed during pregnancy, but this was not associated with major reduction in the efficacy of praziquantel. Long-term implications of these findings in relation to resistance to re-infection remain to be explored.Trial registrationInternational Standard Randomised Controlled Trial Number for the current study: ISRCTN32849447 http://www.controlled-trials.com/ISRCTN32849447/elliott

Pulmonary changes during acute experimental murine manson schistosomiasis

Dry cough, dyspnea and manifestations of bronchial asthma have recently been observed in patients with acute schistosomiasis. To investigate the type and pathogenesis of these conditions, an experimental mouse model for acute schistosomiasis was used. Forty mice were divided into four groups of ten each: three infected groups and a non-infected control group. The animals were examined 7, 28-35 and 40 days after exposure to cercariae. During the acute phase of the infection (28-35 days), a process of multifocal interstitial pneumonitis involving the peribronchial, peribronchiolar and subpleural tissues was found. This process was not seen during the other phases of the infection. Indirect immunofluorescence failed to demonstrate the presence of schistosomal antigens in the acute-phase lesions. The pneumonitis was attributed to products (inflammatory mediators) from acute-phase periovular necrotic-inflammatory lesions in the liver that were transported to the lungs by the bloodstream.

Effect of Praziquantel Treatment during Pregnancy on Cytokine Responses to Schistosome Antigens: Results of a Randomized, Placebo‐Controlled Trial

Praziquantel treatment of schistosomiasis boosts antischistosome responses, with type 2 helper T cell bias that may contribute to immunologically mediated killing and to protection against reinfection. Praziquantel treatment during pregnancy was recommended in 2002, but the immunological effects of the treatment had not been investigated. A cohort of 387 Schistosoma mansoni-infected women were recruited from a larger trial of deworming during pregnancy. Women were randomized to receive either praziquantel or placebo during pregnancy. Six weeks after delivery, all women received praziquantel. Cytokine responses to S. mansoni worm and egg antigens were measured in whole blood culture before and 6 weeks after each treatment. Schistosome-specific cytokine responses were suppressed during pregnancy. Praziquantel treatment during pregnancy caused significant boosts in interferon-gamma (IFN-gamma), interleukin (IL)-2, IL-4, IL-5, IL-13, and IL-10 responses to schistosome worm antigen and in IFN-gamma, IL-5, and IL-13 responses to schistosome egg antigen, but these boosts were not as substantial as those seen for women treated after delivery. Pregnancy suppresses a potentially beneficial boost in cytokine responses associated with praziquantel treatment. Further studies are needed on the long-term effects that treatment of schistosomiasis during pregnancy have on morbidity and resistance to reinfection among treated women and their offspring.