SAFETY AND PHARMACOKINETICS OF PRAZIQUANTEL IN EUROPEAN POND TURTLES (EMYS ORBICULARIS).

Spirorchiidosis, caused by blood flukes of the genus Spirorchis, is a disease of great concern for the critically endangered European pond turtle (EPT; Emys orbicularis) in Switzerland. The endogenous life cycle of the parasite often leads to systemic inflammatory reactions, thrombosis, and death. Praziquantel (PZQ) is the treatment of choice against adult Spirorchis spp. in green (Chelonia mydas) and in loggerhead (Caretta caretta) sea turtles and is therefore considered for the treatment of EPT. This study aimed to establish a safe, easily applicable PZQ treatment for EPT, based on pharmacokinetics and tolerability. Three application methods were tested in a total of 12 adult EPT. Each turtle received a total of 75 mg/kg PZQ (three doses of 25 mg/kg in 3-h intervals [q3h × 3]) via IM (n = 3 turtles), SC (n = 3 turtles), or PO (n = 6 turtles) administration. Blood was collected 3, 6, 24, and 48 h after the first administration to determine the plasma concentration of PZQ using high-performance liquid chromatography coupled to mass spectrometry. Maximum measured R-PZQ concentrations (Cmax) were reached after 6 h. The mean Cmax of the total PZQ (sum of R- and S-PZQ) in the PO-treated EPT group was 1,929 ng/ml. Significantly higher concentrations were measured after IM and SC injection (mean Cmax of total PZQ = 12,715 ng/ml and 10,114 ng/ml, respectively). Transient side effects were evident after IM administration (local swelling and lameness), whereas no adverse drug effects were observed after PO and SC administration. Based on these results and the ease of administration to EPT, SC injection of PZQ at 25 mg/kg q3h times 3 serves as promising treatment application for the future.

Feasibility and safety of integrating mass drug administration for helminth control with seasonal malaria chemoprevention among Senegalese children: a randomized controlled, observer-blind trial.

BACKGROUND: The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that may help to achieve elimination of malaria and helminths. A randomized, controlled, observer-blind trial was conducted to assess the feasibility and safety of combining mass drug administration (MDA) for schistosomiasis and soil transmitted helminths (STH) with seasonal malaria chemoprevention (SMC) among children living in Senegal. METHODS: Female and male children aged 1-14 years were randomized 1:1:1, to receive Vitamin A and Zinc on Day 0, followed by SMC drugs (sulfadoxine-pyrimethamine and amodiaquine) on Days 1-3 (control group); or praziquantel and Vitamin A on Day 0, followed by SMC drugs on Days 1-3 (treatment group 1); or albendazole and praziquantel on Day 0, followed by SMC drugs on Days 1-3 (treatment group 2). Safety assessment was performed by collecting adverse events from all children for six subsequent days following administration of the study drugs. Pre- and post-intervention, blood samples were collected for determination of haemoglobin concentration, malaria microscopy, and PCR assays. Stool samples were analyzed using Kato-Katz, Merthiolate-iodine-formalin and PCR methods. Urine filtration, PCR and circulating cathodic antigen tests were also performed. RESULTS: From 9 to 22 June 2022, 627 children aged 1-14 years were randomized into the three groups described above. Mild, transient vomiting was observed in 12.6% (26/206) of children in treatment group 2, in 10.6% (22/207) in group 1, and in 4.2% (9/214) in the control group (p = 0.005). Pre-intervention, the geometric mean value of Plasmodium falciparum parasite density was highest among children who received albendazole, praziquantel with SMC drugs. Post-intervention, the parasite density was highest among children who received SMC drugs only. Children who received praziquantel and SMC drugs had a lower risk of developing severe anaemia than their counterparts who received SMC drugs alone (OR = 0.81, 95% CI 0.13-5.00, p = 0.63). CONCLUSIONS: Integration of MDA for helminths with SMC drugs was safe and feasible among Senegalese children. These findings support further evaluation of the integrated control model. TRIAL REGISTRATION: The study is registered at Clinical Trial.gov NCT05354258.

