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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 -
Infectious Diseases of Poverty Mar 2017The current approach of morbidity control of schistosomiasis, a helminth disease of poverty with considerable public health and socioeconomic impact, is based on... (Review)
Review
The current approach of morbidity control of schistosomiasis, a helminth disease of poverty with considerable public health and socioeconomic impact, is based on preventive chemotherapy with praziquantel. There is a pressing need for new drugs against this disease whose control entirely depends on this single drug that has been widely used over the past 40 years. We argue that a broader anthelminthic approach supplementing praziquantel with new antischistosomals targeting different parasite development stages would not only increase efficacy but also reduce the risk for drug resistance. Repositioning drugs already approved for other diseases provides a shortcut to clinical trials, as it is expected that such drugs rapidly pass the regulatory authorities. The antischistosomal properties of antimalarial drugs (e.g., semisynthetic artemisinins, synthetic trioxolanes, trioxaquines and mefloquine) and of drugs being developed or registered for other purposes (e.g., moxidectin and miltefosin), administered alone or in combination with praziquantel, have been tested in the laboratory and clinical trials. Another avenue to follow is the continued search for new antischistosomal properties in plants. Here, we summarise recent progress made in schistosomiasis chemotherapy, placing particular emphasis on repositioning of existing drugs against schistosomiasis.
Topics: Animals; Anthelmintics; Antimalarials; Drug Repositioning; Drug Resistance; Drug Therapy, Combination; Humans; Praziquantel; Public Health; Schistosoma; Schistosomiasis
PubMed: 28351414
DOI: 10.1186/s40249-017-0286-2 -
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 -
Parasite Immunology Nov 2022Schistosomiasis is still a major health problem affecting nearly 250 million people worldwide and causes approximately 280,000 deaths per year. The disease causes a...
Schistosomiasis is still a major health problem affecting nearly 250 million people worldwide and causes approximately 280,000 deaths per year. The disease causes a serious granulomatous inflammatory response that produces significant mortality. Plumbagin reportedly displays anti-inflammatory, anti-fibrotic, antioxidant and anthelmintic properties. This study further elucidates these properties. Mice were infected with schistosomes and divided into five groups: non-infected untreated (C); infected untreated (IU); non-infected treated with plumbagin (P); infected treated with plumbagin (PI) and infected treated with praziquantel (PZ). Mice treated with 20 mg plumbagin/kg body weight showed reduction of 64.28% and 59.88% in male and female animals, respectively. Also, the number of eggs/g tissue was reduced 69.39%, 68.79% and 69.11% in liver, intestine and liver/intestine combined, respectively. Plumbagin alleviated schistosome-induced hepatosplenomegaly and reduced hepatic granuloma and liver collagen content by 62.5% and 35.26%, respectively while PZQ reduced hepatic granuloma and liver collagen content by 41.11% and 11.21%, respectively. Further, plumbagin treatment significantly (p < .001) reduced IL-4, IL-13, IL-17, IL-37, IFN-γ, TGF-β and TNF-α levels and significantly (p < .001) upregulated IL-10. Plumbagin treatment restored hepatic enzymes activity to nearly normal levels and induced an increase in catalase, SOD, GSH, total thiol and GST in liver tissue homogenate. NO and LPO content was, however, decreased. Moreover, serum IgG levels significantly increased. The present study is the first to report immunomodulatory and schistosomicidal activities of plumbagin in schistosomiasis.
Topics: Animals; Anthelmintics; Anti-Inflammatory Agents; Antioxidants; Catalase; Female; Granuloma; Immunoglobulin G; Interleukin-10; Interleukin-13; Interleukin-17; Interleukin-4; Liver; Male; Mice; Naphthoquinones; Praziquantel; Schistosoma mansoni; Schistosomiasis; Schistosomiasis mansoni; Schistosomicides; Sulfhydryl Compounds; Superoxide Dismutase; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha
PubMed: 36066812
DOI: 10.1111/pim.12945 -
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 -
Acta Tropica Apr 2022Schistosomiasis is a public health issue of concern in Gabon, with the disease being reported from all regions of the country. The topic has been of interest for the... (Review)
Review
INTRODUCTION
Schistosomiasis is a public health issue of concern in Gabon, with the disease being reported from all regions of the country. The topic has been of interest for the local researchers and physicians for over two decades. The objective of this narrative review was to provide an overview of the research activities in the area from 2000 to early 2021.
METHODS
We performed a narrative literature review. The search strategy was designed to get a broad overview of the different research topics on schistosomiasis and the national control programme, and included grey literature.
RESULTS
A total of 159 articles was screened, and 42 were included into the review in addition to the grey literature. During the past two decades, the work on schistosomiasis originated from five out of the nine provinces of the country, with diverse aspects of the disease investigated; including immunology, epidemiology, diagnosis and treatment. Several studies investigated various aspects of schistosomiasis-related morbidity in the respective study populations. The body of work demonstrates that much effort was made to understand the details of the host immune response to schistosomiasis, and the immune profile changes induced in patients treated with praziquantel. Although some MDA campaigns were conducted in the country; little, however, is known on the epidemiological situation of the disease, particularly of its distribution within the population, as well as co-infections with other parasitic diseases also endemic in the area.
