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Antimicrobial Agents and Chemotherapy May 2024Schistosomiasis, a widespread parasitic disease caused by the blood fluke of the genus , affects over 230 million people, primarily in developing countries....
Schistosomiasis, a widespread parasitic disease caused by the blood fluke of the genus , affects over 230 million people, primarily in developing countries. Praziquantel, the sole drug currently approved for schistosomiasis treatment, demonstrates effectiveness against patent infections. A recent study highlighted the antiparasitic properties of amiodarone, an anti-arrhythmic drug, exhibiting higher efficacy than praziquantel against prepatent infections. This study assessed the efficacy of amiodarone and praziquantel, both individually and in combination, against through comprehensive and experiments. experiments demonstrated synergistic activity (fractional inhibitory concentration index ≤0.5) for combinations of amiodarone with praziquantel. In a murine model of schistosomiasis featuring prepatent infections, treatments involving amiodarone (200 or 400 mg/kg) followed by praziquantel (200 or 400 mg/kg) yielded a substantial reduction in worm burden (60%-70%). Given the low efficacy of praziquantel in prepatent infections, combinations of amiodarone with praziquantel may offer clinical utility in the treatment of schistosomiasis.
PubMed: 38780260
DOI: 10.1128/aac.00114-24 -
Infection Oct 2023Currently, there are no standardized guidelines for the diagnosis or management of the complications of urogenital schistosomiasis (UGS). This systematic review of the... (Review)
Review
BACKGROUND
Currently, there are no standardized guidelines for the diagnosis or management of the complications of urogenital schistosomiasis (UGS). This systematic review of the literature aims to investigate the state of the art in reference to diagnostic approaches and the clinical management of this condition.
METHODS
A systematic review of literature published between January 1990 and January 2021 was conducted in the MEDLINE database, scoping for articles regarding diagnostic means or therapeutic options for the complications of UGS, namely obstructive uropathy, bladder cancer, abortion, ectopic pregnancy, infertility, kidney failure, urolithiasis and the need for invasive procedures. Relevant data were then extracted from the articles deemed eligible according to the inclusion criteria.
MAIN RESULTS
In total, 3052 articles were identified by the research query, of which 167 articles fulfilling inclusion criteria after title/abstract screening and full-text evaluation were included, 35% on both diagnostic and therapeutic aspects, and 51% on diagnosis and 14% on therapy. Ultrasound was the most frequently tool employed for the diagnosis of UGS complications showing a good performance. Concerning the management of hydronephrosis, the majority of available evidences came from community-based studies where universal treatment with praziquantel was used leading to decrease of prevalence of obstructive uropathy. Concerning studies on surgical procedures, laser endoureterotomy followed by stenting was mostly employed in adult patients leading to a crude cure rate of 60% (43 of 71 patients). In the case of severe hydronephrosis, surgery consisting of ureteral re-implantation showed excellent results with a crude cure rate of 98% (157 cured patients of 160 treated). Concerning bladder cancer, data on 93 patients with a clear diagnosis of UGS-related bladder were available reporting a variable and sometime combined approach based on disease stage. Available data on diagnosis and management of abortion, ectopic pregnancy, infertility, kidney failure, urolithiasis and the need for invasive procedures due to UGS are also presented.
CONCLUSIONS
The review produced a complete picture of the diagnostic and therapeutic options currently available for complicated UGS. These results can be useful both for guiding clinicians towards correct management and for tracing the direction of future research.
