Repeated Praziquantel Treatment Research Articles

Baseline Liver Ultrasound Findings in Preschool Children From the Praziquantel in Preschoolers Trial in Lake Albert, Uganda.

Periportal fibrosis is a late-stage manifestation of chronic infection with Schistosoma mansoni . Praziquantel (PZQ), the only drug available for the treatment of schistosomiasis, has limited effect in treating established morbidity. Preschool-age children (PSAC) are not considered to be an at-risk population for severe morbidity. However, the prevalence of periportal fibrosis in PSAC in S. mansoni endemic settings is unknown. As part of a phase II clinical trial comparing different dosing regimens of PZQ in children age 12-47 months infected with S. mansoni in Uganda ("praziquantel in preschoolers" trial), we present baseline results assessing liver ultrasound (US) findings as per the WHO Niamey Protocol. A total of 7/347 (2%) PSAC had Image Pattern C with pipe stems and echogenic rings suggestive of periportal fibrosis, 29/347 (8%) had Image Pattern B and 58 (17%) had evidence of periportal thickening There were higher adjusted odds of periportal thickening with older age [odds ratio (OR): 1.04; 95% confidence interval (CI): 1.00-1.07], primary maternal education (OR: 1.04; 95% CI: 1.00-1.07) and being taken to the lake weekly (OR: 3.02; 95% CI: 1.19-7.63). A further 44/347 children (13%) had a rounded caudal liver edge which was associated with high S. mansoni infection intensity (adjusted OR: 3.31; 95% CI: 1.46-7.51). Incipient schistosomiasis-related liver morbidity was detected in young children enrolled in the praziquantel in preschoolers trial. Adequate age-adjusted reference measurements for liver ultrasound findings in very small children are lacking but urgently needed. Schistosomiasis-related fibrosis may be delayed or averted with early and repeated PZQ treatment.

Association between the Number of Repeated Praziquantel Treatments and Kidney Parenchymal Change in Northeast Thailand.

In Northeast Thailand, Praziquantel (PZQ) is used to treat infection with the Opisthorchis viverrnini (OV). OV has highly prevalence in this area due to the traditional consumption of uncooked cyprinid fish. The nephrotoxic effects of PZQ metabolite excretion through the kidney have not been assessed yet. This study investigated the relationship between number of Praziquantel treatments and kidney parenchymal change. A study was carried out on participants from the Cholangiocarcinoma Screening and Care Program (CASCAP) between 2013 - 2018. The frequency of PZQ use was reported using a standardized questionnaire. Kidney parenchymal change (KPC) was defined as having a kidney abnormality based on ultrasonography diagnosed by well-trained general practitioners. Adjusted odds ratios (ORs) measured associations between PZQ frequency and KPC controlling for the effects of other extraneous factors using multiple logistic regression. A total of 490,969 subjects with mean age of 55.2 (SD = 9.15) years were enrolled among them 62.1% were female. Prevalence of KPC was 1.2% while prevalence of KPC were 1.2%, 1.3%, 1.4%, and 1.5% for participants with one, two, three, and more than 3 PZQ treatment occasions respectively. Those dose-response relationship was statistically significant based on chi-square test for trend (p-value <0.001). After controlling for possible confounders, compared to non-treatment, subjects with more than 3 treatment occasions were 25% more likely to have a KPC positive result (OR = 1.25; 95% CI: 1.02 - 1.52; p-value = 0.028). The number of repeated PZQ treatments is statistically significantly related to KPC. This relationship could be included in health messaging for those who continue eating uncooked fish with an understanding that the OV infection can easily be cured by PZQ without any other health concerns. For positive OV cases, however, the known efficacy of PZQ could over-ride the small magnitude of the adverse effect.

Change in schistosomiasis-related liver disease with repeated praziquantel treatment in school children in rural Zambia.

Repeated praziquantel treatment for schistosomiasis is an effective method to reduce disease burden. Ultrasonographic methods were used to assess the severity of schistosoma mansoni-related liver disease and demonstrate improvement following treatment. We compared data from 733 children in 2010 and 972 children in 2018 to determine the effect of repeated praziquantel treatment on prevalence of liver disease. Three age groups were compared across three liver disease classifications (normal, mild, severe). From 2010 to 2018, there was a significant reduction in prevalence of severe liver disease in all age groups (P = 0.03 for 5-10 years, P < 0.001 for 11-15 years and 16-20 years). In both male and female students, the proportion having a normal liver significantly increased (P < 0.001) from 2010 to 2018, in the 11-15-year-olds and 16-20-year-olds, demonstrating that liver disease significantly reduced in these age groups. This study demonstrates a reduction in schistosomiasis-related morbidity with repeated praziquantel treatment.