Efficacy and safety of antiparasitic therapy for neurocysticercosis in rural Tanzania: a prospective cohort study.

PURPOSE: Neurocysticercosis is common in regions endemic for Taenia solium. Active-stage neurocysticercosis can be treated with antiparasitic medication, but so far no study on efficacy and safety has been conducted in Africa. METHODS: We conducted a prospective cohort study on treatment of neurocysticercosis in Tanzania between August 2018 and January 2022. Patients were initially treated with albendazole (15 mg/kg/d) for 10 days and followed up for 6 months. Additionally in July 2021, all participants who then still had cysts were offered a combination therapy consisting of albendazole (15 mg/kg/d) and praziquantel (50 mg/kg/d). Antiparasitic treatment was accompanied by corticosteroid medication and anti-seizure medication if the patient had experienced epileptic seizures before treatment. RESULTS: Sixty-three patients were recruited for this study, of whom 17 had a complete follow-up after albendazole monotherapy. These patients had a total of 138 cysts at baseline, of which 58 (42%) had disappeared or calcified by the end of follow-up. The median cyst reduction was 40% (interquartile range 11-63%). Frequency of epileptic seizures reduced considerably (p < 0.001). Three patients had all active cysts resolved or calcified and of the remaining 14, eight received the combination therapy which resolved 63 of 66 cysts (95%). Adverse events were infrequent and mild to moderate during both treatment cycles. CONCLUSION: Cyst resolution was unsatisfactory with albendazole monotherapy but was very high when it was followed by a combination of albendazole and praziquantel.

Treatment of primate platynosomosis: A word of caution about the use of praziquantel in marmosets.

BACKGROUND: The successive reports of Platynosomum illiciens in Neotropical captive primates have increased interest in platynosomosis; however, its treatment is little known. METHODS: Callithrix penicillata (n = 10) naturally and chronically infected with P. illiciens were treated with praziquantel (25 mg/kg BW, three s.c. doses at 24 hours intervals), and coproparasitological tests performed over 67 days. The proportions of primates with a reduction in fecal egg counts (FEC) or negative results progressively increased after treatment, and at the last fecal tests, marmosets were negative. RESULTS AND CONCLUSIONS: Although all primates tolerated the initial days of study well, 40% (4/10) of them died between the 8th and 16th days after the onset of treatment. Clinical signs and necropsies indicated the occurrence of hepatic involvement, biliary obstruction, and cholangitis. Marmosets with a higher previous FEC were more likely to die after treatment. Use of praziquantel should be considered carefully on a case-by-case basis.

Anthelmintics for people with neurocysticercosis.

