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BMJ Case Reports Feb 2015
Topics: Adult; Albendazole; Anthelmintics; Diagnosis, Differential; Echinococcosis; Humans; Liver; Lung; Male; Peritoneal Cavity; Praziquantel; Retroperitoneal Space; Tomography, X-Ray Computed; Ultrasonography
PubMed: 25725031
DOI: 10.1136/bcr-2014-208839 -
Parasites & Vectors Oct 2021Schistosomiasis is a debilitating and neglected tropical disease for which praziquantel (PZQ) remains the first-choice drug for treatment and control of the disease. In...
BACKGROUND
Schistosomiasis is a debilitating and neglected tropical disease for which praziquantel (PZQ) remains the first-choice drug for treatment and control of the disease. In our previous studies, we found that the patented compound DW-3-15 (patent no. ZL201110142538.2) displayed significant and stabilized antiparasitic activity through a mechanism that might be distinct from PZQ. Here, we investigated the antischistosomal efficacy of PZQ combined with DW-3-15 against schistosomula and adult worms of Schistosoma japonicum in vitro and in vivo, to verify whether there was a synergistic effect of the two compounds.
METHODS
The antischistosomal efficacy of PZQ combined with DW-3-15 in comparison with an untreated control and monotherapy group against schistosomula and adult worms was assessed both in vitro and in vivo. Parasitological studies, scanning electron microscopy, combination index, and histopathological analysis were used for the assessment.
RESULTS
The results showed significantly reduced viability of schistosomes, achieving 100% viability reduction for juveniles and males by combination chemotherapy using PZQ together with DW-3-15 in vitro. The combination index was 0.28, 0.27, and 0.53 at the higher concentration of PZQ combined with DW-3-15 against juveniles, males, and females, respectively, indicating that the two compounds display strong synergism. Scanning electron microscopy observations also demonstrated that the compound combination induced more severe and extensive alterations to the tegument and subtegument of S. japonicum than those with each compound alone. In vivo, compared with the single-compound-treated group, the group treated with the higher-dose combination demonstrated the best schistosomicidal efficacy, with significantly reduced worm burden, egg burden, and granuloma count and area, which was evident against schistosomula and adult worms.
CONCLUSIONS
Our study provides a potential novel chemotherapy for schistosomiasis caused by S. japonicum. It would improve the antischistosomal effect on schistosomula and adult worms of S. japonicum, and decrease individual dosages.
Topics: Animals; Drug Synergism; Drug Therapy, Combination; Female; Mice, Inbred ICR; Parasite Egg Count; Praziquantel; Schistosoma japonicum; Schistosomicides; Mice
PubMed: 34702326
DOI: 10.1186/s13071-021-05065-x -
PLoS Neglected Tropical Diseases Sep 2020Schistosomiasis control is heavily reliant on the drug praziquantel (PZQ), which is used as preventive chemotherapy as part of national helminth control strategies.... (Review)
Review
Schistosomiasis control is heavily reliant on the drug praziquantel (PZQ), which is used as preventive chemotherapy as part of national helminth control strategies. Given the heavy reliance on PZQ for mass drug administration, there has been considerable research on the potential of parasites developing resistance to the drug, resulting in decreased drug efficacy. However, there have been comparatively fewer studies of other factors that can potentially alter PZQ efficacy. Here, we investigate whether host PZQ metabolism contributes towards variable cure rates. We evaluate factors that can influence the metabolism of PZQ and the resultant effect on the efficacy of PZQ treatment to determine factors that potentially influence an individual's response to the drug. The literature search was directed at published studies from three online databases: Web of Science, PubMed, and EMBASE. The search terms for the review comprised of ([praziquantel OR PZQ] AND [schistosom* OR bilharzia] AND [pharmaco*]) and included studies evaluating PZQ metabolism. Publications were categorised into pharmacokinetics, drug-drug interactions, pharmacogenetics, and metabolite analysis. Forty publications describing human and experimental studies fitted the inclusion criteria and were subjected to data extraction and analysis. The analyses showed that variable exposure to PZQ was associated with alterations in the liver's capacity to metabolise PZQ and observed drug-drug interactions. Other factors influencing the efficacy of PZQ were brand, formulation, and co-administered food. Although some work has been performed on metabolite identification, there was minimal information on PZQ's metabolic pathway, and no pharmacogenetics studies were identified. The study indicated that in both human and experimental studies alterations in the liver's capacity to metabolise PZQ as well as drug-drug interactions affected systemic levels of PZQ that could result in variable cure rates. The study confirmed previous findings of higher antischistosomal activity of (R)-PZQ enantiomer when administered alone compared to the racemate at the same dose as well as improved efficacy when the drug is administered with food. The study also highlighted the need for more comprehensive studies of the PZQ metabolic pathway and PZQ pharmacogenetic studies in humans.
