Schistosome Species Research Articles

Large CRISPR-Cas-induced deletions in the oxamniquine resistance locus of the human parasite Schistosoma mansoni.

Background. At least 250 million people worldwide suffer from schistosomiasis, caused by Schistosoma worms. Genome sequences for several Schistosoma species are available, including a high-quality annotated reference for Schistosoma mansoni. There is a pressing need to develop a reliable functional toolkit to translate these data into new biological insights and targets for intervention. CRISPR-Cas9 was recently demonstrated for the first time in S. mansoni, to produce somatic mutations in the omega-1 ( ω1) gene. Methods. We employed CRISPR-Cas9 to introduce somatic mutations in a second gene, SULT-OR, a sulfotransferase expressed in the parasitic stages of S. mansoni, in which mutations confer resistance to the drug oxamniquine. A 262-bp PCR product spanning the region targeted by the gRNA against SULT-OR was amplified, and mutations identified in it by high-throughput sequencing. Results. We found that 0.3-2.0% of aligned reads from CRISPR-Cas9-treated adult worms showed deletions spanning the predicted Cas9 cut site, compared to 0.1-0.2% for sporocysts, while deletions were extremely rare in eggs. The most common deletion observed in adults and sporocysts was a 34 bp-deletion directly upstream of the predicted cut site, but rarer deletions reaching as far as 102 bp upstream of the cut site were also detected. The CRISPR-Cas9-induced deletions, if homozygous, are predicted to cause resistance to oxamniquine by producing frameshifts, ablating SULT-OR transcription, or leading to mRNA degradation via the nonsense-mediated mRNA decay pathway. However, no SULT-OR knock down at the mRNA level was observed, presumably because the cells in which CRISPR-Cas9 did induce mutations represented a small fraction of all cells expressing SULT-OR. Conclusions. Further optimisation of CRISPR-Cas protocols for different developmental stages and particular cell types, including germline cells, will contribute to the generation of a homozygous knock-out in any gene of interest, and in particular the SULT-OR gene to derive an oxamniquine-resistant stable transgenic line.

Migratory routes, domesticated birds and cercarial dermatitis: the distribution of Trichobilharzia franki in Northern Iran.

Background: One of the major migration routes for birds going between Europe and Asia is the Black Sea-Mediterranean route that converges on the Volga Delta, continuing into the area of the Caspian Sea. Cercarial dermatitis is a disorder in humans caused by schistosome trematodes that use aquatic birds and snails as hosts and is prevalent in areas of aquaculture in Northern Iran. Before the disorder can be addressed, it is necessary to determine the etiological agents and their host species. This study aimed to document whether domestic mallards are reservoir hosts and if so, to characterize the species of schistosomes. Previous work has shown that domestic mallards are reservoir hosts for a nasal schistosome. Results: In 32 of 45 domestic mallards (Anas platyrhynchos domesticus) (71.1%), the schistosome Trichobilharzia franki, previously reported only from Europe, was found in visceral veins. Morphological and molecular phylogenetic analysis confirmed the species designation. These findings extend the range of T. franki from Europe to Eurasia. Conclusion: The occurrence of cercarial dermatitis in Iran is high in areas of aquaculture. Previous studies in the area have shown that domestic mallards are reservoir hosts of T. regenti, a nasal schistosome and T. franki, as shown in this study. The genetic results support the conclusion that populations of T. franki from Iran are not differentiated from populations in Europe. Therefore, the schistosomes are distributed with their migratory duck hosts, maintaining the gene flow across populations with compatible snail hosts in Iran.

