-
Nature Structural & Molecular Biology May 2024Diseases caused by parasitic flatworms impart a considerable healthcare burden worldwide. Many of these diseases-for example, the parasitic blood fluke infection...
Diseases caused by parasitic flatworms impart a considerable healthcare burden worldwide. Many of these diseases-for example, the parasitic blood fluke infection schistosomiasis-are treated with the drug praziquantel (PZQ). However, PZQ is ineffective against disease caused by liver flukes from the genus Fasciola because of a single amino acid change within the target of PZQ, a transient receptor potential ion channel in the melastatin family (TRPM), in Fasciola species. Here, we identify benzamidoquinazolinone analogs that are active against Fasciola TRPM. Structure-activity studies define an optimized ligand (BZQ) that caused protracted paralysis and tegumental damage to these liver flukes. BZQ also retained activity against Schistosoma mansoni comparable to PZQ and was active against TRPM orthologs in all profiled species of parasitic fluke. This broad-spectrum activity manifests as BZQ adopts a pose within the binding pocket of TRPM that is dependent on a ubiquitously conserved residue. BZQ therefore acts as a universal activator of trematode TRPM and a first-in-class, broad-spectrum flukicide.
PubMed: 38714890
DOI: 10.1038/s41594-024-01298-3 -
BioRxiv : the Preprint Server For... Apr 2024The bitter taste of medicines hinders patient compliance, but not everyone experiences these difficulties because people worldwide differ in their bitterness perception....
The bitter taste of medicines hinders patient compliance, but not everyone experiences these difficulties because people worldwide differ in their bitterness perception. To better understand how people from diverse ancestries perceive medicines and taste modifiers, 338 adults, European and recent US and Canada immigrants from Asia, South Asia, and Africa, rated the bitterness intensity of taste solutions on a 100-point generalized visual analog scale and provided a saliva sample for genotyping. The taste solutions were five medicines, tenofovir alafenamide (TAF), moxifloxacin, praziquantel, amodiaquine, and propylthiouracil (PROP), and four other solutions, TAF mixed with sucralose (sweet, reduces bitterness) or 6-methylflavone (tasteless, reduces bitterness), sucralose alone, and sodium chloride alone. Bitterness ratings differed by ancestry for two of the five drugs (amodiaquine and PROP) and for TAF mixed with sucralose. Genetic analysis showed that people with variants in one bitter receptor variant gene (38) reported PROP was more bitter than did those with a different variant (p= 7.6e-19) and that people with either an or a genotype found sucralose more bitter than did others (p=2.6e-8, p=7.9e-11, resp.). Our findings may help guide the formulation of bad-tasting medicines to meet the needs of those most sensitive to them.
PubMed: 38712219
DOI: 10.1101/2024.04.24.590957 -
Fish & Shellfish Immunology Jun 2024Aporocotylids (Trematoda: Digenea), also known as fish blood flukes infect the circulatory system of fish leading to serious health problems and mortality. Aporocotylids... (Review)
Review
Aporocotylids (Trematoda: Digenea), also known as fish blood flukes infect the circulatory system of fish leading to serious health problems and mortality. Aporocotylids are a particular concern for farmed fish as infection intensity can increase within the farming environment and lead to mortalities. In the context of managing these infections, one of the most crucial aspects to consider is the host response of the infected fish against these blood flukes. Understanding the response is essential to improving current treatment strategies that are largely based on the use of anthelmintic praziquantel to manage infections in aquaculture. This review focuses on the current knowledge of farmed fish host responses against the different life stages of aporocotylids. New treatment strategies that are able to provide protection against reinfections should be a long-term goal and is not possible without understanding the fish response to infection and the interactions between host and parasite.
Topics: Animals; Trematode Infections; Fish Diseases; Trematoda; Aquaculture; Fishes; Host-Parasite Interactions; Anthelmintics
PubMed: 38710341
DOI: 10.1016/j.fsi.2024.109613 -
Experimental Parasitology Jul 2024Neurocysticercosis (NCC) is a parasitic infection caused by the larval stage of the pork tapeworm, Taenia solium. The complications of NCC include seizures, headaches,...
Neurocysticercosis (NCC) is a parasitic infection caused by the larval stage of the pork tapeworm, Taenia solium. The complications of NCC include seizures, headaches, cognitive impairment, and focal neurological deficits. In addition to antiparasitic drugs and surgery, the management of NCC includes the use of corticosteroids to reduce inflammation and control symptoms. The traditional treatment with albendazole and praziquantel has not been altered over 30 years and present several side effects. There are other anti-helminthic drugs such as oxfendazole and nitazoxanide that may show efficacy in NCC treatment. The aim of this study was to determine the histopathologic aspects of experimental NCC after in vivo treatment with the combination of oxfendazole and nitazoxanide. Balb/c mice were infected with T. crassiceps cysticerci and divided into groups of 10 animals each that received a single dose through gavage as follows: group treated with NaCl 0.9% (control group); group treated by monotherapy of the anti-helminthic drugs, 30 mg/kg in single dose of oxfendazole (OXF) or nitazoxanide (NTZ); and groups treated with the combination of the drugs (OXF/NTZ group). Macroscopic and microscopic analysis were performed. There was greater presence of final stage cysticerci after treatment. The microscopic analysis of the general pathological processes showed that the monotherapy with all treatment groups induced higher perivasculitis than what was observed in the control group. In contrast, the combination treatment showed a lower observation of PMN and MN inflammatory infiltration in comparison to the other treatments and to the control one. These results show that indeed the association of benzimidazole derivatives which present both anti-helminthic and anti-inflammatory properties with other cysticidal drugs are beneficial for the NCC treatment in which the aim is to destroy parasite without inducing inflammatory damage in the brain tissue.