Topics: Animals; Anthelmintics; Disease Models, Animal; Humans; Praziquantel; Schistosoma mansoni; Schistosomiasis
PubMed: 32976496
DOI: 10.1371/journal.pntd.0008649 -
Parasites & Vectors Mar 2015Schistosomiasis is a disease caused by infection with blood flukes of the genus Schistosoma. Transmission of, and exposure to, the parasite result from faecal or urinary... (Review)
Review
Schistosomiasis is a disease caused by infection with blood flukes of the genus Schistosoma. Transmission of, and exposure to, the parasite result from faecal or urinary contamination of freshwater containing intermediate host snails, and dermal contact with the same water. The World Health Assembly resolution 65.21 from May 2012 urges member states to eliminate schistosomiasis through preventive chemotherapy (i.e. periodic large-scale administration of the antischistosomal drug praziquantel to school-aged children and other high-risk groups), provision of water, sanitation and hygiene (WASH) and snail control. However, control measures focus almost exclusively on preventive chemotherapy, while only few studies made an attempt to determine the impact of upgraded access to safe water, adequate sanitation and good hygiene on schistosome transmission. We recently completed a systematic review and meta-analysis pertaining to WASH and schistosomiasis and found that people with safe water and adequate sanitation have significantly lower odds of a Schistosoma infection. Importantly though, the transmission of schistosomiasis is deeply entrenched in social-ecological systems, and hence is governed by setting-specific cultural and environmental factors that determine human behaviour and snail populations. Here, we provide a comprehensive review of the literature, which explores the transmission routes of schistosomes, particularly focussing on how these might be disrupted with WASH-related technologies and human behaviour. Additionally, future research directions in this area are highlighted.
Topics: Animals; Child; Fresh Water; Global Health; Humans; Hygiene; Male; Praziquantel; Sanitation; Schistosoma; Schistosomiasis; Snails; Water
PubMed: 25884172
DOI: 10.1186/s13071-015-0766-9 -
Infectious Diseases of Poverty Jul 2018Schistosomiasis is a serious public health burden in sub-Saharan Africa. Praziquantel is the only drug recommended by the World Health Organization to treat both... (Review)
Review
BACKGROUND
Schistosomiasis is a serious public health burden in sub-Saharan Africa. Praziquantel is the only drug recommended by the World Health Organization to treat both urogenital and intestinal schistosomiasis. The reliance on a single drug to treat a disease with such a huge burden has raised concerns of possible drug resistance mainly in endemic areas. This systematic review was conducted to identify gaps and recent progress on the efficacy of different regimens of praziquantel in treating schistosomiasis among children in sub-Saharan Africa where Schistosoma mansoni and S. haematobium are endemic.
MAIN TEXT
A literature search of peer-reviewed journals was done on Google Scholar, MEDLINE (under EBSCOhost) and PubMed databases using pre-defined search terms and Boolean operators. The search included studies published from 2008 to 2017 (August) with emphasis on the efficacy of praziquantel on S. haematobium and S. mansoni infections among preschool and school children. Nineteen publications satisfied the inclusion criteria for the review. The studies reviewed were from 10 sub-Saharan African countries and 7/19 of the studies (37%) were conducted in Uganda. Seven studies (37%) focused on Schistosoma mansoni, 6/19 (31.5%) on S. haematobium and another 6 on mixed infection. A single standard dose of 40 mg/kg body weight was the most used regimen (9) followed by the repeated single standard dose assessed for efficacy at 3-4 weeks post-treatment.