Sexual Dysfunction and Infertility Amongst Spouses in Adamawa State, Nigeria

Deterioration in reproductive health and family food sufficiency leading to increase in marital crisis or divorce, arising from sexual dysfunction and infertility amongst spouses in Nigeria is alarming. An investigation was carried out to find the causes, signs and symptoms of sexual dysfunction and infertility amongst spouses in Adamawa State, Nigeria. Respondents were purposively selected with the use of questionnaires for oral interviews, observations and discussions. One hundred volunteer spouses were screened and sent to hospitals for diagnosis of reproductive diseases through culture of their urine, stool, vaginal swabs, semen and prostate content. These specimens were also examined under the electric microscope. Ultrasounds scanning of prostate glands, bladders, kidneys and ovaries or fallopian tubes of the spouses were also carried out to check for abnormalities. The results showed that, 88% of the spouses suffering from these conditions are youths (the active work force of the nation) between the ages of 20 to 40years while 12% are in the age bracket of 50 to 70years old. The findings indicated that, 90% of them are married while 10% are still single. The results showed that, 78% of the spouses had infection for 1 to 10years while 22% had it for more than 11years. The results showed that, 80% of them contracted the infection through sexual intercourse while 20% don’t know how and where they got infected. The hospital culture of urine, vaginal swabs, semen and prostate content of all the spouses showed negative results. The microscopic examinations of these specimens yielded positive to abdominal Schistosomiasis (bilharziasis). The ultrasound scanning of the prostate glands, kidneys and ovaries/ fallopian tubes revealed abnormalities of various degrees. Spouses with early or mild infections (for 1 to 10years) manifested the first 15 symptoms while those with severe and critical infections (for more than 11years) manifested all the 30 symptoms. Therefore, infections of the urinary bladders, genital organs, prostate glands and kidneys by Schistosome species contracted through sexual intercourse may be responsible for sexual dysfunction and infertility amongst spouses in the study area. There should be proper sensitivity for the diagnosis of mild infections caused by this parasite. Immediate authorities should, as a matter of urgency, initiate and support the development of a drug in commercial quantity that could be used to serve as an intervention programme in Nigeria and the world at large.

The genus Bilharziella vs. other bird schistosomes in snail hosts from one of the major recreational lakes in Poland

Bird schistosomes are commonly established as the causative agent of swimmer's itch − a hyper-sensitive skin reaction to the penetration of their infective larvae. The aim of the present study was to investigate the prevalence of the genus Bilharziella in comparison to other bird schistosome species from Lake Drawsko − one of the largest recreational lakes in Poland, struggling with the huge problem of swimmer's itch. In total, 317 specimens of pulmonate snails were collected and examined. The overall digenean infection was 35.33%. The highest bird schistosome prevalence was observed for Bilharziella sp. (4.63%) in Planorbarius corneus, followed by Trichobilharzia szidati (3.23%) in Lymnaea stagnalis and Trichobilharzia sp. (1.3%) in Stagnicola palustris. The location of Bilharziella sp. on the presented phylogeny showed that it is with high probability a different species than known so far B. polonica. Our finding complements the confirmed occurrence of bird schistosomes in European water bodies. Overall, presented research reveals the special importance of P. corneus as a source of the bird schistosome cercariae. This study suggests that the health threat connected with the blood flukes need to be further investigated by constant monitoring of their occurrence in intermediate hosts.

Avian schistosome species in Danish freshwater lakes: relation to biotic and abiotic factors.

Due to the increased prevalence of human infections with bird schistosome larvae (cercarial dermatitis) associated with bathing in Danish lakes, a nationwide survey of infected intermediate host snails was conducted in 2018-2020. Pulmonate snails (10,225 specimens) were collected from 39 freshwater lakes (in the four major geographic regions in Denmark) and subjected to shedding. Released schistosome cercariae were isolated and identified by polymerase chain reaction and sequencing whereby Trichobilharzia regenti, Trichobilharzia franki, Trichobilharzia szidati and Trichobilharzia anseri were recorded. Infections were primarily determined by biotic factors such as the presence of final host birds and intermediate host snails and water temperature was noted as an important abiotic parameter associated with the infection. No clear connection with other abiotic factors (conductivity, alkalinity, pH, nitrogen, phosphorous) was seen. The widespread occurrence of infected snails, when compared to previous investigations, suggests that climate changes at northern latitudes could be responsible for the increased risk of contracting cercarial dermatitis.

A systematic review and meta-analysis quantifying schistosomiasis infection burden in pre-school aged children (PreSAC) in sub-Saharan Africa for the period 2000-2020.

