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Nature Medicine Jan 2024Schistosomiasis treatment entirely relies on a single drug, praziquantel, prompting research into alternative therapeutics. Here we evaluated the efficacy and safety of... (Randomized Controlled Trial)
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 single dose; n = 364) or to artesunate-mefloquine (antimalarial dosage: artesunate 4 mg kg and mefloquine 8 mg kg 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 .
Topics: Child; Female; Humans; Male; Antimalarials; Artesunate; Mefloquine; Praziquantel; Schistosomiasis; Treatment Outcome; Adolescent
PubMed: 38177851
DOI: 10.1038/s41591-023-02719-4 -
BMC Research Notes Oct 2023Galectins are sugar-binding proteins that participate in many biological processes, such as immunity, by regulating host immune cells and their direct interaction with...
OBJECTIVE
Galectins are sugar-binding proteins that participate in many biological processes, such as immunity, by regulating host immune cells and their direct interaction with pathogens. They are involved in mediating infection by Schistosoma mansoni, a parasitic trematode that causes schistosomiasis. However, their direct effects on schistosomes have not been investigated.
RESULTS
We found that galectin-2 recognizes S. mansoni glycoconjugates and investigated whether galectin-1, 2, and 3 can directly affect S. mansoni in vitro. Adult S. mansoni were treated with recombinant galectin-1, 2, and 3 proteins or praziquantel, a positive control. Treatment with galectin-1, 2, and 3 had no significant effect on S. mansoni motility, and no other differences were observed under a stereoscopic microscope. Hence, galectin-1, 2, and 3 may have a little direct effect on S. mansoni. However, they might play a role in the infection in vivo via the modulation of the host immune response or secretory molecules from S. mansoni. To the best of our knowledge, this is the first study to investigate the direct effect of galectins on S. mansoni and helps in understanding the roles of galectins in S. mansoni infection in vivo.
Topics: Animals; Galectin 1; Galectins; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni
PubMed: 37817269
DOI: 10.1186/s13104-023-06530-9 -
Infection Aug 2023Neurocysticercosis is common in regions endemic for Taenia solium. Active-stage neurocysticercosis can be treated with antiparasitic medication, but so far no study on...
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.
Topics: Humans; Neurocysticercosis; Albendazole; Antiparasitic Agents; Praziquantel; Tanzania; Prospective Studies; Cysts; Seizures; Anthelmintics
PubMed: 36961623
DOI: 10.1007/s15010-023-02021-y -
Immunotherapy Advances 2023Control of schistosomiasis depends on a single drug, praziquantel, with variable cure rates, high reinfection rates, and risk of drug resistance. A vaccine could...
Control of schistosomiasis depends on a single drug, praziquantel, with variable cure rates, high reinfection rates, and risk of drug resistance. A vaccine could transform schistosomiasis control. Preclinical data show that vaccine development is possible, but conventional vaccine efficacy trials require high incidence, long-term follow-up, and large sample size. Controlled human infection studies (CHI) can provide early efficacy data, allowing the selection of optimal candidates for further trials. A CHI has been established in the Netherlands but responses to infection and vaccines differ in target populations in endemic countries. We aim to develop a CHI for in Uganda to test candidate vaccines in an endemic setting. This is an open-label, dose-escalation trial in two populations: minimal, or intense, prior exposure. In each population, participants will be enrolled in sequential dose-escalating groups. Initially, three volunteers will be exposed to 10 cercariae. If all show infection, seven more will be exposed to the same dose. If not, three volunteers in subsequent groups will be exposed to higher doses (20 or 30 cercariae) following the same algorithm, until all 10 volunteers receiving a particular dose become infected, at which point the study will be stopped for that population. Volunteers will be followed weekly after infection until CAA positivity or to 12 weeks. Once positive, they will be treated with praziquantel and followed for one year. The trial registry number is ISRCTN14033813 and all approvals have been obtained. The trial will be subjected to monitoring, inspection, and/or audits.
PubMed: 37538934
DOI: 10.1093/immadv/ltad010 -
Revista Espanola de Enfermedades... Nov 2023Schistosomiasis is a parasitic infection caused by trematode species of the genus Schistosoma. It is prevalent in tropical regions of Africa, Asia and South America,...