Efficacy of single versus four repeated doses of praziquantel against Schistosoma mansoni infection in school-aged children from Côte d'Ivoire based on Kato-Katz and POC-CCA: An open-label, randomised controlled trial (RePST).

BackgroundPreventive chemotherapy with praziquantel (PZQ) is the cornerstone of schistosomiasis control. However, a single dose of PZQ (40 mg/kg) does not cure all infections. Repeated doses of PZQ at short intervals might increase efficacy in terms of cure rate (CR) and intensity reduction rate (IRR). Here, we determined the efficacy of a single versus four repeated treatments with PZQ on Schistosoma mansoni infection in school-aged children from Côte d’Ivoire, using two different diagnostic tests.MethodsAn open-label, randomized controlled trial was conducted from October 2018 to January 2019. School-aged children with a confirmed S. mansoni infection based on Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA) urine cassette test were randomly assigned to receive either a single or four repeated doses of PZQ, administered at two-week intervals. The primary outcome was the difference in CR between the two treatment arms, measured by triplicate KK thick smears 10 weeks after the first treatment. Secondary outcomes included CR estimated by POC-CCA, IRR by KK and POC-CCA, and safety of repeated PZQ administration.Principal findingsDuring baseline screening, 1,022 children were assessed for eligibility of whom 153 (15%) had a detectable S. mansoni infection, and hence, were randomized to the standard treatment group (N = 70) and the intense treatment group (N = 83). Based on KK, the CR was 42% (95% confidence interval (CI) 31–52%) in the standard treatment group and 86% (95% CI 75–92%) in the intense treatment group. Observed IRR was 72% (95% CI 55–83%) in the standard treatment group and 95% (95% CI 85–98%) in the intense treatment group. The CR estimated by POC-CCA was 18% (95% CI 11–27%) and 36% (95% CI 26–46%) in the standard and intense treatment group, respectively. Repeated PZQ treatment did not result in a higher number of adverse events.Conclusion/significanceThe observed CR using KK was significantly higher after four repeated treatments compared to a single treatment, without an increase in adverse events. Using POC-CCA, the observed CR was significantly lower than measured by KK, indicating that PZQ may be considerably less efficacious as concluded by KK. Our findings highlight the need for reliable and more accurate diagnostic tools, which are essential for monitoring treatment efficacy, identifying changes in transmission, and accurately quantifying the intensity of infection in distinct populations. In addition, the higher CR in the intense treatment group suggests that more focused and intense PZQ treatment can help to advance schistosomiasis control.Trial registrationwww.clinicaltrials.gov NCT02868385.

Two-year longitudinal survey reveals high genetic diversity of Schistosoma mansoni with adult worms surviving praziquantel treatment at the start of mass drug administration in Uganda

BackgroundA key component of schistosomiasis control is mass drug administration with praziquantel. While control interventions have been successful in several endemic regions, mass drug administration has been less effective in others. Here we focus on the impact of repeated praziquantel treatment on the population structure and genetic diversity of Schistosoma mansoni.MethodsWe examined S. mansoni epidemiology, population genetics, and variation in praziquantel susceptibility in parasites isolated from children across three primary schools in a high endemicity region at the onset of the Ugandan National Control Programme. Children were sampled at 11 timepoints over two years, including one week and four weeks post-praziquantel treatment to evaluate short-term impacts on clearance and evidence of natural variation in susceptibility to praziquantel.ResultsPrevalence of S. mansoni was 85% at baseline. A total of 3576 miracidia larval parasites, isolated from 203 individual children, were genotyped at seven loci. Overall, genetic diversity was high and there was low genetic differentiation, indicating high rates of parasite gene flow. Schistosome siblings were found both pre-treatment and four weeks post-treatment, demonstrating adult worms surviving treatment and natural praziquantel susceptibility variation in these populations at the beginning of mass drug administration. However, we did not find evidence for selection on these parasites. While genetic diversity decreased in the short-term (four weeks post-treatment), diversity did not decrease over the entire period despite four rounds of mass treatment. Furthermore, within-host genetic diversity was affected by host age, host sex, infection intensity and recent praziquantel treatment.ConclusionsOur findings suggest that praziquantel treatments have short-term impacts on these parasite populations but impacts were transient and no long-term reduction in genetic diversity was observed. High gene flow reduces the likelihood of local adaptation, so even though parasites surviving treatment were observed, these were likely to be diluted at the beginning of the Ugandan National Control Programme. Together, these results suggest that MDA in isolation may be insufficient to reduce schistosome populations in regions with high genetic diversity and gene flow.