Following the adoption of the World Health Assembly Resolution WHA 65.21 and Neglected Tropical Diseases road map 2021-2030, schistosomiasis control programmes have shifted from morbidity control to disease elimination. However, several gaps continue to be observed in the implementation of control programmes with certain age groups omitted from these campaigns increasing health inequalities and risks of reinfections to previously treated groups. We used the Inverse Variance Heterogeneity (IVhet) model to estimate the prevalence of schistosomiasis infection among preschool-aged children. We did a systematic review of peer-reviewed literature on schistosomiasis in sub-Saharan Africa for the period January 1, 2000 to November 30, 2020. Quantitative data for cases of schistosomiasis infection were extracted, including country and region where the studies were done, year of publication and specific schistosome species observed. The IVhet model was used to estimate the pooled prevalence estimate (PPE), the heterogeneity and publication bias. We screened 2601 articles to obtain 47 eligible studies containing quantitative data on preschool-aged children. Of the selected studies, 44.7% (n = 22) were from East Africa while the least number of studies obtained (2.1%, n = 1) was from Central Africa. 21712 subjects were screened for infection due to Schistosoma spp; 13924 for S. mansoni and 7788 for S. haematobium. The PPE for schistosomiasis among PreSAC was 19% (95% CI: 11-28). Infection due to S. mansoni (IVhet PPE: 22% (95% CI: 9-36) was higher than that due to S. haematobium (15%; 95% CI: 6-25). A Luis Furuya-Kanamori index of 1.83 indicated a lack of publication bias. High level of heterogeneity was observed (I2 > 90%) and this could not be reduced through subgroup analysis. Schistosomiasis infection among pre-school aged children 6 years old and below is high. This indicates the importance of including this age group in treatment programmes to reduce infection prevalence and long-term morbidities associated with prolonged schistosome infection.

Association of TNF (rs1800629) promoter polymorphism and schistosomiasis with sub-microscopic asymptomatic Plasmodium falciparum infections in a schistosomiasis-endemic area in Zimbabwe.

Infection with Plasmodiumfalciparum parasites may result in a wide spectrum of symptoms ranging from asymptomatic to mild or severe. A number of factors are associated with this heterogeneous response to P.falciparum infection. In the present study, associations of sub-microscopic asymptomatic P.falciparum with Schistosoma species and TNF (rs1800629) polymorphism were investigated. 361 clinically healthy primary school children were microscopically screened for S.haematobium, S.mansoni and P.falciparum. Sub-microscopic asymptomatic P.falciparum infections were determined by PCR. Genotypic profiles were identified using ARMS-PCR. Logistic regression was used to assess the association of sub-microscopic asymptomatic P.falciparum with Schistosoma species and TNF (rs1800629) polymorphism. 17.2% of the children were infected with S.mansoni, and 27.4% were infected with S.haematobium. Microscopic examination of thick smears detected only one child infected with P.falciparum. Based on PCR results, 46.1% were infected with sub-microscopic asymptomatic P.falciparum. Children carrying heterozygous AG (OR: 16.964, 95% CI: 0.496-586.547) and homozygous GG (OR: 2.280, 95% CI: 0.111-46.796) genotypes of rs1800629 were associated with an increased likelihood of sub-microscopic asymptomatic P.falciparum infections compared with those carrying homozygous AA genotype. Children without S. haematobium infections (OR: 1.051, 95% CI: 0.146-8.985) and S. mansoni (OR: 2.658, 95% CI: 0.498-14.184) also had an increased likelihood (risk) of being infected with sub-microscopic asymptomatic P.falciparum compared with the Schistosoma-infected groups. However, all the associations observed were not statistical significant. No associations were observed between rs1800629 and schistosomiasis with sub-microscopic asymptomatic P.falciparum infections. This study also reports a high prevalence of sub-microscopic asymptomatic P.falciparum infection concomitant with low malaria transmission.

Large CRISPR-Cas-induced deletions in the oxamniquine resistance locus of the human parasite Schistosoma mansoni