Topics: Female; Pregnancy; Adult; Humans; Schistosomiasis haematobia; Hydronephrosis; Infertility; Pregnancy, Ectopic; Renal Insufficiency; Urinary Bladder Neoplasms; Urolithiasis
PubMed: 37466786
DOI: 10.1007/s15010-023-02060-5 -
Clinical Microbiology Reviews Mar 2024, , and are important liver flukes that cause a considerable public health burden in eastern Asia, southeastern Asia, and eastern Europe, respectively. The life cycles... (Review)
Review
, , and are important liver flukes that cause a considerable public health burden in eastern Asia, southeastern Asia, and eastern Europe, respectively. The life cycles are complex, involving humans, animal reservoirs, and two kinds of intermediate hosts. An interplay of biological, cultural, ecological, economic, and social factors drives transmission. Chronic infections are associated with liver and biliary complications, most importantly cholangiocarcinoma. With regard to diagnosis, stool microscopy is widely used in epidemiologic surveys and for individual diagnosis. Immunologic techniques are employed for screening purposes, and molecular techniques facilitate species differentiation in reference laboratories. The mainstay of control is preventive chemotherapy with praziquantel, usually combined with behavioral change through information, education and communication, and environmental control. Tribendimidine, a drug registered in the People's Republic of China for soil-transmitted helminth infections, shows potential against both and and, hence, warrants further clinical development. Novel control approaches include fish vaccine and biological control. Considerable advances have been made using multi-omics which may trigger the development of new interventions. Pressing research needs include mapping the current distribution, disentangling the transmission, accurately estimating the disease burden, and developing new diagnostic and treatment tools, which would aid to optimize control and elimination measures.
Topics: Animals; Humans; Opisthorchiasis; Clonorchiasis; Clonorchis sinensis; Opisthorchis; Morbidity
PubMed: 38169283
DOI: 10.1128/cmr.00009-23 -
Molecules (Basel, Switzerland) Sep 2023It is estimated that 250 million people worldwide are affected by schistosomiasis. Disease transmission is related to the poor sanitation and hygiene habits that affect... (Review)
Review
It is estimated that 250 million people worldwide are affected by schistosomiasis. Disease transmission is related to the poor sanitation and hygiene habits that affect residents of impoverished regions in tropical and subtropical countries. The main species responsible for causing disease in humans are , , and , each with different geographic distributions. Praziquantel is the drug predominantly used to treat this disease, which offers low effectiveness against immature and juvenile parasite forms. In addition, reports of drug resistance prompt the development of novel therapeutic approaches. Natural products represent an important source of new compounds, especially those obtained from plant sources. This review compiles data from several in vitro and in vivo studies evaluating various compounds and essential oils derived from plants with cercaricidal and molluscicidal activities against both juvenile and adult forms of the parasite. Finally, this review provides an important discussion on recent advances in molecular and computational tools deemed fundamental for more rapid and effective screening of new compounds, allowing for the optimization of time and resources.
Topics: Humans; Animals; Anthelmintics; Schistosoma haematobium; Biological Products; Schistosomiasis; Praziquantel; Schistosoma mansoni
PubMed: 37836650
DOI: 10.3390/molecules28196807 -
Journal of Agricultural and Food... Aug 2023Praziquantel (PZQ) is administered as a racemic mixture during swine production to treat parasitic diseases. Despite its widespread application, the pharmacokinetics,...
Praziquantel (PZQ) is administered as a racemic mixture during swine production to treat parasitic diseases. Despite its widespread application, the pharmacokinetics, residue depletion, bioactivity, and toxicity of PZQ enantiomers in swine remain largely unknown. In this study, a systematic investigation of the pharmacokinetics, tissue distribution, and residue depletion of PZQ, its major metabolites (- and -4-OH-PZQ), and their enantiomers was conducted in swine. The findings indicated that PZQ was absorbed and metabolized rapidly. In swine plasma, the concentrations of -PZQ, --4-OH-PZQ, and --4-OH-PZQ were higher than those of their respective enantiomers. The three analytes exhibited significant tissue distribution and stereoselectivity in 10 swine tissues. Notably, the two enantiomers of PZQ demonstrated comparable tissue concentrations except in the liver and lung. Moreover, the concentrations of --4-OH-PZQ and --4-OH-PZQ were higher than those of their respective enantiomers in the 10 tissues. This study has significant implications for the development of rational dosing strategies, reducing drug usage, and minimizing side effects, as well as accurately assessing the risks associated with PZQ administration and, by extension, other chiral drugs. Furthermore, it lays a theoretical foundation for the future use of the active enantiomer, -PZQ.
Topics: Animals; Swine; Praziquantel; Liver; Stereoisomerism
PubMed: 37524372
DOI: 10.1021/acs.jafc.3c03546 -
Clinical Therapeutics Apr 2024The bad bitter taste of some medicines is a barrier to overcoming noncompliance with medication use, especially life-saving drugs given to children and the elderly....