Multiple Praziquantel Treatments of Schistosoma mansoni Egg-Negative, CCA-Positive Schoolchildren in a Very Low Endemic Setting in Egypt Do Not Consistently Alter CCA Results.

.Forty-four Schistosoma mansoni egg-negative/circulating cathodic antigen (CCA) low-positive (trace or 1+) children in three districts of very low prevalence in Egypt were given three sequential praziquantel (PZQ) treatments. Stool and urine specimens were collected 3 months following the initial treatment, and 3 weeks following the second and following the third PZQ treatments, which were conducted 5 weeks apart. Stool specimens were examined by Kato–Katz (four slides/stool sample) and all S. mansoni egg-negative stools were further tested by the “miracidia hatching test” (MHT). Urine samples were examined by the point-of-care CCA assay (POC-CCA). Over the study period, all stool samples from study subjects remained S. mansoni egg negative and MHT negative. Of the POC-CCA test results, in the first day of the study 3 months following the initial treatment, 29.5% were negative, 61.4% CCA trace positives, and 9.1% CCA 1+ positives. Following each PZQ treatment, the test results fluctuated between 1+, trace, and negative, but did not consistently decrease. The proportions of POC-CCA–positive results obtained in the first day (70.5%) as compared with the last day of the study (72.7%) in all of the three districts were very similar. We conclude that CCA trace and 1+ readings, in Kato–Katz S. mansoni egg-negative children in this area with very low levels of intestinal schistosomiasis, are not consistently altered or rendered consistently negative following repeated PZQ treatments and are therefore likely to represent false-positive readings. This finding is of critical importance for countries such as Egypt as they approach elimination.

Repeated praziquantel treatment and Opisthorchis viverrini infection: a population-based cross-sectional study in northeast Thailand

BackgroundOpisthorchis viverrini infection is highly prevalent in northeast Thailand. This liver fluke is classified as a carcinogen due to its causal links with cholangiocarcinoma (CCA) development. Although treatment with praziquantel (PZQ) effectively cures O. viverrini infection, the prevalence remains high due to the traditional consumption of raw fish. Therefore, re-infection is common in the endemic community, leading to severe hepato-biliary morbidities including the fatal CCA. In this study, we evaluate the association between the frequency of previous PZQ treatment and current O. viverrini infections among Thai adults living in the endemic area of northeast Thailand.MethodsThis study includes all participants who were screened for O. viverrini infection in the Cholangiocarcinoma Screening and Care Program (CASCAP), northeast Thailand. History of PZQ treatment was recorded using a health questionnaire. O. viverrini infections were diagnosed using urine antigen detection. Associations between PZQ and O. viverrini were determined by adjusted odds ratio (aOR) and 95% confidence interval (CI) using multiple logistic regression.ResultsAmong participants, 27.7% had previously been treated once with PZQ, 8.2% twice, 2.8% three times, and 3.5% more than three times. Current O. viverrini prevalence was 17% (n = 524). Compared with participants who never used PZQ, the aOR for infection among those who used the drug once was 1.09 (95% CI: 0.88–1.37), twice was 1.19 (95% CI: 0.85–1.68), three times was 1.28 (95% CI: 0.74–2.21), and more than three times was 1.86 (95% CI: 1.18–2.93; P = 0.007).ConclusionsThe population with a frequent history of PZQ use and still continued raw fish consumption showed high levels of repeated reinfection with O. viverrini. They were infected, treated and re-infected repeatedly. These findings suggest that certain participants continue raw fish consumption even after previous infection. This is a particular problem in highly endemic areas for O. viverrini and increases the risk of CCA.