Background. At least 250 million people worldwide suffer from schistosomiasis, caused by Schistosoma worms. Genome sequences for several Schistosoma species are available, including a high-quality annotated reference for Schistosoma mansoni. There is a pressing need to develop a reliable functional toolkit to translate these data into new biological insights and targets for intervention. CRISPR-Cas9 was recently demonstrated for the first time in S. mansoni, to produce somatic mutations in the omega-1 ( ω1) gene. Methods. We employed CRISPR-Cas9 to introduce somatic mutations in a second gene, SULT-OR, a sulfotransferase expressed in the parasitic stages of S. mansoni, in which mutations confer resistance to the drug oxamniquine. A 262-bp PCR product spanning the region targeted by the gRNA against SULT-OR was amplified, and mutations identified in it by high-throughput sequencing. Results. We found that 0.3-2.0% of aligned reads from CRISPR-Cas9-treated adult worms showed deletions spanning the predicted Cas9 cut site, compared to 0.1-0.2% for sporocysts, while deletions were extremely rare in eggs. The most common deletion observed in adults and sporocysts was a 34 bp-deletion directly upstream of the predicted cut site, but rarer deletions reaching as far as 102 bp upstream of the cut site were also detected. The CRISPR-Cas9-induced deletions, if homozygous, are predicted to cause resistance to oxamniquine by producing frameshifts, ablating SULT-OR transcription, or leading to mRNA degradation via the nonsense-mediated mRNA decay pathway. However, no SULT-OR knock down at the mRNA level was observed, presumably because the cells in which CRISPR-Cas9 did induce mutations represented a small fraction of all cells expressing SULT-OR. Conclusions. Further optimisation of CRISPR-Cas protocols for different developmental stages and particular cell types, including germline cells, will contribute to the generation of a homozygous knock-out in any gene of interest, and in particular the SULT-OR gene to derive an oxamniquine-resistant stable transgenic line.

A systematic review and meta-analysis on the rate of human schistosomiasis reinfection.

While praziquantel mass drug administration is currently the most widely used method in the control of human schistosomiasis, it does not prevent subsequent reinfection hence persistent transmission. Towards schistosomiasis elimination, understanding the reinfection rate is crucial in planning for the future interventions. However, there is scarcity of information on the global reinfection rate of schistosomiasis. This systematic review and meta-analysis aimed at summarizing studies that estimated the reinfection rate of human schistosomiasis. Three data bases (PubMed, Hinari and Google Scholar) were thoroughly searched to retrieve original research articles presenting data on reinfection rate of human schistosomiasis. Study quality and risk of bias was assessed based on Joanna Briggs Institute critical appraisal checklist. Meta-analysis was conducted using statistical R version 3.6.2 and R Studio using “meta” and “metafor” packages. Random effect model was employed to estimate pooled reinfection rates. Heterogeneity was determined using Cochran’s Q (chi-square)–test and Higgins I2 statistics. A total of 29 studies met inclusion criteria to be included in this review. All studies had at least satisfactory (5–9 scores) quality. The overal mean and pooled reinfection rates of schistosomiasis were 36.1% (±23.3%) and 33.2% (95% CI, 26.5–40.5%) respectively. For intestinal schistosomiasis, the mean and pooled reinfection rates were 43.9% (±20.6%) and 43.4% (95% CI, 35.8–51.4%), and that for urogenital schistosomiasis were 17.6% (±10.8%) and 19.4% (95% CI, 12.3%– 29.2%) respectively. Cochran’s Q (chi-square)–test and Higgins I2 statistic indicated significant heterogeneity across studies (p-values < 0.001, I2 values > 95%). Results of subgroup analysis showed that, the type of Schistosoma species, participants’ age group, sample size and geographical area had influence on disparity variation in reinfection rate of schistosomiasis (p < 0.1). Despite the control measures in place, the re-infection rate is still high, specifically on intestinal schistosomiasis as compared to urogenital schistosomiasis. Achieving 2030 sustainable development goal 3 on good health and wellbeing intensive programmatic strategies for schistosomiasis elimination should be implemented. Among such strategies to be used at national level are repeated mass drug administration at least every six months, intensive snails control and health education.

THE EFFECT OF GENISTEIN AGAINST SCHISTOSOMA MANSONI IN EXPERIMENTALLY INFECTED MICE

Schistosomiasis is one of the most significant parasites especially in tropics and subtropics.The only recognized drug used for treatment of all species of Schistosoma is praziquantel (PZQ).Worries about drug resistance motivated the quest for novel drug sources. Genistein, which is anatural product present in soybeans, was assessed for its antischistosomal effects in experimentallySchistosoma mansoni (S. mansoni) infected mice either solely or in association with PZQ.All groups that were infected subjected to portal and mesenteric veins perfusion, evaluation ofworm burden, liver and intestinal ova count, and the oogram. Moreover, ultrastructural changesin the worm’s tegument and interleukin IL-1β (IL-1β) levels in infected mice were also assessed.There were significant reductions in the total worm number and egg load of liver and intestinewith significant decrease in immature and mature eggs in all groups received treatment in comparisonwith the infected non treated control one. Tegument of adult worms exposed to genisteinexhibited distortion of suckers and erosions with loss of tubercles and spines. There was decreasein the IL-1β level in all treated groups. The best results, in all parameters, were given bycombined (genistein & PZQ) treatment. Genistein possessed moderate activity against S. mansoniadults and considered as a good adjuvant to PZQ.

