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PLoS Neglected Tropical Diseases Nov 2023Schistosomiasis is one of the most important neglected tropical diseases, with a great impact on public health and more than 200,000 deaths annually. Schistosoma...
BACKGROUND
Schistosomiasis is one of the most important neglected tropical diseases, with a great impact on public health and more than 200,000 deaths annually. Schistosoma haematobium causes urinary tract (UT) morbidity. Since schistosomiasis morbidity control programs focus on children older than 5 years, pre-school age children (PSAC) morbidity is not well known.
METHODS
We conducted a cross-sectional study in Cubal (Angola) among 245 PSAC with the objective of evaluating the prevalence of S. haematobium infection, the intensity of infection, and associated morbidity. For this purpose, urine filtration test followed by microscopic visualization and ultrasound examinations were performed.
RESULTS
The estimated overall prevalence of urogenital schistosomiasis was 30.2% (CI 95%; 24.5-35.9), with 20.3% (CI 95%; 15.3-25.3) of the samples analysed showing a high intensity of infection. A total of 54.5% (CI 95%; 47.6-61.8) of infected children presented UT lesions, showing a significant association between schistosomiasis infection and UT morbidity (p-value < 0.001). Bladder wall thickening was the most common lesion, being present in 100% of abnormal ultrasounds. We found that anaemia and severe malnutrition were not significantly associated with the development of UT lesions.
CONCLUSIONS
S. haematobium infection in PSAC causes great UT detectable morbidities. Therefore, there is an evident need of including them in mass drug administration (MDA) campaigns and consequently the development of an adapted praziquantel treatment dosage for children under 2 years of age.
Topics: Animals; Humans; Child; Child, Preschool; Infant; Schistosomiasis haematobia; Prevalence; Angola; Cross-Sectional Studies; Morbidity; Schistosoma haematobium
PubMed: 37939154
DOI: 10.1371/journal.pntd.0011751 -
Veterinary Parasitology, Regional... Nov 2023Dicrocoelium dendriticum is a trematode colonising the bile ducts of herbivores. Coproscopic findings in dogs are usually considered gastrointestinal passages of eggs...
Dicrocoelium dendriticum is a trematode colonising the bile ducts of herbivores. Coproscopic findings in dogs are usually considered gastrointestinal passages of eggs after ingestion of unheated liver tissue or infected ruminant faeces. Here, a Japanese Chin presented with diarrhoea and weight loss. Eggs comparable to D. dendriticum were detected in faeces and infection was confirmed via PCR and by ruling out differential diagnoses. Egg excretion continued for a period of 10 months. Praziquantel (50 mg/kg body weight [BW]) was administered orally for four consecutive days. Egg excretion 10 days after treatment entailed further treatments with 100 mg/kg BW, again for four days. Faecal samples were negative ten days and four weeks afterwards, diarrhoea resolved, and the dog gained weight. In cases of repeated coproscopic positivity for D. dendriticum, an infection with dogs acting as definitive hosts should be considered. Treatment with praziquantel at a higher dosage may be required.
Topics: Animals; Dogs; Diarrhea; Dicrocoeliasis; Dicrocoelium; Dog Diseases; Praziquantel
PubMed: 37935534
DOI: 10.1016/j.vprsr.2023.100931 -
ACS Omega Oct 2023Schistosomiasis, a parasitic disease affecting nearly 250 million individuals globally, poses a significant health challenge. With praziquantel being the sole available...
Schistosomiasis, a parasitic disease affecting nearly 250 million individuals globally, poses a significant health challenge. With praziquantel being the sole available treatment and its limited efficacy in early stage infections, the identification of novel bioactive compounds becomes imperative. This study examines the potential of dehydrodieugenol B () and its methyl ether (), derived from the leaves of the Brazilian plant (Lauraceae), in combatting infections through a preclinical approach. Initially, compound displayed noteworthy in vitro antiparasitic activity with an EC of 31.9 μM, showcasing low toxicity in mammalian cells and an in vivo animal model (). Conversely, compound exhibited no activity. In silico predictions pointed to favorable oral bioavailability and the absence of PAINS similarities. Subsequently, a single oral dose of 400 mg/kg of compound or praziquantel was administered to mice infected with adult (patent infection) or immature parasites (prepatent infection). Remarkably, in prepatent infections, resulted in a significant reduction (approximately 50%) in both worm and egg burden, while praziquantel reduced worm and egg numbers by 30%. The superior efficacy of dehydrodieugenol B () compared to praziquantel in premature infections holds the potential to advance the development of new molecular prototypes for schistosomiasis treatment.