BACKGROUND: Neurocysticercosis is a parasitic infection of the central nervous system by the larval stage of the pork tapeworm and is a common cause of seizures and epilepsy in endemic areas. Anthelmintics (albendazole or praziquantel) may be given alongside supportive treatment (antiepileptics/analgesia) with the aim of killing these larvae (cysticerci), with or without corticosteroid treatment. However, there are potential adverse effects of these drugs, and the cysticerci may eventually die without directed anthelminthic treatment. OBJECTIVES: To assess the effects of anthelmintics on people with neurocysticercosis. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, the WHO ICTRP, and ClinicalTrials.gov, up to 21 October 2020. SELECTION CRITERIA: Randomized controlled trials comparing anthelmintics and supportive treatment (+/- corticosteroids) with supportive treatment alone (+/- corticosteroids) for people with neurocysticercosis. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the title and abstract of all articles identified by the search. We obtained full-text articles to confirm the eligibility of all studies that passed screening. One review author extracted data, which a second review author checked. Two review authors assessed the risk of bias of each trial and performed GRADE assessments. In cases of disagreement at consensus discussion stage between review authors, we consulted a third review author. We calculated risk ratios (RR) for dichotomous variables, with 95% confidence intervals (CIs) for pooled data from studies with similar interventions and outcomes. MAIN RESULTS: We included 16 studies in the review. Only two studies investigated praziquantel and did not report data in a format that could contribute to meta-analysis. Most results in this review are therefore applicable to albendazole versus placebo or no anthelmintic. The aggregate analysis across all participants with neurocysticercosis did not demonstrate a difference between groups in seizure recurrence, but heterogeneity was marked (RR 0.94, 95% CI 0.78 to 1.14; 10 trials, 1054 participants; I2 = 67%; low-certainty evidence). When stratified by participants with a single cyst or multiple cysts, pooled analysis suggests that albendazole probably improves seizure recurrence for participants with a single cyst (RR 0.61, 95% CI 0.4 to 0.91; 5 trials, 396 participants; moderate-certainty evidence). All studies contributing to this analysis recruited participants with non-viable, intraparenchymal cysts only, and most participants were children. We are uncertain whether or not albendazole reduces seizure recurrence in participants with multiple cysts, as the certainty of the evidence is very low, although the direction of effect is towards albendazole causing harm (RR 2.05, 95% CI 1.28 to 3.31; 2 trials, 321 participants; very low-certainty evidence). This analysis included a large study containing a highly heterogeneous population that received an assessment of unclear risk for multiple 'Risk of bias' domains. Regarding radiological outcomes, albendazole probably slightly improves the complete radiological clearance of lesions (RR 1.22, 95% CI 1.07 to 1.39; 13 trials, 1324 participants; moderate-certainty evidence) and the evolution of cysts (RR 1.27, 95% CI 1.10 to 1.47; 6 trials, 434 participants; moderate-certainty evidence). More adverse events appeared to be observed in participants treated with either albendazole or praziquantel compared to those receiving placebo or no anthelmintic. The most commonly reported side effects were headache, abdominal pain, and nausea/vomiting. AUTHORS' CONCLUSIONS: For participants with a single cyst, there was less seizure recurrence in the albendazole group compared to the placebo/no anthelmintic group. The studies contributing to this evidence only recruited participants with a non-viable intraparenchymal cyst. We are uncertain whether albendazole reduces seizure recurrence for participants with multiple cysts. We also found that albendazole probably increases radiological clearance and evolution of lesions. There were very few studies reporting praziquantel outcomes, and these findings apply to albendazole only.

Acute pancytopenia due to praziquantel treatment for cerebral cysticercosis: A rare case report.

Praziquantel (PZQ) has been commonly used to treat diverse parasitic infections for over thirty years. Many studies have confirmed its efficacy for the treatment of cysticercosis and the side effects. We reported a rare case of a 56-year-old Chinese man with cerebral cysticercosis. He had experienced acute pancytopenia two times following PZQ treatment (40 mg/kg per day for five days) and gradually recovered after PZQ withdrawal, which was an adverse effect of PZQ that was not previously reported in the literatures. It is suggested that medical observation and dynamic monitoring of PBC should be maintained throughout the entire PZQ therapy course until two weeks after the drug withdrawal, especially in elderly people and those receiving increasing dosages.

Maternal anemia type during pregnancy is associated with anemia risk among offspring during infancy.

BACKGROUND: We evaluated the association between etiology of maternal anemia and iron status throughout infancy. METHODS: Samples from a study designed to examine Praziquantel treatment during pregnancy were used (n = 359). All women were infected with schistosomiasis and randomized to Praziquantel or placebo at 16 ± 2 weeks' gestation. Hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin, C-reactive protein, and interleukin-6 were measured in maternal and infant blood. The relationship between both maternal Praziquantel treatment and etiology of anemia and infant iron status was evaluated. RESULTS: Maternal iron-deficiency anemia was associated with increased risk of infant anemia at 6 months of age. Infants of mothers with the lowest levels of circulating hepcidin during gestation, likely a marker for iron deficiency, had higher sTfR:SF levels and lower hemoglobin levels, particularly at 12 months of age. Maternal non-iron-deficiency anemia (NIDA) did not impact infant anemia risk or iron status. Maternal treatment for schistosomiasis had no effect on infant hematologic status. CONCLUSIONS: Maternal iron deficiency anemia was associated with an increased risk for anemia or iron deficiency during late infancy. We did not observe an association between maternal NIDA and increased risk for iron deficiency during infancy.