Repeated doses of Praziquantel in Schistosomiasis Treatment (RePST) \u2013 single versus multiple praziquantel treatments in school-aged children in C\xf4te d\u2019Ivoire: a study protocol for an open-label, randomised controlled trial

BackgroundLarge scale administration of the anthelminthic drug praziquantel (PZQ) to at-risk populations is the cornerstone of schistosomiasis control, although persisting high prevalence of infections in some areas and growing concerns of PZQ resistance have revealed the limitations of this strategy. Most studies assessing PZQ efficacy have used relatively insensitive parasitological diagnostics, such as the Kato-Katz (KK) and urine-filtration methods, thereby overestimating cure rates (CRs). This study aims to determine the efficacy of repeated PZQ treatments against Schistosoma mansoni infection in school-aged children in Côte d’Ivoire using the traditional KK technique, as well as more sensitive antigen- and DNA-detection methods.MethodsAn open-label, randomised controlled trial will be conducted in school-aged children (5 to 18 years) from the region of Taabo, Côte d’Ivoire, an area endemic for S. mansoni. This 8-week trial includes four two-weekly standard doses of PZQ in the “intense treatment” intervention group and one standard dose of PZQ in the “standard treatment” control group. The efficacy of PZQ will be evaluated in stool samples using the KK technique and real-time PCR as well as in urine using the point-of-care circulating cathodic antigen test and the up-converting phosphor, lateral flow, circulating anodic antigen assay. The primary outcome of the study will be the difference in CR of intense versus standard treatment with PZQ on individuals with a confirmed S. mansoni infection measured by KK. Secondary outcomes include the difference in CR and intensity reduction rate between the intense and standard treatment groups as measured by the other diagnostic tests, as well as the accuracy of the different diagnostic tests, and the safety of PZQ.DiscussionThis study will provide data on the efficacy of repeated PZQ treatment on the clearance of S. mansoni as measured by several diagnostic techniques. These findings will inform future mass drug administration policy and shed light on position of novel diagnostic tools to evaluate schistosomiasis control strategies.Trial registrationThe study is registered at EudraCT (2016–003017-10, date of registration: 22 July 2016) and (NCT02868385, date of registration: 16 August 2016).

437. Spatial Distribution of Schistosomiasis After Repeated Praziquantel Treatments in a Rural Community in Brazil

BackgroundSchistosomiasis is to a degree a disease of contact with fecally contaminated surface waters, rather than ingestion. Repeated treatments with praziquantel reduce schistosomiasis prevalence and morbidity; however, transmission persists and prevalence of infection often recover within a few years.MethodsIn a community in rural Bahia, Brazil that straddles a shallow river, we surveyed and treated all individuals that tested positive for schistosomiasis by Kato Katz in stools in 2009, 2012, 2013, 2015, and 2017. Upstream and downstream, as well as common water contact sites along the river were sampled and analyzed by microbial source tracking for human fecal indicator markers. The location of each home and water contact site was registered with a handheld GPS unit. Spatial analyses were performed by using QGIS software, version 2.14.ResultsThe population in the village was 460 in 2009, with minimal fluctuation over the study period. In 2009, schistosomiasis prevalence was 45%. After successive rounds of community-wide treatment with praziquantel, in the years 2012, 2013, 2015, and 2017, prevalence decreased to 24%, 16%, 13%, and 1.6%, respectively. Among the river water samples, human fecal indicator markers were detectable in minimal quantities upstream of the village. The highest concentrations were found in the downstream sections of the village. Hotspot analysis, raster calculator, and nearest neighbor analysis were used to display and analyze the prevalence of schistosomiasis. Distribution of infection was widespread initially and clustered in the downstream sections of the village after successive treatments.ConclusionIn this rural community in Brazil, sustained decrease in schistosomiasis prevalence was seen after multiple community-wide treatments over 5 years. Reinfection was not distributed randomly but concentrated in the downstream portion of the village, where human fecal water contamination is increased. Targeting sanitation in key areas may decrease sources of transmission persistence after cessation of community-wide treatment efforts.Disclosures All authors: No reported disclosures.