PURPOSE
The bad bitter taste of some medicines is a barrier to overcoming noncompliance with medication use, especially life-saving drugs given to children and the elderly. Here, we evaluated a new class of bitter blockers (thiazolidinediones, TZDs).
METHODS
In this study, 2 TZDs were tested, rosiglitazone (ROSI) and a simpler form of TZD, using a high-potency sweetener as a positive control (neohesperidin dihydrochalcone, NHDC). We tested bitter-blocking effects using the bitter drugs tenofovir alafenamide fumarate (TAF), a treatment for HIV and hepatitis B infection, and praziquantel (PRAZ), a treatment for schistosomiasis, by conducting taste testing with 2 separate taste panels: a general panel (N = 97, 20-23 years, 82.5% female, all Eastern European) and a genetically informative panel (N = 158, including 68 twin pairs, 18-82 years, 76% female, 87% European ancestry). Participants rated the bitterness intensity of the solutions on a 100-point generalized visual analog scale.
FINDINGS
Person-to-person differences in drug bitterness were striking; TAF and PRAZ were weakly or not bitter for some people but moderately to highly bitter for others. Participants in both taste panels rated the bitter drugs TAF and PRAZ as less bitter on average when mixed with NHDC than when sampled alone. ROSI partially suppressed the bitterness of TAF and PRAZ, but effectiveness differed between the 2 panels: bitterness was significantly reduced for PRAZ but not TAF in the general panel and for TAF but not PRAZ in the genetically informative panel. ROSI was a more effective blocker than the other TZD.
IMPLICATIONS
These results suggest that TZDs are partially effective bitter blockers and the suppression efficacy differs from drug to drug, from person to person, and from panel to panel, suggesting other TZDs should be designed and tested with more drugs and on diverse populations to define which ones work best with which drugs and for whom. The discovery of bitter receptor blockers can improve compliance with medication use.
Topics: Humans; Female; Male; Taste; Adult; Aged; Middle Aged; Young Adult; Adolescent; Aged, 80 and over; Thiazolidinediones; Tenofovir; Rosiglitazone; Alanine
PubMed: 38462427
DOI: 10.1016/j.clinthera.2024.02.002 -
Journal of Parasitic Diseases :... Jun 2024Echinochasmidae are considered one of the digenean intestinal parasites of carnivorous mammals and humans. Some larvicidal medications, such as praziquantel and...
Echinochasmidae are considered one of the digenean intestinal parasites of carnivorous mammals and humans. Some larvicidal medications, such as praziquantel and albendazole, were employed to interrupt the life cycle of Echinochasmidae, which may cause harmful and serious effects on the domestic fish, ducks, and humans in our ecosystem. Cercariae of sp. (gymnocephalus type) were harvested by exposing snails to strong artificial illumination. The emerging cercariae were exposed in vitro to different concentrations of praziquantel and albendazole at the same period of incubation 12 h. Using probit analysis in SPSS version 25, the lethal concentrations 50 and 95% were determined. They were 0.036 and 0.82 ppm, respectively, for praziquantel and 5.3 and 9.2 ppm, respectively, for albendazole. The ultrastructural changes using scanning electron microscope on the tegumental surface of the treated cercariae with the two drugs were compared to the untreated cercariae. The untreated cercariae have a pear-shaped body with a long tail. The oral sucker is armed with a spiny collar and decorated with ciliated and unciliated sensory papillae. The cardinal ventral sucker has a thick, muscular wall. The cercarial tail is decorated with parallel longitudinal tegumental processes and spherical, unciliated papillae. In comparisons, cercariae treated with both drugs lost all healthy morphological features, but in varying degrees and effects between the two drugs. Our findings suggest that the use of both drugs can be recommended during the design of control strategies to combat this type of intestinal parasite.
PubMed: 38840870
DOI: 10.1007/s12639-024-01670-6 -
Pathogens and Global Health Oct 2023Praziquantel (PZQ) has been extensively used as the drug of choice for the treatment of schistosomiasis on account of its safety and effectiveness against all major...