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.

Efficacy and Safety of Praziquantel Against Light Infections of Opisthorchis viverrini: A Randomized Parallel Single-Blind Dose-Ranging Trial.

Background: The liver fluke Opisthorchis viverrini, highly prevalent in Southeast Asia, is an important public health burden, including a risk factor for developing an aggressive bile duct cancer, cholangiocarcinoma, in chronically infected patients. Praziquantel, administered at a single 40 mg/kg dose in preventive chemotherapy programs and 3 × 25 mg/kg for individual treatment, is the drug of choice, yet information on the nature of the dose-response relationship is lacking. Methods: We performed a randomized, parallel, single-blind dose-ranging phase 2 trial in the Lao People's Democratic Republic in O. viverrini­infected adults. Patients were randomly assigned to 30 mg/kg, 40 mg/kg, 50 mg/kg, or 3 × 25 mg/kg praziquantel or placebo. Adverse events were recorded at baseline, 3 hours, and 24 hours posttreatment. Cure rates (CRs) and egg reduction rates (ERRs) were estimated 3 weeks after drug administration using available case analysis. Dose-response curves were predicted using Emax models. Results: Two-hundred seventeen O. viverrini­infected patients were assigned to the 5 treatment arms. The majority (94.3%) of patients harbored light infections. The Emax model predicted a high efficacy among the observed dose range. We observed CRs ranging from 92.7% to 95.5% and ERRs >99.5% for all praziquantel treatment groups. Adverse events were mild but higher in the standard treatment group (3 × 25 mg/kg) than in the single-dose treatment arms. Conclusions: Single-dose praziquantel appears to be as efficacious as the standard 3 × 25 mg/kg regimen for the treatment of O. viverrini infections, while presenting fewer adverse events. Further studies are necessary in moderate and heavy O. viverrini infections. Clinical Trials Registration: Randomized Controlled Trials (ISRCTN77186750).

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

BACKGROUND: Infection 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. METHODS: A 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. RESULTS: The 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). CONCLUSIONS: The 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.

Reduced uptake of mass treatment for schistosomiasis control in absence of food: beyond a randomized trial.

BACKGROUND: Sustaining high uptake of praziquantel is key for long-term control of schistosomiasis. During mass treatment in 2013, we randomized 12 primary schools into two groups; one group received education messages for schistosomiasis prevention for two months prior to mass treatment, while the other, in addition to the education messages, received a pre-treatment snack shortly before mass treatment. The uptake of praziquantel in the snack schools was 94 % compared to 79 % in the non-snack schools. During mass treatment in 2014, no snack was provided. We compared the uptake of praziquantel in 2014 to that in 2013 and attempt to explain the reasons for the observed differences. METHODS: Serial cross sectional surveys were conducted among a random sample of children from the 12 primary schools, 1 month after mass treatment in 2013 and 2014 to measure uptake of praziquantel, reported side effects attributable to praziquantel and prevalence and intensity of schistosomiasis infection. Differences in the demographic and descriptive variables between the 2013 and 2014 samples were compared using chi squared tests for categorical variables and student's t-test for geometric mean intensity of S. mansoni infection. RESULTS: Uptake of praziquantel reduced from 93.9 to 78.0 % (p = 0.002) in the snack schools but was unchanged in the non-schools 78.7 and 70.4 % (p = 0.176). The occurence of side-effects attributable to praziquantel increased from 34.4 to 61.2 % (p = 0.001) in the snack schools but was unchanged in the non-snack schools; 46.9 and 53.2 % (p = 0.443). Although the prevalence of S. mansoni infection increased in both the snack and non-snack schools, the differences did not reach statistical significance;1.3 and 7.5 % (p = 0.051) and 14.1 and 22.0 % (p = 0.141), respectively. Similarly, the difference in the geometric mean intensity of S. mansoni infection in both the snack and non-snack schools was not statistically significant; 38.3 eggs per gram of stool (epg) and 145.7 epg (p = 0.197) and 78.4 epg and 322.5 epg (p = 0.120), respectively. CONCLUSION: Our results show that in absence of food, uptake of praziquantel reduced and the side-effects of the drug increased. However, the reduced uptake did not affect the prevalence and intensity of schistosomiasis among school children. Rescinding of the provision of the snack is what probably caused the reduction in uptake of treatment in the subsequent mass treatment cycle.