Association between Repeated Praziquantel treatment and Papillary, and Intrahepatic Cholangiocarcinoma

Introduction and aim. The carcinogenesis of tubular and papillary cholangiocarcinoma (CCA) differ. The available epidemiologic studies about risk factors for CCA do not differentiate between the tubular and papillary type. The current study investigated the relationship between the number of repeated use of Praziquantel (PZQ) treatments and each type of CCA.Material and methods. This was a hospital-based, matched, case-control study of patients admitted to Srinagarind Hospital, Khon Kaen University. The patients were 210 pathologically-confirmed cases of CCA, while the controls were 840 subjects diagnosed with other diseases. The 4 controls were individually matched with each case by sex, age, and date of admission. The cases were classified according to location (intrahepatic vs. extrahepatic) and cell type (papillary vs. tubular). Multivariable conditional logistic regression was used for the analysis.Results. After adjusting for confounders, there were statistically significant associations between intrahepatic and papillary CCA and repeated use of PZQ treatment. The respective odds of developing intrahepatic CCA for those who used PZQ once, twice, or more was 1.54 (95%CI:0.92-2.55 ), 2.28 (95%CI:0.91-5.73), and 4.21 (95%CI:1.61-11.05). The respective odds of developing papillary CCA for those who used PZQ once, twice, or more was 1.45 (95%CI:0.80-2.63), 2.96 (95%CI:1.06-8.24), and 3.24 (95%CI:1.09-9.66). There was no association between number of uses of PZQ treatment and developing extrahepatic or tubular CCA.Conclusion. The current study found an association between papillary and intrahepatic CCA and repeated use of PZQ treatment. We suggest further study on the risk factors for papillary and tubular CCA should be performed separately.

Repeated praziquantel treatments remodel the genetic and spatial landscape of schistosomiasis risk and transmission

Repeated treatments with praziquantel reduce schistosomiasis prevalence and morbidity, but transmission persists and populations often recover within a few years. To identify factors associated with persistence, we surveyed and treated all identified Schistosoma mansoni infections in two rural Brazilian communities (Jenipapo and Volta do Rio) in 2009, 2012 and 2013. Eggs were collected from all infected individuals and genotyped with 11 microsatellite markers to evaluate parasite differentiation and diversity. After successive rounds of community-wide treatment, prevalence decreased from 45% to 24% then 16%. Intensity of infection decreased by 57% over this period, and the number of eggs transmitted to the environment decreased by 92%. During all time periods the majority of eggs were excreted by those >15years of age. The incidence was 23% in 2012 and 15% in 2013, consistent with a decrease in transmission. There was little immigration or gene flow over a distance of 6km. On reinfection, infrapopulations were moderately differentiated indicating that pretreatment multilocus genotypes were not fully reacquired. The effective population size responded to census population decline more rapidly than differentiation. Reinfection was concentrated in the downstream portion of Jenipapo, consistent with the observed increased human fecal contamination. At this scale and in this area S. mansoni infections exist on a fragmented landscape with a highly focal pattern of transmission that may facilitate future elimination.

Association between praziquantel treatment and cholangiocarcinoma: a hospital-based matched case-control study.

BackgroundInfection by the liver fluke, Opisthorchis viverrini, remains an important public health problem in Thailand and has resulted in the highest prevalence of infection and incidence of subsequent cholangiocarcinoma (CCA) in the world. Praziquantel (PZQ) is the antihelminthic drug of choice for treatment. Previous studies in hamsters showed that repeated infection and PZQ treatment could increase the risk of CCA. However, the few available epidemiology studies in humans have shown unclear evidence of an increased risk of CCA with frequency of PZQ intake. The present study investigated the relationship between the number of repeated PZQ treatments and CCA.MethodsA hospital-based matched case–control study was conducted. All cases and controls were inpatients of a tertiary hospital in Northeast Thailand. During 2012–2014 a total of 210 incident cases of pathologically diagnosed CCA and 840 control subjects were selected from a hospital inpatient database (four controls per case). The four recruited controls were individually matched with CCA cases by gender, age and date of admission. Data were collected in face-to-face interviews using a standardised pre-tested questionnaire. Multivariable conditional logistic regression was used in the analysis of the data.ResultsThe frequencies of PZQ usage among the 210 cases and 840 controls were 48.6 vs. 66.0 for never, 32.9 vs. 24.4 for once, 8.6 vs. 4.9 for twice, and 10.0 % vs. 4.8 % for more than twice, respectively. There was a statistically significant dose–response relationship (p < 0.001). Compared with subjects who never used PZQ, those who used the medication once, twice, and more than twice were 1.49, 1.82, and 2.30 times more likely to develop CCA (95 % confidence intervals: 1.02 - 2.20, 0.92 - 3.60, and 1.20 - 4.40). These odds ratios (adjusted ORs) had already been adjusted for the effects of eating raw fish, a family history of cancer, and highest educational attainment. Additional PZQ usage increased the odds of developing CCA by 23.0 % (adjusted OR = 1.23; 95 % CI: 1.07 - 1.43).ConclusionsThe findings show that repeated PZQ treatments are associated with an increased risk of CCA. Paradoxically, this contradicts the common belief that repeated PZQ treatments decrease the risk of CCA. The study also showed a strong association between the number of repeated PZQ treatments and the consumption of raw freshwater fish. This suggests that repeated PZQ treatments may be a surrogate marker of habit of eating raw fish.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1788-6) contains supplementary material, which is available to authorized users.