CONCLUSION
Progress has been made over the past two decades in the understanding of schistosomiasis in the country, including disease-related morbidity and its interaction with other parasitic infections, and the immunology and epidemiology of the disease. However, for optimising control of the disease, there is a need to fine-tune these findings with detailed local epidemiological and malacological data. We call for such studies to accomplish the knowledge of schistosomiasis in the country, particularly in areas of moderate or high endemicity, and recommend this approach to comparable schistosomiasis-endemic areas elsewhere.
Topics: Coinfection; Gabon; Humans; Morbidity; Praziquantel; Schistosomiasis
PubMed: 35051384
DOI: 10.1016/j.actatropica.2022.106317 -
Parasites & Vectors Oct 2023Schistosomiasis, also known as bilharzia, is a devastating parasitic disease. This progressive and debilitating helminth disease is often associated with poverty and can...
BACKGROUND
Schistosomiasis, also known as bilharzia, is a devastating parasitic disease. This progressive and debilitating helminth disease is often associated with poverty and can lead to chronic poor health. Despite ongoing research, there is currently no effective vaccine for schistosomiasis, and praziquantel remains the only available treatment option. According to the progression of schistosomiasis, infections caused by schistosomes are classified into three distinct clinical phases: acute, chronic and advanced schistosomiasis. However, the underlying immune mechanism involved in the progression of schistosomiasis remains poorly understood.
METHODS
We employed single-cell RNA sequencing (scRNA-seq) to profile the immune landscape of Schistosomiasis japonica infection based on peripheral blood mononuclear cells (PBMCs) from a healthy control group (n = 4), chronic schistosomiasis group (n = 4) and advanced schistosomiasis group (n = 2).
RESULTS
Of 89,896 cells, 24 major cell clusters were ultimately included in our analysis. Neutrophils and NK/T cells accounted for the major proportion in the chronic group and the healthy group, and monocytes dominated in the advanced group. A preliminary study showed that NKT cells were increased in patients with schistosomiasis and that CXCR2 + NKT cells were proinflammatory cells. Plasma cells also accounted for a large proportion of B cells in the advanced group. MHC molecules in monocytes were notably lower in the advanced group than in the chronic group or the healthy control group. However, monocytes in the advanced group exhibited high expression of FOLR3 and CCR2.
CONCLUSIONS
Overall, this study enhances our understanding of the immune mechanisms involved in schistosomiasis. It provides a transcriptional atlas of peripheral immune cells that may contribute to elimination of the disease. This preliminary study suggests that the increased presence of CCR2 + monocyte and CXCR2 + NKT cells might participate in the progression of schistosomiasis.
Topics: Humans; Schistosomiasis japonica; Schistosomiasis; Praziquantel; Natural Killer T-Cells; Sequence Analysis, RNA
PubMed: 37817226
DOI: 10.1186/s13071-023-05975-y -
Infectious Diseases of Poverty Feb 2018Chemotherapy for schistosomiasis has been around for 100 years. During the past century, great efforts have been made to develop new antischistosomal drugs from... (Review)
Review
BACKGROUND
Chemotherapy for schistosomiasis has been around for 100 years. During the past century, great efforts have been made to develop new antischistosomal drugs from antimonials to nonantimonials, and some of these have been used extensively in clinical treatment. With the exception of a few drugs, such as oxamniquine and metrifonate, most of the antischistosomals developed in the pre-praziquantel period have variable limitations with respect to safety and efficacy. Although oxamniquine and metrifonate have been used for schistosomiasis control, they are only effective against Schistosoma mansoni and S. haematobium, respectively. Currently, praziquantel is the only drug used for treatment of all five species of human schistosomes. In this review, the pharmacological and immunological effects of praziquantel against S. japonicum are summarized and discussed.
MAIN TEXT
From the end of the 1970s until the 2000s, scientists have conducted a series of experimental studies on the effects of praziquantel against S. japonicum. These have included examining its unique pharmacological action on schistosomes, the characteristics in susceptibility of the different developmental stages of schistosomes to the drug, the relationship between plasma concentration of the drug and efficacy, the impact of host factors on cidal action of the drug, prevention and early treatment of schistosomal infection, as well as praziquantel-resistant schistosomiasis.
CONCLUSION
The effects of praziquantel against S. japonicum, as elucidated by the experimental studies that are reviewed in this paper, may have some reference significance for the development of new antischistosomals.
Topics: Animals; Drug Resistance; Humans; Life Cycle Stages; Mice; Praziquantel; Schistosoma japonicum; Schistosoma mansoni; Schistosomiasis; Schistosomicides
PubMed: 29409536
DOI: 10.1186/s40249-018-0391-x