Identification of a nonsense mutation in feline ABCB1.

The aim of this study was to sequence all exons of the ABCB1 (MDR1) gene in cats that had experienced adverse reactions to P-glycoprotein substrate drugs (phenotyped cats). Eight phenotyped cats were included in the study consisting of eight cats that experienced central nervous system toxicosis after receiving ivermectin (n = 2), a combination product containing moxidectin and imidacloprid (n = 3), a combination product containing praziquantel and emodepside (n = 1) or selamectin (n = 2), and 1 cat that received the product containing praziquantel and emodepside but did not experience toxicity (n = 1). Fifteen exons contained polymorphisms and twelve exons showed no variation from the reference sequence. The most significant finding was a nonsense mutation (ABCB11930_1931del TC) in one of the ivermectin-treated cats. This cat was homozygous for the deletion mutation. All of the other phenotyped cats were homozygous for the wild-type allele. However, 14 missense mutations were identified in one or more phenotyped cats. ABCB11930_1931del TC was also identified in four nonphenotyped cats (one homozygous and three heterozygous for the mutant allele). Cats affected by ABCB11930_1931del TC would be expected to have a similar phenotype as dogs with the previously characterized ABCB1-1Δ mutation.

Topical praziquantel as a new treatment for perioral dermatitis: results of a randomized vehicle-controlled pilot study.

BACKGROUND: Perioral dermatitis (POD) is a common skin disease, and extending the range of treatments available for this condition is important. AIM: To evaluate the safety, efficacy and tolerability of praziquantel 3% ointment as monotherapy. METHODS: This was a single-centre, randomized, single-blind, vehicle-controlled pilot study in adult patients (n = 46) with 4 weeks of treatment and 4 weeks of follow-up. Efficacy was assessed clinically using the Investigator's Global Assessment (IGA) and the Perioral Dermatitis Severity Index (PODSI). Quality of life (QOL) was determined by the Dermatology Quality of Life Index (DLQI). RESULTS: PODSI was significantly lower in the praziquantel group than in the placebo (vehicle) group, both during treatment and period. Mean IGA score showed a statistically significant therapeutic advantage of praziquantel over placebo at week 4 (P < 0.001). The praziquantel group experienced a greater improvement in mean DLQI. No serious treatment-related adverse events occurred in either group. CONCLUSIONS: Praziquantel ointment 3% effectively improves POD symptoms and QOL.

Antimalarial artesunate-mefloquine versus praziquantel in African children with schistosomiasis: an open-label, randomized controlled trial.