Sensitivity and specificity of multiple Kato-Katz thick smears and a circulating cathodic antigen test for Schistosoma mansoni diagnosis pre- and post-repeated-praziquantel treatment.

BackgroundTwo Kato-Katz thick smears (Kato-Katzs) from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This ‘gold standard’ has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA) is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E) and drug-efficacy findings.Method/Principle FindingsIn a high S. mansoni endemic area of Uganda, three days of consecutive stool samples were collected from primary school-aged children (six - 12 years) at five time-points in year one: baseline, one-week-post-, four-weeks-post-, six-months-post-, and six-months-one-week-post-praziquantel and three time-points in years two and three: pre-, one-week-post- and four-weeks-post-praziquantel-treatment/retreatment (n = 1065). Two Kato-Katzs were performed on each stool. In parallel, one urine sample was collected and a single POC-CCA evaluated per child at each time-point in year one (n = 367). At baseline, diagnosis by two Kato-Katzs (sensitivity = 98.6%) or one POC-CCA (sensitivity = 91.7%, specificity = 75.0%) accurately predicted S. mansoni infections. However, one year later, a minimum of three Kato-Katzs, and two years later, five Kato-Katzs were required for accurate diagnosis (sensitivity >90%) and drug-efficacy evaluation. The POC-CCA was as sensitive as six Kato-Katzs four-weeks-post and six-months-post-treatment, if trace readings were classified as positive.Conclusions/SignificanceSix Kato-Katzs (two/stool from three stools) and/or one POC-CCA are required for M&E or drug-efficacy studies. Although unable to measure egg reduction rates, one POC-CCA appears to be more sensitive than six Kato-Katzs at four-weeks-post-praziquantel (drug efficacy) and six-months-post-praziquantel (M&E).

Association between Praziquantel and Cholangiocarcinoma in Patients Infected with Opisthorchis viverrini: A Systematic Review and Meta-Analysis

The liver fluke, Opisthorchis viverrini, and the associated incidence of subsequent cholangiocarcinoma (CCA) are still a public health problem in Thailand, and praziquantel (PZQ) remains the antihelminthic drug of choice for treatment. Evidence in hamsters shows that repeated infection and PZQ treatments could increase the risk of CCA. However, the existing evidence in humans is inconclusive regarding increased risk of CCA with frequency of PZQ intake. To investigate the relationship between number of repeated PZQ treatments and CCA in patients with O viverrini infection. The reviewed studies were searched in EMBASE, MEDLINE, ProQuest, PubMed and SCOPUS from inception to October, 2012 using prespecified keywords. The risk of bias (ROB) of included studies was independently assessed by two reviewers using a quality scale from the Newcastle-Ottawa Scale (NOS). Risk effect of PZQ was estimated as a pooled odds ratio (OR) with its 95% confidence interval (95%CI) in the random-effects model using DerSimonian and Laird's estimator. Three studies involving 637 patients were included. Based on the random effects model performed in two included studies of 237 patients, the association between PZQ treatments and CCA was not statistical significant with a pooled OR of 1.8 (95%CI; 0.81 to 4.16). The present systematic review and meta-analysis provides inconclusive evidence of risk effect of PZQ on increasing the risk of CCA and significant methodological limitations. Further research is urgently needed to address the shortcomings found in this review, especially the requirement for histological confirmation.