Schistosomiasis is a parasitic infection caused by trematode species of the genus Schistosoma. It is prevalent in tropical regions of Africa, Asia and South America, being rare in Europe, where it is usually diagnosed in immigrants and tourists from endemic areas. It has different clinical forms of presentation. Hepatosplenic schistosomiasis produces periportal fibrosis, which can progress to presinusoidal portal hypertension, with all its associated complications. We present the case of a 43-year-old female patient from the Philippines who was referred to gastroenterology consultation due to liver enzyme alteration with a predominantly cholestatic pattern. An aetiological study was performed, with negative results. An abdominal ultrasound revealed signs of chronic liver disease, with transient elastography of 9.5 kPa. A percutaneous liver biopsy was performed, with histological findings consistent with infestation by schistosome eggs, receiving treatment with praziquantel and subsequently verifying its eradication with a stool test.
PubMed: 37982557
DOI: 10.17235/reed.2023.10036/2023 -
Trials Nov 2023Schistosomiasis control relies on praziquantel for preventive chemotherapy. Alternative drugs are needed for the treatment and control of schistosomiasis. Praziquantel...
SCHISTOACT: a protocol for an open-label, five-arm, non-inferiority, individually randomized controlled trial of the efficacy and safety of praziquantel plus artemisinin-based combinations in the treatment of Schistosoma mansoni infection.
BACKGROUND
Schistosomiasis control relies on praziquantel for preventive chemotherapy. Alternative drugs are needed for the treatment and control of schistosomiasis. Praziquantel is effective against adult schistosome worms but ineffective against larval stages of the parasite and cannot prevent re-infection or interrupt the transmission of infection. Continued reliance on praziquantel for wide-scale schistosomiasis control will likely accelerate the emergence of drug resistance. Artemisinin derivatives are effective against the juvenile stages but ineffective against adult worms. The SCHISTOACT study aimed to evaluate the efficacy and safety of praziquantel plus one of four artemisinin-based combinations in treating Schistosoma mansoni infection in Kenya.
METHODS
The SCHISTOACT study is an open-label, head-to-head, five-arm, proof-of-concept, non-inferiority, individually randomized controlled trial with a follow-up of 12 weeks. A total of 540 primary school-aged children from the Mwea area, Kirinyaga County in central Kenya, diagnosed with S. mansoni infection (by Kato-Katz method) are randomly allocated (1:1:1:1:1) to a single dose of praziquantel plus a 3-day course of artesunate-sulfalene/pyrimethamine, or artesunate-amodiaquine, or artesunate plus mefloquine, or dihydroartemisinin-piperaquine, or praziquantel control arm. The primary endpoints are efficacy (cure rate, assessed by microscopy) and safety (adverse events) of each study arm 6 weeks after treatment. Secondary endpoints include cumulative cure rate, egg reduction rate, and re-infection 12 weeks after treatment. The non-inferiority margin is set at - 10 for the risk difference in cure rates between praziquantel and the combined treatment.
DISCUSSION
This study assesses a strategy for repurposing artemisinin-based combination therapies (ACTs) for treating schistosomiasis. It adopts a head-to-head comparison of four different ACTs to test a non-inferiority hypothesis and to strengthen local capacity to conduct clinical trials for interventions against neglected tropical diseases.
TRIAL REGISTRATION
Pan-African Clinical Trials Registry PACTR202001919442161 . Retrospectively registered on 6 January 2020.
Topics: Adult; Animals; Child; Humans; Anthelmintics; Artemisinins; Artesunate; Drug Therapy, Combination; Praziquantel; Randomized Controlled Trials as Topic; Reinfection; Schistosoma mansoni; Schistosomiasis; Schistosomiasis mansoni; Treatment Outcome; Equivalence Trials as Topic
PubMed: 38012787
DOI: 10.1186/s13063-023-07790-3 -
Crystal Growth & Design Jun 2024New cocrystals of praziquantel with suberic, 3-hydroxybenzoic, benzene-1,2,4,5-tetracarboxylic, trimesic, and 5-hydroxyisophthalic acids were obtained through ball...