CONCLUSIONS
A repeated standard dose of 40 mg/kg achieved satisfactory efficacy compared to a single dose against both parasite species. However, findings on efficacy of repeated doses in co-infection of S. mansoni and S. haematobium were not conclusive. Praziquantel administrated at 60 mg/kg was slightly more efficacious than the 40 mg/kg standard dose. Minor and transitory side-effects were reported for both regimens. The review indicates that further investigations are necessary to conclusively determine efficacy of praziquantel on coinfection of S. haematobium and S. mansoni to formulate concrete guidelines on the use of repeated doses at 40 or 60 mg/kg for treating schistosomiasis. We recommend the use of the egg reduction rate (ERR) formula recommended by the WHO for assessing praziquantel efficacy in order for the results to be comparable for different regions.
Topics: Africa South of the Sahara; Animals; Anthelmintics; Child; Child, Preschool; Humans; Praziquantel; Schistosoma haematobium; Schistosoma mansoni; Schistosomiasis
PubMed: 29986763
DOI: 10.1186/s40249-018-0448-x -
International Journal For Parasitology.... Aug 2023Ancylostoma caninum is the most common and important gastrointestinal nematode of dogs in the United States. Despite recent reports of A. caninum isolates resistant to...
Ancylostoma caninum is the most common and important gastrointestinal nematode of dogs in the United States. Despite recent reports of A. caninum isolates resistant to all classes of anthelmintics, little is known about the frequency and extent of this anthelmintic resistance. The study aim was to evaluate the efficacy of three commercial anthelmintic products in the treatment of foxhound dogs with a history of persistent A. caninum infections. In the first phase of this study, 35 foxhounds were randomly divided into three treatment groups: moxidectin/imidacloprid (MI), pyrantel pamoate/febantel/praziquantel (PFP), and emodepside/praziquantel (EP). Fecal samples were collected on day 0, 11, and 33 post-treatment (PT), and hookworm eggs were quantified using the mini-FLOTAC technique with a multiplication factor of 5 eggs per gram (EPG). The fecal egg count reduction (FECR) on day 11 PT was 65% (95% CI: 62%-68%) for MI, 69% (95% CI: 66%-72%) for PFP, and 96% (95% CI: 94%-97%) for EP. On day 33 PT, the FEC in the MI and PFP groups returned to almost the same values as on day 0, while in the EP group, the FEC remained low. Since MI and PFP proved ineffective, 32 animals were randomly divided into two groups in the second phase. They were treated either with a combination of MI/PFP or EP. The FECR at day 13 PT for the combination MI/PFP was 89% (95% CI: 87%-91%) and 99% (95% CI: 98%-99%) for EP. These results suggest that this A. caninum population is resistant to multiple anthelmintics. Although the combination of MI/PFP improved the anthelmintic efficacy, the FECR remained below 90%. Future studies are indicated to evaluate further the epidemiology of persistent hookworm infections in dogs in the US and to identify more effective treatment protocols as they pose a significant health risk to canine and human health.
Topics: Animals; Dogs; Ancylostoma; Ancylostomatoidea; Anthelmintics; Dog Diseases; Feces; Hookworm Infections; Nematoda; Parasite Egg Count; Praziquantel
PubMed: 37481894
DOI: 10.1016/j.ijpddr.2023.07.001 -
Parasites & Vectors Mar 2018Schistosomiasis is a neglected tropical disease burdening millions of people. One drug, praziquantel, is currently used for treatment and control. Clinically relevant... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Schistosomiasis is a neglected tropical disease burdening millions of people. One drug, praziquantel, is currently used for treatment and control. Clinically relevant drug resistance has not yet been described, but there is considerable heterogeneity in treatment outcomes, ranging from cure to only moderate egg reduction rates. The objectives of this study are to investigate potential worm-induced dysbacteriosis of the gut microbiota and to assess whether a specific microbiome profile could influence praziquantel response.
METHODS
Using V3 and V4 regions of 16S rRNA genes, we screened the gut microbiota of 34 Schistosoma mansoni infected and uninfected children from Côte d'Ivoire. From each infected child one pre-treatment, one 24-hour and one 21-day follow-up sample after administering 60 mg/kg praziquantel or placebo, were collected.