Praziquantel (PZQ) has been extensively used as the drug of choice for the treatment of schistosomiasis on account of its safety and effectiveness against all major forms of schistosomiasis. However, low cure rate, reduced susceptibility of to PZQ and treatment failures in . infections have been reported, raising concerns about its efficacy. Using the search terms, 'praziquantel efficacy, schistosomiasis, school children, reinfection' as well as defined inclusion criteria, and guided by the PRISMA guidelines, articles from 2001 to 2022 were selected from the PubMed and Google Scholar databases and reviewed to assess their importance to the research question. This review assessed the efficacy of PZQ against schistosomiasis and reinfection rates following treatment of infections in children. Majority of both intestinal and urinary schistosomiasis studies reported comparable egg reduction rates (ERRs) of 94.2% to 99.9% and 91.9% to 98%, respectively. However, ERRs suggestive of sub-optimal PZQ efficacy as well as generally high and comparable cure rates for intestinal (81.2%-99.1%) and urinary (79%-93.7%) schistosomiasis studies were reported. Schistosomiasis reinfection rates varied widely for urinary (8.1%-39.6%) and intestinal (13.9%-63.4%) studies within eight to 28 weeks following PZQ treatment. Praziquantel treatment of urinary and intestinal schistosomiasis should be accompanied by the provision of potable water, toilet, and recreational facilities to reduce reinfection and egg reduction rates and increase cure rate to expedite schistosomiasis elimination.
Topics: Child; Humans; Praziquantel; Schistosomiasis mansoni; Anthelmintics; Reinfection; Treatment Outcome; Schistosomiasis haematobia
PubMed: 36394218
DOI: 10.1080/20477724.2022.2145070 -
European Journal of Medical Research Jul 2023Infection with Schistosoma sp. during pregnancy can cause low birth weight of the newborn. To allow a better differentiation between newborns with low birth weight and...
Infection with Schistosoma sp. during pregnancy can cause low birth weight of the newborn. To allow a better differentiation between newborns with low birth weight and those with normal weight, the terms of intrauterine growth restriction (IUGR), small for gestational age (SGA) or fetal growth restriction (FGR) should be used. FGR describes the relationship between birth weight and gestational age and is defined as the incapability of a fetus to achieve expected growth with birth weight below the 10th percentile for gestational age. Additional investigations of the proportion of newborns with FGR should obtain more certainty about the effect of praziquantel and schistosomiasis on fetal growth.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Praziquantel; Birth Weight; Schistosomiasis; Fetus
PubMed: 37434209
DOI: 10.1186/s40001-023-01202-7 -
Parasitology Research Apr 2024Because of recent reports of praziquantel resistance in schistosome infections, there have been suggestions to employ ivermectin as a possible alternative, especially as...
Because of recent reports of praziquantel resistance in schistosome infections, there have been suggestions to employ ivermectin as a possible alternative, especially as its chemical composition is different from that of praziquantel, so cross-resistance is not expected. In order to ascertain possible damage and elimination of worms, we used ivermectin by oral gavage in infected mice, at a high dose (30.1 mg/kg, bordering toxicity). We also tested the efficacy of the drug at various times postinfection (PI), to check on possible effect on young and mature stages of the parasites. Thus, we treated mice on days 21 and 22 or on days 41 and 42 and even on days 21, 22, 41, and 42 PI. None of the treatment regimens resulted in cure rates or signs of lessened pathology in the mice. We also compared the effect of ivermectin to that of artemisone, an artemisinin derivative which had served us in the past as an effective anti-schistosome drug, and there was a stark difference in the artemisone's efficacy compared to that of ivermectin; while ivermectin was not effective, artemisone eliminated most of the worms, prevented egg production and granulomatous inflammatory response. We assume that the reported lack of activity of ivermectin, in comparison with praziquantel and artemisinins, originates from the difference in their mode of action. In wake of our results, we suggest that ivermectin is not a suitable drug for treatment of schistosomiasis.
Topics: Animals; Mice; Praziquantel; Ivermectin; Schistosomiasis; Artemisinins; Schistosomatidae
PubMed: 38592544
DOI: 10.1007/s00436-024-08178-1