Schistosomiasis treatment entirely relies on a single drug, praziquantel, prompting research into alternative therapeutics. Here we evaluated the efficacy and safety of the antimalarial combination artesunate-mefloquine for the treatment of schistosomiasis in a proof-of-concept, pragmatic, open-label, randomized controlled trial in primary schools of six villages endemic for schistosomiasis in northern Senegal. Children (6-14 years) were eligible if Schistosoma eggs were detected by microscopy in urine and/or stool. In total, 726 children were randomized 1:1 to praziquantel (standard care: 40 mg kg-1 single dose; n = 364) or to artesunate-mefloquine (antimalarial dosage: artesunate 4 mg kg-1 and mefloquine 8 mg kg-1 daily for three consecutive days; n = 362). Eight children not meeting the inclusion criteria were excluded from efficacy analysis. Median age of the remaining 718 participants was 9 years; 399 (55.6%) were male, and 319 (44.4%) female; 99.3% were infected with Schistosoma haematobium and 15.2% with S. mansoni. Primary outcomes were cure rate, assessed by microscopy, and frequency of drug-related adverse effects of artesunate-mefloquine versus praziquantel at 4 weeks after treatment. Cure rate was 59.6% (208/349) in the artesunate-mefloquine arm versus 62.1% (211/340) in the praziquantel arm. The difference of -2.5% (95% confidence interval (CI) -9.8 to 4.8) met the predefined criteria of noninferiority (margin set at 10%). All drug-related adverse events were mild or moderate, and reported in 28/361 children receiving artesunate-mefloquine (7.8%; 95% CI 5.4 to 11.0) versus 8/363 (2.2%; 95% CI 1.1 to 4.3) receiving praziquantel (P < 0.001). Artesunate-mefloquine at antimalarial dosage was moderately safe and noninferior to standard-care praziquantel for the treatment of schistosomiasis, predominantly due to S. haematobium. Multicentric trials in different populations and epidemiological settings are needed to confirm these findings. ClinicalTrials.gov identifier: NCT03893097 .

Efficacy of a Single Oral Dose of Artesunate plus Sulfalene-Pyrimethamineversus Praziquantel in the Treatment of Schistosoma mansoni in Kenyan Children: An Open-Label, Randomized, Exploratory Trial.

Unlike praziquantel, artemisinin derivatives are effective against juvenile schistosome worms. We assessed the efficacy and safety of a single oral dose of artesunate plus sulfalene-pyrimethamine versus praziquantel in the treatment of Schistosoma mansoni. Seventy-three schoolchildren (aged 9-15 years) with confirmed S. mansoni infection in Rarieda, western Kenya, were randomly assigned to receive either a single oral dose of artesunate plus sulfalene-pyrimethamine (n = 39) or a single dose of praziquantel (n = 34). The cure and egg reduction rates at 4 weeks posttreatment were 69.4% (25/36) versus 80.6% (25/31) (P = 0.297) and 99.1% versus 97.5% (P = 0.607) in the artesunate plus sulfalene-pyrimethamine group versus praziquantel group, respectively. Fourteen children developed adverse events, and there were no serious adverse events. A single oral dose of artesunate plus sulfalene-pyrimethamine has efficacy comparable to that of praziquantel in the treatment of S. mansoni, but these results should be confirmed in larger randomized controlled trials.

Praziquantel-related visual disorders among recipients in mass drug administration campaigns in schistosomiasis endemic settings: Systematic review and meta-analysis protocol.