RESULTS
Overall taxonomic profiling and diversity indicators were found to be close to a "healthy" gut structure in all children. Slight overall compositional changes were observed between S. mansoni-infected and non-infected children. Praziquantel treatment was not linked to a major shift in the gut taxonomic profiles, thus reinforcing the good safety profile of the drug by ruling out off-targets effects on the gut microbes.16S rRNA gene of the Fusobacteriales order was significantly more abundant in cured individuals, both at baseline and 24 hours post-treatment. A real-time qPCR confirmed the over-abundance of Fusobacterium spp. in cured children. Fusobacterium spp. abundance could also be correlated with treatment induced S. mansoni egg-reduction.
CONCLUSIONS
Our study suggests that neither a S. mansoni infection nor praziquantel administration triggers a significant effect on the microbial composition and that a higher abundance of Fusobacterium spp., before treatment, is associated with higher efficacy of praziquantel in the treatment of S. mansoni infections.
TRIAL REGISTRATION
International Standard Randomised Controlled Trial, number ISRCTN15280205 .
Topics: Adolescent; Animals; Anthelmintics; Biodiversity; Child; Child, Preschool; Cote d'Ivoire; DNA Barcoding, Taxonomic; Feces; Female; Fusobacterium; Gastrointestinal Microbiome; Host-Parasite Interactions; Humans; Male; Praziquantel; RNA, Ribosomal, 16S; Schistosoma mansoni; Schistosomiasis mansoni; Treatment Outcome
PubMed: 29530088
DOI: 10.1186/s13071-018-2739-2 -
PLoS Neglected Tropical Diseases Aug 2014Both tribendimidine and mebendazole are broad-spectrum drugs for anti-intestinal nematodes. We aim to assess the efficacy and safety of tribendimidine and mebendazole in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Both tribendimidine and mebendazole are broad-spectrum drugs for anti-intestinal nematodes. We aim to assess the efficacy and safety of tribendimidine and mebendazole in patients with co-infection of Clonorchis sinensis and other helminths.
METHOD
We performed a randomized open-label trial in Qiyang, People's Republic of China. Eligible participants were randomly assigned to one of four groups: (i) a single dose of 400 mg tribendimidine, (ii) 200 mg tribendimidine twice daily, (iii) 75 mg/kg praziquantel divided in four doses within 2 days, and (iv) a single dose of 400 mg mebendazole. Cure rates and egg reduction rates were assessed, and adverse events were monitored after treatments. Uncured patients accepted the second treatment with the same drugs after the first treatment.
RESULTS
156 patients were eligible for the study. Results from the first treatment showed that the cure rates of single-dose tribendimidine and praziquantel against C. sinensis were 50% and 56.8%, respectively; the single-dose tribendimidine achieved the cure rate of 77.8% in the treatment for hookworm, which was significantly higher than that of praziquantel; Low cure rates were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura (28.6% and 23.1%). Results of the second treatment illustrated the cure rates of tribendimidine and praziquantel against C. sinensis were 78.1% and 75%, respectively. Most adverse events were mild and transient. Adverse events caused by tribendimidine were significantly less than praziquantel.
CONCLUSION
Single-dose tribendimidine showed similar efficacy against C. sinensis as praziquantel with less adverse events, and achieved significantly higher cure rate in the treatment for hookworm than those of praziquantel and mebendazole. Low cure rates, which were still higher than other drugs, were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura.
TRIAL REGISTRATION
Controlled-Trials.com ISRCTN55086560.
Topics: Adult; Animals; Anthelmintics; Ascariasis; Clonorchiasis; Coinfection; Female; Helminthiasis; Humans; Male; Mebendazole; Middle Aged; Phenylenediamines; Praziquantel
PubMed: 25122121
DOI: 10.1371/journal.pntd.0003046 -
Acta Medica Indonesiana Apr 2019A 46-years-old man from Indonesia, resides in Nagori Dolok Village, Silau Kahaean Subdistrict, Simalungun District, Sumatra Utara Province, had of spontaneous discharge...