THE EFFECT OF GENISTEIN AGAINST SCHISTOSOMA MANSONI IN EXPERIMENTALLY INFECTED MICE

Schistosomiasis is one of the most significant parasites especially in tropics and subtropics.The only recognized drug used for treatment of all species of Schistosoma is praziquantel (PZQ).Worries about drug resistance motivated the quest for novel drug sources. Genistein, which is anatural product present in soybeans, was assessed for its antischistosomal effects in experimentallySchistosoma mansoni (S. mansoni) infected mice either solely or in association with PZQ.All groups that were infected subjected to portal and mesenteric veins perfusion, evaluation ofworm burden, liver and intestinal ova count, and the oogram. Moreover, ultrastructural changesin the worm’s tegument and interleukin IL-1β (IL-1β) levels in infected mice were also assessed.There were significant reductions in the total worm number and egg load of liver and intestinewith significant decrease in immature and mature eggs in all groups received treatment in comparisonwith the infected non treated control one. Tegument of adult worms exposed to genisteinexhibited distortion of suckers and erosions with loss of tubercles and spines. There was decreasein the IL-1β level in all treated groups. The best results, in all parameters, were given bycombined (genistein & PZQ) treatment. Genistein possessed moderate activity against S. mansoniadults and considered as a good adjuvant to PZQ.

Immunology of Schistosomiasis

Background: Immunology studies include three main areas: infection, re-infection resistance to re-infection of schistosomiasis, and diagnosis. Objective: In this study, the author reports a study of immunology of schistosomiasis that focused on some important issues include mammalian host, important species of schistosomes, life cycle, host’s immune response, and diagnosis as objectives of this study. Methodology: The author searched Google, Science Direct and the PubMed Database of NCBI for articles on immunology of schistotomiasis published between 2009 and 2021. Articles were unrestricted open access, articles with permissions from Elsevier if required, and in English. Other relevant publications were also included. Results: Commonly, three Schistosoma species can infect humans. These include Schistosoma haematobium, Schistosoma japonicum, and Schistosoma mansoni. Schistosoma haematobium can infect such as baboons, humans, monkeys, and rhesus monkey. Schistosoma japonicum can infect such as humans, buffalos, dogs, and wild pigs. Schistosoma mansoni can infect humans and wild primates. The genus Schistosoma has two hosts: intermediate hosts and definite hosts. Intermediate hosts of S. haematobium, S. japonicum, and S. mansoni are the genus Bulinus, genus Oncomelania and genus Biomphalaria, respectively. In humans, cercariae released by intermediate hosts reach, and penetrate human skin. When cercariae reach human, it induce type 1 (Th1) immune responses and elevates such as IL-12 and TNFα. With worms reach adults, it induces Th2 immune response and elevates such as IL-4 and IL-13, and cause Th1 decrease. Increase of Th2 causes the development of hepatic granulomatous and fibrosis. Treatment can decrease Th2 and significantly hepatic granulomatous formation and fibrosis. In addition, it can reduce schistosomiasis cases. However, re-infection can occur in people who live in endemic areas. For diagnosing schistosomiasis, there are several tools can be used. These include such as microscopic and molecular tools. Conclusion: Th1 immune responses elevate serum cytokine levels such as IL-12 and TNFα. When Th1 is decreased, it elevates Th2 immune responses and level of cytokines such as IL-4 and TGF-β. This causes the development of granulomatous and fibrosis, even diseases such as cancer. Re-infection of schistomiasis can occur in people that have been treated, especially in the endemic areas. Tools for detecting schistosomiasis infection can include such as microscope and molecular methods.

Imported Schistosomiasis: A New Public Health Challenge for China.