Topics: Animals; Neurocysticercosis; Mice; Thiazoles; Mice, Inbred BALB C; Nitro Compounds; Benzimidazoles; Brain; Female; Drug Therapy, Combination; Anti-Inflammatory Agents; Anthelmintics; Taenia solium
PubMed: 38677580
DOI: 10.1016/j.exppara.2024.108764 -
ACS Infectious Diseases May 2024The term "zoonosis" denotes diseases transmissible among vertebrate animals and humans. These diseases constitute a significant public health challenge, comprising 61%... (Review)
Review
The term "zoonosis" denotes diseases transmissible among vertebrate animals and humans. These diseases constitute a significant public health challenge, comprising 61% of human pathogens and causing an estimated 2.7 million deaths annually. Zoonoses not only affect human health but also impact animal welfare and economic stability, particularly in low- and middle-income nations. Leishmaniasis and schistosomiasis are two important neglected tropical diseases with a high prevalence in tropical and subtropical areas, imposing significant burdens on affected regions. Schistosomiasis, particularly rampant in sub-Saharan Africa, lacks alternative treatments to praziquantel, prompting concerns regarding parasite resistance. Similarly, leishmaniasis poses challenges with unsatisfactory treatments, urging the development of novel therapeutic strategies. Effective prevention demands a One Health approach, integrating diverse disciplines to enhance diagnostics and develop safer drugs. Metalloenzymes, involved in parasite biology and critical in different biological pathways, emerged in the last few years as useful drug targets for the treatment of human diseases. Herein we have reviewed recent reports on the discovery of inhibitors of metalloenzymes associated with zoonotic diseases like histone deacetylases (HDACs), carbonic anhydrase (CA), arginase, and heme-dependent enzymes.
Topics: Animals; Humans; Leishmaniasis; Schistosoma; Zoonoses; Schistosomiasis; Leishmania; Carbonic Anhydrases; Histone Deacetylases; Enzyme Inhibitors
PubMed: 38669567
DOI: 10.1021/acsinfecdis.4c00163 -
Non-coding RNA Apr 2024Schistosomiasis is a disease caused by trematodes of the genus that affects over 200 million people worldwide. For decades, praziquantel (PZQ) has been the only...
Schistosomiasis is a disease caused by trematodes of the genus that affects over 200 million people worldwide. For decades, praziquantel (PZQ) has been the only available drug to treat the disease. Despite recent discoveries that identified a transient receptor ion channel as the target of PZQ, schistosome response to this drug remains incompletely understood, since effectiveness relies on other factors that may trigger a complex regulation of parasite gene expression. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with low or no protein-coding potential that play important roles in homeostasis, reproduction, and fertility. Here, we show that PZQ treatment modulates lncRNA levels in . We re-analyzed public RNA-Seq data from mature and immature worms treated with PZQ and detected hundreds of lncRNAs differentially expressed following drug exposure, many of which are shared among mature and immature worms. Through RT-qPCR, seven out of ten selected lncRNAs were validated as differentially expressed; interestingly, we show that these lncRNAs are not adult worm stage-specific and are co-expressed with PZQ-modulated protein-coding genes. By demonstrating that parasite lncRNA expression levels alter in response to PZQ, this study unravels an important step toward elucidating the complex mechanisms of response to PZQ.
PubMed: 38668385
DOI: 10.3390/ncrna10020027 -
Saudi Medical Journal Apr 2024Echinococcosis is a parasitic infection that is distributed worldwide. Its clinical presentation depends on the size and location of the cyst. A 7-year-old was found...
Echinococcosis is a parasitic infection that is distributed worldwide. Its clinical presentation depends on the size and location of the cyst. A 7-year-old was found with a superimposed infected pulmonary hydatid cyst that was initially misdiagnosed as complicated pneumonia. Our case underscores the challenges of diagnosing and managing echinococcosis, emphasizes the need for a high index of suspicion, and describes the disease's ability to mimic other clinical entities.
Topics: Humans; Echinococcosis, Pulmonary; Child; Male; Diagnosis, Differential; Tomography, X-Ray Computed
PubMed: 38657978
DOI: 10.15537/smj.2024.45.4.20230078 -
Iranian Journal of Parasitology 2024Schistosomiasis is a parasitic disease caused by trematodes (body flukes), affecting millions worldwide. However, its pulmonary manifestations are rare. We report a rare...