BACKGROUND: Hundreds of millions of doses of Praziquantel (PZQ) have been administered to persons with and without schistosomiasis living in schistosomiasis endemic settings, through the mass drug administration (MDA) strategy which started in the early 2000s. A recent publication suggested high risk of PZQ-related visual disorders, raising public health concerns. We aim to systematically synthesize evidence on the magnitude of PZQ-related visual disorders. METHODS: We will search PubMed, Google Scholar, CINAHL, SCOPUS, CENTRAL and LILACS from 1977 (when the first human clinical trials on PZQ started) to 31st May 2024, with no language restrictions. The key search terms will include "Praziquantel", "PZQ", "visual disorder", "adverse events", "side effects", "blurry vision" and "visual impairment" together with alternative terms and synonyms. All the countries endemic for schistosomiasis will be included as search terms. We will also search HINARI, Africa Journals Online, Thesis Databases and Preprint Repositories. Where necessary, we will contact expert researchers working in the field of schistosomiasis, UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), pharmaceutical industries, country-specific Food and Drug Authorities (FDAs) and the European Medicines Agency databases. We will search Conference Proceedings and reference lists of relevant studies for additional studies. At least two authors will independently select studies, extract data and assess risk of bias in the included studies. Any disagreements or discrepancies will be resolved through discussion between the reviewers. Heterogeneity will be explored graphically, and statistically using the I2-statistic. We will conduct random-effects meta-analysis when heterogeneity is appreciable, and express dichotomous outcomes (visual adverse events including excessive lacrimation, blurry vision and visual impairments) as risk ratio (RR) or Odds Ratio (OR) with their 95% confidence interval (CI). We will perform subgroup analysis to assess the impact of heterogeneity, and sensitivity analyses to test the robustness of the effect estimates. The overall level of evidence will be assessed using GRADE. EXPECTED OUTCOMES: The present review expects to identify and categorize visual disorders occurring after administration of PZQ, alone or in combination with other drugs. By synthesizing the data from multiple studies, the review aims to present a quantitative assessment of the risk or odds of experiencing a visual disorder in different populations after ingesting PZQ. The review will also generate insights into whether PZQ in combination with other drugs are associated with increased odds of visual disorders and whether the occurrence of visual disorders correlates with dosage or treatment duration. Policymakers, public health experts and stakeholders could rely on the review findings to deliver context-sensitive preventive chemotherapy programs by adjusting drug combinations or dosing schedules to reduce risk of visual adverse effects in populations treated with PZQ. The review aims to identify gaps in the current evidence regarding visual disorders following PZQ administration in schistosomiasis endemic settings which can serve as the basis for future research on important but unanswered questions. DISSEMINATION AND PROTOCOL REGISTRATION: The findings of this study will be disseminated through stakeholder forums, conferences, and peer-review publications. The review protocol has been registered in the International Prospective Register for Systematic Reviews (PROSPERO)- CRD42023417963.

Efficacy and safety of single-dose artesunate plus sulfalene/pyrimethamine combined with praziquantel for the treatment of children with Schistosoma mansoni or Schistosoma haematobium in western Kenya: a randomised, open-label controlled trial.

BACKGROUND: Reliance on praziquantel for the treatment and control of schistosomiasis is likely to facilitate the emergence of drug resistance. Combination therapy targeting adult and juvenile schistosome worms is urgently needed to improve praziquantel efficacy and delay the potential development of drug resistance. We assessed the efficacy and safety of single-dose praziquantel combined with single-dose artesunate plus sulfalene-pyrimethamine in the treatment of Kenyan children with schistosomiasis. METHODS: This was an open-label, randomised clinical trial involving 426 school-aged children (7-15 years old) diagnosed with Schistosoma mansoni (by Kato-Katz) or S. haematobium (by urine filtration). They were randomly assigned (1:1:1) to receive a single dose of praziquantel (40 mg/kg), a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate) or combination therapy using a single dose of praziquantel (40 mg/kg) combined with a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate). The primary outcome was cure and egg reduction rates at 6 weeks post-treatment in the available case population. Adverse events were assessed within 3 h after treatment. RESULTS: Of the 426 children enrolled, 135 received praziquantel, 150 received artesunate plus sulfalene-pyrimethamine, and 141 received combination therapy. Outcome data were available for 348 (81.7%) children. For S. mansoni-infected children (n = 335), the cure rates were 75.6%, 60.7%, and 77.8%, and the egg reduction rates were 80.1%, 85.0%, and 88.4% for praziquantel, artesunate plus sulfalene-pyrimethamine, and combination therapy, respectively. For S. haematobium-infected children (n = 145), the corresponding cure rates were 81.4%, 71.1%, and 82.2%, and the egg reduction rates were 95.6%, 97.1%, and 97.7%, respectively. Seventy-one (16.7%) children reported mild-intensity adverse events. The drugs were well tolerated and no serious adverse events were reported. CONCLUSIONS: A single oral dose of praziquantel combined with artesunate plus sulfalene-pyrimethamine cured a high proportion of children with S. haematobium but did not significantly improve the treatment efficacy for either urinary or intestinal schistosomiasis. Sequential administration of praziquantel and artesunate plus sulfalene-pyrimethamine may enhance the efficacy and safety outcomes.