Significantly increased imported schistosomiasis cases have been reported in China as the economy grows. The aim of this study is to review and summarize the current status, clinical features, and transmission risk of imported infections of Schistosoma mansoni and Schistosoma haematobium in China. A retrospective study was performed to review all information regarding the imported cases of schistosomiasis collected from published literature and the database of the National Notifiable Disease Report System from 1979 to 2019. The characterization of epidemiological and clinical features was analyzed. A total of 355 cases of imported schistosomiasis have been reported in 15 provinces (autonomous regions, municipalities) in China since 1979, including 78 cases of infection with S. mansoni (21.97%), 262 cases with S. haematobium (73.80%), and 15 cases with unidentified Schistosoma species. Eosinophilia was the most common sign of the infection with S. mansoni (91.03%). The parasitological findings were confirmed in 89.74% (70/78) of cases infected with S. mansoni and 32.06% (84/262) of cases infected with S. haematobium. There was no imported case of infection of Schistosoma japonicum, Schistosoma intercalatum, or Schistosoma mekongi reported in China during this period. Praziquantel is the best therapeutic drug for curing imported schistosomiasis. In addition, Biomphalaria straminea, the intermediate host of S. mansoni, has already been found in Guangdong province in south China. There is a rising risk that the existence of the intermediate host B. straminea and the imported cases of S. mansoni infection could cause the spread of the infections and make these endemic. Thus, better understanding of the clinical features and the transmission pattern of these Schistosoma infections would assist Chinese physicians in the diagnosis and treatment of these imported schistosomiasis cases.

Evaluation of the therapeutic efficacy of praziquantel against schistosomes in seven countries with ongoing large-scale deworming programs

The World Health Organization (WHO) recommends periodic assessment of the therapeutic efficacy of praziquantel (PZQ) to detect reduced efficacy that may arise from drug resistance in schistosomes. In this multi-country study (2014), we assessed the therapeutic efficacy of a single oral dose of PZQ (40 mg/kg) against Schistosoma mansoni (Brazil, Cameroon, Ethiopia, Mali, Madagascar and Tanzania), S. haematobium (Cameroon, Ethiopia, Mali, Tanzania and Zanzibar) and S. japonicum (the Philippines) infections in school-aged children, across a total of 12 different trials. Each trial was performed according to the standardized methodology for evaluating PZQ efficacy as described by the WHO. Overall, therapeutic efficacy, measured as the reduction in arithmetic mean of schistosome egg counts following drug administration (egg reduction rate; ERR), was high for all three schistosome species (S. mansoni: 93.4% (95%CI: 88.8–96.8); S. haematobium: 97.7% (95%CI: 96.5–98.7) and S. japonicum: 90.0% (95%CI: 68.4–99.3). At the trial level, therapeutic efficacy was satisfactory (point estimate ERR ≥90%) for all three Schistosoma species with the exception of S. mansoni in Cameroon where the ERR was 88.5% (95%CI: 79.0–95.1). Furthermore, we observed that in some trials individual drug response could vary significantly (wide 95%CI) and that few non-responsive individuals could significantly impact ERR point estimates. In conclusion, these results do not suggest any established reduced efficacy of the standard PZQ treatment to any of the three schistosome species within these countries. Nevertheless, the substantial degree of variation in individual responses to treatment in some countries underpins the need for future monitoring. The reported ERR values serve as reference values to compare with outcomes of future PZQ efficacy studies to ensure early detection of reduced efficacies that could occur as drug pressure continues increase. Finally, this study highlights that 95%CI should be considered in WHO guidelines to classify the therapeutic efficacy of PZQ.

Spinal neuroschistosomiasis caused by Schistoma mansoni: cases reported in two brothers

BackgroundSpinal neuroschistosomiasis (SN) is one of the most severe clinical presentations of schistosomiasis infection and an ectopic form of the disease caused by any species of Schistosoma. In Brazil, all cases of this clinical manifestation are related to Schistosoma mansoni, the only species present in the country. Although many cases have been reported in various endemic areas in Brazil, this is the first time in the literature that SN is described in two brothers.Case presentationTwo cases of SN were accidentally diagnosed during an epidemiological survey in an urban area endemic for schistosomiasis transmission. Both patients complained of low back pain and muscle weakness in the lower limbs. Sphincter dysfunction and various degrees of paresthesia were also reported. The patients’ disease was classified as hepato-intestinal stage schistosomiasis mansoni at the onset of the chronic form. A positive parasitological stool test for S. mansoni, clinical evidence of myeloradicular damage and exclusion of other causes of damage were the basic criteria for diagnosis. After treatment with praziquantel and corticosteroid, the patients presented an improvement in symptoms, although some complaints persisted.ConclusionsIt is important to consider SN when patients come from areas endemic for transmission of schistosomiasis mansoni. Clinical physicians and neurologists should consider this diagnostic hypothesis, because recovery from neurological injuries is directly related to early treatment. As, described here in two brothers, a genetic predisposition may be related to neurological involvement. Primary care physicians should thus try to evaluate family members and close relatives in order to arrive at prompt schistosomiasis diagnosis in asymptomatic individuals and propose treatment in an attempt to avoid progression to SN.