New cocrystals of praziquantel with suberic, 3-hydroxybenzoic, benzene-1,2,4,5-tetracarboxylic, trimesic, and 5-hydroxyisophthalic acids were obtained through ball milling experiments. The optimal conditions for the milling process were chosen by changing the solvent volume and the mechanical action time. Supramolecular interactions in the new cocrystals are detailed based on single-crystal X-ray diffraction analysis, confirming the expected formation of hydrogen bonds between the praziquantel carbonyl group and the carboxyl (or hydroxyl) moieties of the coformers. Different structural characterization techniques were performed for all samples, but the praziquantel:suberic acid cocrystal includes a wider range of investigations such as thermal analysis, infrared and X-ray photoelectron spectroscopies, and SEM microscopy. The stability for up to five months was established by keeping it under extreme conditions of temperature and humidity. Solubility studies were carried out for all the new forms disclosed herein and compared with the promising cocrystals previously reported with salicylic, 4-aminosalicylic, vanillic, and oxalic acids. HPLC analyses revealed a higher solubility for most of the new cocrystal forms, as compared to pure praziquantel.
PubMed: 38855579
DOI: 10.1021/acs.cgd.4c00296 -
ACS Medicinal Chemistry Letters Nov 2023The anthelmintic drug praziquantel remains a key clinical therapy for treating various diseases caused by parasitic flatworms. The parasite target of praziquantel has...
The anthelmintic drug praziquantel remains a key clinical therapy for treating various diseases caused by parasitic flatworms. The parasite target of praziquantel has remained undefined despite longstanding usage in the clinic, although a candidate ion channel target, named TRPM, has recently been identified. Intriguingly, certain praziquantel derivatives show different activities against different parasites: for example, some praziquantel analogs are considerably more active against cestodes than against schistosomes. Here we interrogate whether the different activities of praziquantel analogs against different parasites are also reflected by unique structure-activity relationships at the TRPM channels found in these different organisms. To do this, several praziquantel analogs were synthesized and functionally profiled against schistosome and cestode TRPM channels. Data demonstrate that structure-activity relationships are closely mirrored between parasites and their TRPM orthologs, providing further support for TRPM as the therapeutically relevant target of praziquantel.
PubMed: 37970586
DOI: 10.1021/acsmedchemlett.3c00350 -
BioRxiv : the Preprint Server For... Nov 2023We previously performed a genome-wide association study (GWAS) to identify the genetic basis of praziquantel (PZQ) response in schistosomes, identifying two quantitative...
We previously performed a genome-wide association study (GWAS) to identify the genetic basis of praziquantel (PZQ) response in schistosomes, identifying two quantitative trait loci (QTL) situated on chromosome 2 and chromosome 3. We reanalyzed this GWAS using the latest (v10) genome assembly showing that a single locus on chromosome 3, rather than two independent loci, determines drug response. These results reveal that praziquantel response is monogenic and demonstrates the importance of high-quality genomic information.
PubMed: 37961217
DOI: 10.1101/2023.11.01.565202 -
PLoS Neglected Tropical Diseases Jan 2024Malaria and schistosomiasis are two important parasitic diseases that are a particular threat to young children and pregnant women in sub-Saharan Africa. Malaria and... (Review)
Review
Malaria and schistosomiasis are two important parasitic diseases that are a particular threat to young children and pregnant women in sub-Saharan Africa. Malaria and schistosomiasis prevention and control strategies primarily focus on the distribution of long-lasting insecticidal nets and the delivery of praziquantel tablets to at-risk populations in high burden settings through mass drug administration, respectively. The objective of this scoping review was to identify previous efforts to integrate malaria and schistosomiasis prevention and control programs in the literature and to summarize the strategies and approaches used in these programs following the PRISMA-ScR guidelines. We reviewed published and grey literature using a combination of keywords and search terms following themes surrounding "malaria", "Plasmodium falciparum", "Anopheles", "schistosomiasis", "Schistosoma haematobium", "Schistosoma mansoni", and "snails". Neither a date limit nor relevant terms for prevention and control were used. Out of 6374, eight articles were included in the scoping review-three articles investigated the integration of mass drug administration for schistosomiasis with the administration of antimalarials, four articles investigated the effect of administering antimalarials on malaria, schistosomiasis, and their co-infection, and one article assessed the impact of an educational intervention on malaria and schistosomiasis knowledge and preventative behaviors. Our findings suggest that there is an opportunity to link disease control programs to increase access and coverage of interventions to improve outcomes for malaria, schistosomiasis, and their co-infection. Further research is needed on the potential benefits, feasibility, and cost-effectiveness of integrating malaria and schistosomiasis prevention and control programs.
Topics: Pregnancy; Child; Animals; Humans; Female; Child, Preschool; Antimalarials; Coinfection; Malaria; Schistosomiasis; Schistosoma haematobium
PubMed: 38265982
DOI: 10.1371/journal.pntd.0011886