Schistosomiasis is a parasitic disease caused by trematodes (body flukes), affecting millions worldwide. However, its pulmonary manifestations are rare. We report a rare case of a 51-year-old People Living with HIV male, managed in a tertiary care hospital in west India in May 2023, vegetable vendor who was admitted with complaints of dysphagia, odynophagia, fever and chest pain for 3 days, cough and breathlessness for 1 month. Chest x-ray and CT scan were suggestive of hypodense fluid collection with rim enhancement along right lateral and posterior aspect of thoracic esophagus. All routine investigations and urine cultures were sent, which turned to be inconclusive. Upper Gastrointestinal scopy was suggestive of pangastritis. Fiberoptic bronchoscopy was done with no structural abnormality or endobronchial mass. Bronchoalveolar lavage from right lower lobe was sent for CBNAAT, Gram and Ziehl Nelson staining and cultures, acid fast bacilli cultures and cytology which revealed parasitic infection with . The patient was treated with tablet praziquantel P/O 2400 mg in divided doses for 1 day followed up after two weeks when he experienced reduced symptoms. Sputum examination was repeated showed on wet mount and hence a repeat dose of tablet praziquantel 3000 mg in divided doses was given and was advised to follow up 2 weeks later, which showed resolution of right lower zone opacities.
PubMed: 38654948
DOI: 10.18502/ijpa.v19i1.15219 -
International Maritime Health 2024Schistosomiasis, caused by Schistosoma trematode worms, represents a significant global health challenge. This review offers a thorough examination of the disease's... (Review)
Review
Schistosomiasis, caused by Schistosoma trematode worms, represents a significant global health challenge. This review offers a thorough examination of the disease's epidemiology, transmission dynamics, diagnostic modalities, and treatment options. Diagnostic techniques encompass direct parasitological methods, immunological assays, DNA/RNA detection, and biomarker utilization, each with distinct advantages and limitations. There is an urgent need for improved diagnostic tools with enhanced sensitivity and specificity. Praziquantel remains the cornerstone of treatment, exhibiting efficacy against all Schistosoma species, while the potential of artemisin derivatives in combination therapy is also explored. In this review, we focus on the importance of praziquantel administration as the central aspect of schistosomiasis treatment, highlighting ongoing efforts to optimize its utilization for improved patient outcomes.
Topics: Praziquantel; Humans; Schistosomiasis; Anthelmintics; Animals; Schistosoma
PubMed: 38647059
DOI: 10.5603/imh.99453 -
PLoS Neglected Tropical Diseases Apr 2024Schistosomiasis is endemic in Nigeria, and the treatment is largely concentrated on children enrolled in schools. Consequently, the coverage of non-enrolled school-aged...
Endemic status of urogenital schistosomiasis and the efficacy of a single-dose praziquantel treatment in unmapped rural farming communities in Oyo East Local Government Area, Oyo State, Nigeria.
BACKGROUND
Schistosomiasis is endemic in Nigeria, and the treatment is largely concentrated on children enrolled in schools. Consequently, the coverage of non-enrolled school-aged children is often neglected. Ajagba and Awosan are two communities in Nigeria that have never had any control intervention. Hence, this survey was designed to determine the endemicity of urogenital schistosomiasis and to evaluate the efficacy of a single-dose praziquantel in the communities.
METHODS
Urine sample (10 mL) of each participant from Ajagba and Awosan communities was filtered through 12μm polycarbonate filter. The filter was placed on a microscope slide, and stained with a drop of 1% Lugol iodine solution. The stained slides were examined under the microscope and the numbers of S. haematobium eggs were counted. Water contact sites were searched for snail hosts and the snails collected were shed for Schistosoma cercariae. Data were analyzed using SPSS version 24.0 and the significance level was set at 95%.
RESULTS
The overall prevalence of infection in the Ajagba community was 45.6% with a mean intensity of 61.1 ± 144.5 eggs/10 mL of urine, while the prevalence of infection in the Awosan community was 5.7% with a mean intensity of 1.4 ± 6.8 eggs/10 mL of urine. The school-aged children had a prevalence and mean intensity of infection of 73.1% and 111.6 ± 177.9 eggs/10 mL of urine, respectively. Following treatment, women had a higher egg reduction rate than men (p = 0.0283). Bulinus globosus were found in Ajagba but not in Awosan, with 5.7% shedding Schistosoma spp, cercariae.
CONCLUSION
Urogenital schistosomiasis was hyperendemic in the Ajagba community, and hypoendemic in the Awosan community. The presence of Bulinus globosus supported the transmission of the schistosomiasis in the Ajagba community. Communities where schistosomiasis is still actively transmitted in Nigeria should be identified for effective intervention through the MDA programs.
Topics: Nigeria; Humans; Praziquantel; Child; Schistosomiasis haematobia; Animals; Female; Male; Adolescent; Schistosoma haematobium; Rural Population; Anthelmintics; Adult; Young Adult; Prevalence; Snails; Child, Preschool; Middle Aged; Endemic Diseases; Parasite Egg Count
PubMed: 38620032
DOI: 10.1371/journal.pntd.0012101