Schistosomiasis infections in South African pregnant women: A review.

Schistosomiasis, a chronic parasitic disease caused by Schistosoma species, has a negative impact on pregnancy outcomes and child development. The disease affects over 230 million people worldwide, and in South Africa an estimated 5.2 million people are thought to be infected. However, there is scant data on the impact of schistosomiasis in pregnancy in South Africa and globally. The aim of this review was to analyse the current knowledge of schistosomiasis in pregnancy, particularly in South Africa, focusing on maternal and neonatal complications linked directly to the disease or its treatment. An electronic search of online databases was used to identify and collect relevant research articles related to schistosomiasis in pregnancy, with a focus on South Africa. Schistosomiasis can cause severe organ damage when left untreated and influences maternal and foetal morbidity and mortality. Although South Africa's first helminth control programme was established in 1997, there is currently no ongoing treatment strategy programme, and little information is available on prevalence rates in pregnant women for the last 20 years. There is also an absence of data from well-controlled clinical trials that focus on the efficacy and safety of treatment during pregnancy, which has led to this vulnerable group being neglected. This review highlights the dearth of information on the impact of schistosomiasis in pregnant women in South Africa and the need for high-quality evidence-based studies.

Comparing PCR techniques against conventional cercarial shedding methods for detecting Schistosoma mansoni infection in Biomphalaria snails

The detection of Schistosoma mansoni infection in both its intermediate (snail) and definitive (human) hosts is useful in providing information on the transmission of schistosomiasis. Three pairs of previously designed PCR primers (SM1-7, SMF/R & ND5) used for the detection of S. mansoni infection were tested. We assess the utility of each of these primer sets for detecting S. mansoni infection both in artificially exposed laboratory bred Biomphalaria glabrata, and field infected African Biomphalaria sudanica and Biomphalaria pfeifferi. Two of the three primer sets (SMF/R & ND5) detected S. mansoni infection in snails, but amplification of S. mansoni DNA with SM1-7 was unreliable. For the artificially exposed laboratory bred B. glabrata snails, SMF/R and ND5 both detected infection in more snails than the cercarial shedding method. Infection detection rates were 62.4% for ND5, 57.1% for SMF/R and 50.4% using traditional cercarial shedding methods. Both SMF/R and ND5 detected S. mansoni infection in 91% of snails observed shedding cercariae, increasing to 98.5% when low stringency PCR methods were used. When comparing each of the detection methods using a Bayesian latent class analysis model, ND5 had the highest detection sensitivity and negative predictive value (NPV), while SMF/R had the highest detection specificity and positive predictive value (PPV). In field collected Biomphalaria snails, ND5 detected S. mansoni infection in 21 of 24 snails categorised as shedding S. mansoni cercariae and 4 of 24 snails categorised as shedding non-S. mansoni cercariae, while SMF/R detected infection in 18 of 24 snails categorised as shedding S. mansoni cercariae and in 3 of 24 snails categorised as shedding non-S. mansoni cercariae. All SMF/R and ND5 PCR products were shown to be S. mansoni indicating that these field snails must have been infected with both S. mansoni and cercariae from other Schistosoma species. This indicates that the two primer sets are specific for S. mansoni and will not amplify non-S. mansoni species when used at their recommended annealing temperatures. Both the SMF/R and ND5 primers effectively detected S. mansoni infection in three Biomphalaria species and have improved detection sensitivity over cercarial shedding.