Efficacy and safety of tribendimidine against Clonorchis sinensis.

BACKGROUND: Clonorchiasis is of considerable public health importance, particularly in the People's Republic of China (PR China), where most of the 15 million individuals infected with Clonorchis sinensis are currently concentrated. Praziquantel is the drug of choice, but tribendimidine might be an alternative. METHODS: We performed a randomized open-label trial in Guangxi, PR China, to assess the efficacy and safety of 400 mg tribendimidine once, 400 mg tribendimidine daily for 3 days, and 75 mg/kg praziquantel in 1 day divided in 3 doses against parasitological-confirmed C. sinensis infections. Cure and egg reduction rates were determined 3 weeks posttreatment using available case analysis. Clinical symptoms were documented at baseline, and adverse events were recorded and graded 3 and 24 hours after each dose. RESULTS: A total of 74 patients were included in the final analysis. Single-dose tribendimidine achieved a cure rate of 44%, whereas cure rates of 58% and 56% were obtained for tribendimidine administered for 3 days and praziquantel, respectively. High egg reduction rates (97.6%-98.8%) were observed for all treatment regimens. Single-dose tribendimidine was the best-tolerated treatment scheme. Patients treated with praziquantel experienced significantly more adverse events than did tribendimidine recipients (P < .05). CONCLUSIONS: Tribendimidine has an efficacy comparable to praziquantel in the treatment of C. sinensis infection and resulted in fewer adverse events compared to praziquantel. Larger clinical trials are warranted among C. sinensis-infected patients to determine the potential of tribendimidine against clonorchiasis and other helminthiases. Clinical Trials Registration.Controlled-Trials.com, ISRCTN80829842.

Efficacy and side effects of praziquantel in the treatment for Schistosoma mansoni infection in school children in Senbete Town, northeastern Ethiopia.

OBJECTIVE: To assess the efficacy and side effects of praziquantel in the treatment for Schistosoma mansoni infection in school children in Senbete Town, northeastern Ethiopia. METHODS: A single stool specimen was collected from 342 school children and examined for S. mansoni ova using Kato-Katz technique (single slide) and formol-ether concentration technique. Positive individuals were treated with a single oral dose of praziquantel at 40 mg/kg body weight. Egg reduction and cure rates were assessed 4 weeks post-treatment. Structured questionnaires were also used to collect pre-treatment and 24-h post-treatment signs and symptoms to assess side effects of the drug. RESULTS: Praziquantel reduced the egg rate by 79.46% and achieved a cure rate of 82.89% 4 weeks post-treatment. 86.67% of the children presented at least one transient drug-related sign and symptom 24-h post-treatment. CONCLUSION: Praziquantel demonstrated sufficient efficacy against S. mansoni in Senbete Town, northeastern Ethiopia. Mild and transient signs and symptoms associated with therapy disappeared within 24 h without specific treatment.

Detectable urogenital schistosome DNA and cervical abnormalities 6 months after single-dose praziquantel in women with Schistosoma haematobium infection.

We explored response to single-dose praziquantel therapy in a cohort of 33 women with Schistosoma haematobium infection in rural Mwanza, Tanzania. Women with S. haematobium infection confirmed both by eggs in urine and by polymerase chain reaction (PCR) received single-dose praziquantel and treatment of concomitant sexually transmitted infections. Macroscopic cervical abnormalities were also quantified. After 6 months, microscopically detectable egg excretion was eliminated, but 8 of 33 women (24%) were persistently positive for S. haematobium by PCR, and 11 (33%) had cervical abnormalities potentially attributable to schistosomiasis. This suggests that praziquantel treatment more frequently than every 6 months may be necessary for complete elimination of the parasite and prevention of genital tissue pathology. This aggressive therapy may in turn play a key role decreasing HIV susceptibility in millions of people living in regions in which S. haematobium is endemic.