In-vivo activity of dihydroartemisinin against Schistosoma japonicum.

Schistosomiasis japonica, caused by Schistosoma japonicum, is still a major public-health concern in China, afflicting thousands of people (Zhou et al., 2007; Li et al., 2009). Since 1992, when the World Bank Loan Project for Schistosomiasis Control was initiated in China, praziquantel-based chemotherapy has been used to control the disease (Chen, 2005). Unfortunately, in the long term, repeated praziquantel treatment may lead to resistance to the drug in some Schistosoma species (Fallon et al., 1995; Ismail et al., 1996; Wang et al., 2010), and the development of new schistosomicidal drugs, as alternatives to praziquantel, is therefore a priority.

Impact of praziquantel baiting on intestinal helminths of foxes in southwestern Germany

Abstract Fox baits containing 50 mg praziquantel were distributed by aircraft in a 3000 km2 area of southwestern Germany from 1995 to 1999. 20 baits / km2 were initially distributed at intervals of six to twelve weeks. Starting from a prebaiting prevalence of 64 % (95 % C.I. 59–69), a level of 15 % (C.I. 10–21) was reached after 18 months. Further decreasing the frequency and discontinuing the bait distribution caused a surge to 55 % (C.I. 49–61) within 36 months. Other cestode species (Taenia spp., Mesocestoides spp.) showed similar responses, while the prevalence of ascarid nematodes did not decline during baiting. New infections of fox cubs with E. multilocularis, but not with other cestodes, drastically decreased after one year. Prevalences of fox helminths in an external control area remained stable. Our data suggest that repeated praziquantel treatment of free ranging foxes is suitable to reduce the prevalence of E. multilocularis in a large area.

Effects of repeated praziquantel treatment on schistosomiasis mekongi morbidity as detected by ultrasonography

Schistosomiasis mekongi is endemic in the Mekong River basin; about 80,000 people are at risk of infection in Cambodia. We conducted ultrasonographic studies of patients with schistosomiasis mekongi in Kratie province, Cambodia, focusing especially on the relationship between the frequency of praziquantel treatment and findings of ultrasonographic imaging. The frequency of praziquantel treatment in the period from 1995 to 2002 was classified into four groups: 1–2, 3–4, 5–6, and 7–8 times. Ultrasonographic images were examined to determine the presence of thickening of the portal vein wall and formation of meandering collateral circulation of the splenic vein. We selected these parameters because they are unaffected by interobserver bias. The results showed that thickening of the portal vein wall may have potential to improve with frequent praziquantel treatment. On the other hand, established hard splenomegaly and meandering collateral circulation of the splenic vein, improved very little with praziquantel treatment.

Five-year impact of repeated praziquantel treatment on subclinical morbidity due to Schistosoma japonicum in China

We report the 5-year impact (1996–2001) of repeated praziquantel chemotherapy on subclinical morbidity related to Schistosoma japonicum infection. We repeated stool examinations and hepatosplenic ultrasonography in a cohort of 120 individuals living on an island with endemic infection in Dongting Lake, China. Prevalence of schistosome infection fell by 43% and intensity (geometric mean eggs per gram) declined by 80% over the 5 years. However, transmission persisted at a dangerously high rate of 13% per year for re-infection or new infection in the cohort. The prevalence of left-lobe enlargement and dilated portal vein fell significantly ( P < 0.01) to about half initial levels although a few patients progressed during the study period. At study endpoint, infection was nearly twice as common if the portal vein was dilated (23% versus 13%, respectively), but this association was not statistically significant ( P > 0.05). However, endpoint infection was even more strongly associated with left-lobe enlargement (57% versus 15%, P < 0.01). The proportions of subjects with improved parenchymal and periportal fibrosis were much higher than the proportions of subjects that progressed ( P < 0.05). Reduction of prevalence and intensity of infection, and improvement of subclinical morbidity, were benefits of repeated treatments. Further research is needed to understand why some patients developed fibrosis despite substantial reductions in egg counts and to evaluate the functional importance of residual subclinical morbidity after chemotherapy-based control in the lake and marshland area of China.

Antibody profiles of under 6 year old children living in a Schistosoma haematobium endemic area and subjected to repeated praziquantel treatment

Antibody profiles of under 6 year old children living in a Schistosoma haematobium endemic area and subjected to repeated praziquantel treatment