A 46-years-old man from Indonesia, resides in Nagori Dolok Village, Silau Kahaean Subdistrict, Simalungun District, Sumatra Utara Province, had of spontaneous discharge of tapeworm segments (proglottids) from anus almost every day for ten years. There were 1-5 segments which can move actively discharge per day. Although he feels embarrassed about the condition, no significant symptoms were found, and physical examination was within normal limits. Clinical diagnosis of Taeniasis was made on October 20, 2017, and subsequently received oral Praziquantel 600 mg tablet single dose and 5 mg of oral Bisacodyl. Four hours later, the patient was defecated. The stool was collected in plastic and filtered with a filter device to collect any tapeworm segments.A full segment of tapeworm as long as 2.86 meters were found. Microscopic examination was done to identify the egg worms, proglottids, and scolex. Dye substance was injected into a mature gravid proglottid through the genital pore and pressed in two object-glasses to identify the reproductive organs. Microscopic examination (400x magnification) of this sample revealed that the number of uterine branches and testes in a proglottid were 16 pairs. The number of uterine branches in T. solium are 8-12 pairs and T. saginata are 18-32 pairs.The filtered stool was moved into a container and carefully observed. A soft yellowish-white material of 1.5 mm in diameter was found, which turned out to be the head of the tapeworm called Scolex. Microscopic examination of scolex revealed that the rostellum was absent. A segment called 'snout' was found at the apex. The functions were probably as a sense of smell and vacuum organ.The patient was lived in Simalungun, North Sumatera, some tribe in that area has a long tradition of culinary called 'Hinasumba', consist of raw pork liver and meat, and 'Naiholat' consist of poorly cooked pork.Even though pig was determined as an intermediate host, the type of tapeworm was not consistent with T.solium. The patient had the long history of infection but never had sign or symptoms of neurocystecercosis. Based on etno-geographical condition, the patient was infected by T.asiatica. Microscopic examination of the uterus and scolex indicate that the tapeworm had most similarity to T.asiatica.Amin et al.8 from Bangladesh in 2009 reported a case of T. asiatica in human with total strobila length was 1.5 meters. Macroscopic morphology (length:width) of gravid proglottid segment of T.saginata is 3:1, T. solium 1.5:1. The tapeworm that we discovered had 1-1.5:1 ratio (2.5 cm length and 2 cm width).Some features of the tapeworm (no rostellum, present of the snout, and fix number of theuterus in every proglottid) were not found in three existing type of Taenia species. Further microscopic and molecular study should be done to determined type or subtype of the tapeworm. A case of taeniasis asiatica who had completed treatment was reported. Macroscopic and microscopic was done to support the clinical diagnosis.
Topics: Animals; Anthelmintics; Feces; Humans; Indonesia; Male; Middle Aged; Praziquantel; Swine; Taenia; Taeniasis
PubMed: 31383834
DOI: No ID Found -
ACS Infectious Diseases May 2023In September 2022, the Drug Discovery Unit at the University of Dundee, UK, organised an international meeting at the Wellcome Collection in London to explore the... (Review)
Review
In September 2022, the Drug Discovery Unit at the University of Dundee, UK, organised an international meeting at the Wellcome Collection in London to explore the current clinical situation and challenges associated with treating schistosomiasis. The aim of this meeting was to discuss the need for new treatments in view of the clinical situation and to ascertain what the key requirements would be for any potential new anti-schistosomals. This information will be essential to inform ongoing drug discovery efforts for schistosomiasis. We also discussed the potential drug discovery pathway and associated criteria for progressing compounds to the clinic. To date, praziquantel (PZQ) is the only drug available to treat all species causing schistosomiasis, but it is often unable to completely clear parasites from an infected patient, partially due to its inactivity against juvenile worms. PZQ-mediated mass drug administration campaigns conducted in endemic areas (e.g., sub-Saharan Africa, where schistosomiasis is primarily prevalent) have contributed to reducing the burden of disease but will not eliminate the disease as a public health problem. The potential for to develop resistance towards PZQ, as the sole treatment available, could become a concern. Consequently, new anthelmintic medications are urgently needed, and this Perspective aims to capture some of the learnings from our discussions on the key criteria for new treatments.
Topics: Animals; London; Schistosomiasis; Praziquantel; Anthelmintics; Schistosoma
PubMed: 37083395
DOI: 10.1021/acsinfecdis.3c00081