A comparative proteomics analysis of the egg secretions of three major schistosome species

Morbidity associated with hepatic and urogenital schistosomiasis stems primarily from the host immune response directed against schistosome eggs. When eggs become entrapped in host tissues, the development of fibrotic plaques drives downstream pathology. These events occur due to the antigenic nature of egg excretory/secretory products (ESPs). Both Schistosoma mansoni and S. japonicum ESPs have been shown to interact with several cell populations in the host liver including hepatocytes, macrophages, and hepatic stellate cells, with both immunomodulatory and pathological consequences. Several protein components of the ESPs of S. mansoni and S. japonicum eggs have been characterised; however, studies into the collective contents of schistosome egg ESPs are lacking. Utilising shotgun mass spectrometry and an array of in silico analyses, we identified 266, 90 and 50 proteins within the S. mansoni, S. japonicum and S. haematobium egg secretomes respectively. We identified numerous proteins with already established immunomodulatory activities, vaccine candidates and vesicle markers. Relatively few common orthologues within the ESPs were identified by BLAST, indicating that the three egg secretomes differ in content significantly. Having a clearer understanding of these components may lead to the identification of new proteins with uncharacterised immunomodulatory potential or pathological relevance. This will enhance our understanding of host-parasite interactions, particularly those occurring during chronic schistosomiasis, and pave the way towards novel therapeutics and vaccines.

Duplex real-time PCR for sexing Schistosoma japonicum cercariae based on W chromosome-specific genes and its applications.

As a unique feature among otherwise hermaphroditic trematodes, Schistosoma species are gonochoric parasites whose sex is genetically determined (ZZ for males and ZW for females). However, schistosome larvae are morphologically identical, and sex can only be discriminated by molecular methods. Here, we integrated published Schistosoma. japonicum transcriptome and genome data to identify W chromosome-specific genes as sex biomarkers. Three W chromosome-specific genes of S. japonicum were identified as sex biomarkers from a panel of 12 genes expressed only in females. An efficient duplex real-time PCR (qPCR) method for sexing cercariae was developed which could identify the sex of cercariae within 2 h without DNA extraction. Moreover, this method can be used to identify not only single-sex but also mixed-sex schistosome-infected snails. We observed a nearly equal proportion of single-male, single-female, and mixed-sex schistosome infections in artificially infected snails. Sex-known schistosome-infected snail models can be efficiently constructed with the aid of duplex qPCR. A field study revealed that single-sex schistosome infections were predominant among naturally infected snails. Finally, a schistosomiasis mouse model based on sex-known cercariae infection was shown to be more reliable than a model based on sex-unknown cercariae infection. The developed duplex qPCR method for sexing S. japonicum cercariae can be widely used for schistosomiasis modeling, genetic experiments, and field-based molecular epidemiological studies.

An iterative process produces oxamniquine derivatives that kill the major species of schistosomes infecting humans.

Currently there is only one method of treatment for human schistosomiasis, the drug praziquantel. Strong selective pressure has caused a serious concern for a rise in resistance to praziquantel leading to the necessity for additional pharmaceuticals, with a distinctly different mechanism of action, to be used in combination therapy with praziquantel. Previous treatment of Schistosoma mansoni included the use of oxamniquine (OXA), a prodrug that is enzymatically activated in S. mansoni but is ineffective against S. haematobium and S. japonicum. The oxamniquine activating enzyme was identified as a S. mansoni sulfotransferase (SmSULT-OR). Structural data have allowed for directed drug development in reengineering oxamniquine to be effective against S. haematobium and S. japonicum. Guided by data from X-ray crystallographic studies and Schistosoma worm killing assays on oxamniquine, our structure-based drug design approach produced a robust SAR program that tested over 300 derivatives and identified several new lead compounds with effective worm killing in vitro. Previous studies resulted in the discovery of compound CIDD-0066790, which demonstrated broad-species activity in killing of schistosome species. As these compounds are racemic mixtures, we tested and demonstrate that the R enantiomer CIDD-007229 kills S. mansoni, S. haematobium and S. japonicum better than the parent drug (CIDD-0066790). The search for derivatives that kill better than CIDD-0066790 has resulted in a derivative (CIDD- 149830) that kills 100% of S. mansoni, S. haematobium and S. japonicum adult worms within 7 days. We hypothesize that the difference in activation and thus killing by the derivatives is due to the ability of the derivative to fit in the binding pocket of each sulfotransferase (SmSULT-OR, ShSULT-OR, SjSULT-OR) and to be efficiently sulfated. The purpose of this research is to develop a second drug to be used in conjunction with praziquantel to treat the major human species of Schistosoma. Collectively, our findings show that CIDD-00149830 and CIDD-0072229 are promising novel drugs for the treatment of human schistosomiasis and strongly support further development and in vivo testing.