PubMed: 37929107
DOI: 10.1021/acsomega.3c06111 -
Parasites & Vectors Oct 2023In its 'Road map for neglected tropical diseases 2021-2030', the World Health Organization outlined its targets for control and elimination of neglected tropical... (Review)
Review
In its 'Road map for neglected tropical diseases 2021-2030', the World Health Organization outlined its targets for control and elimination of neglected tropical diseases (NTDs) and research needed to achieve them. For many NTDs, this includes research for new treatment options for case management and/or preventive chemotherapy. Our review of small-molecule anti-infective drugs recently approved by a stringent regulatory authority (SRA) or in at least Phase 2 clinical development for regulatory approval showed that this pipeline cannot deliver all new treatments needed. WHO guidelines and country policies show that drugs may be recommended for control and elimination for NTDs for which they are not SRA approved (i.e. for 'off-label' use) if efficacy and safety data for the relevant NTD are considered sufficient by WHO and country authorities. Here, we are providing an overview of clinical research in the past 10 years evaluating the anti-infective efficacy of oral small-molecule drugs for NTD(s) for which they are neither SRA approved, nor included in current WHO strategies nor, considering the research sponsors, likely to be registered with a SRA for that NTD, if found to be effective and safe. No such research has been done for yaws, guinea worm, Trypanosoma brucei gambiense human African trypanosomiasis (HAT), rabies, trachoma, visceral leishmaniasis, mycetoma, T. b. rhodesiense HAT, echinococcosis, taeniasis/cysticercosis or scabies. Oral drugs evaluated include sparfloxacin and acedapsone for leprosy; rifampicin, rifapentin and moxifloxacin for onchocerciasis; imatinib and levamisole for loiasis; itraconazole, fluconazole, ketoconazole, posaconazole, ravuconazole and disulfiram for Chagas disease, doxycycline and rifampicin for lymphatic filariasis; arterolane, piperaquine, artesunate, artemether, lumefantrine and mefloquine for schistosomiasis; ivermectin, tribendimidine, pyrantel, oxantel and nitazoxanide for soil-transmitted helminths including strongyloidiasis; chloroquine, ivermectin, balapiravir, ribavirin, celgosivir, UV-4B, ivermectin and doxycycline for dengue; streptomycin, amoxicillin, clavulanate for Buruli ulcer; fluconazole and isavuconazonium for mycoses; clarithromycin and dapsone for cutaneous leishmaniasis; and tribendimidine, albendazole, mebendazole and nitazoxanide for foodborne trematodiasis. Additional paths to identification of new treatment options are needed. One promising path is exploitation of the worldwide experience with 'off-label' treatment of diseases with insufficient treatment options as pursued by the 'CURE ID' initiative.
Topics: Humans; Ivermectin; Rifampin; Doxycycline; Fluconazole; Off-Label Use; Anti-Infective Agents; Drug Combinations; Neglected Diseases
PubMed: 37907954
DOI: 10.1186/s13071-023-05909-8 -
Life (Basel, Switzerland) Sep 2023The existing treatment strategy for Schistosomiasis centers on praziquantel, a single drug, but its effectiveness is limited due to resistance and lack of preventive...
The existing treatment strategy for Schistosomiasis centers on praziquantel, a single drug, but its effectiveness is limited due to resistance and lack of preventive benefits. Thus, there is an urgent need for novel antischistosomal agents. glutathione S-transferase (GST) is an essential parasite enzyme, with a high potential for targeted drug discovery. In this study, we conducted a screening of compounds possessing antihelminth properties, focusing on their interaction with the glutathione S-transferase (GST) protein. We demonstrated the unique nature of GST in comparison to human GST. Evolutionary analysis indicated its close relationship with other parasitic worms, setting it apart from free-living worms such as . Through an assessment of binding pockets and subsequent protein-ligand docking, we identified Scutiaquinone A and Scutiaquinone B, both naturally derived Perylenequinones, as robust binders to GST. These compounds have exhibited effectiveness against similar parasites and offer promising potential as antischistosomal agents.
PubMed: 37895339
DOI: 10.3390/life13101957 -
Animals : An Open Access Journal From... Oct 2023Aquaculture, a crucial sector of the global food industry, faces a myriad of issues due to parasitic invasions. One such parasite, , which afflicts Korean rockfish in...
Aquaculture, a crucial sector of the global food industry, faces a myriad of issues due to parasitic invasions. One such parasite, , which afflicts Korean rockfish in South Korea, has a significant economic impact. The impending danger of resistance to traditional anthelmintics necessitates the exploration of new antiparasitic candidates. Although the efficacy of salinomycin against aquatic parasites such as ciliates and sporozoans is known, its influence on monogeneans has yet to be studied. Therefore, this study investigated the efficacy and safety of salinomycin for the treatment of infections, presenting the first exploration of salinomycin's therapeutic potential against monogeneans. In vitro examinations revealed a minimum effective concentration of salinomycin of 5 mg/kg, which led to necrosis of the haptor upon dislodging from the gill filaments. The one-time oral administration of the drug at concentrations of 5 mg/kg and 10 mg/kg showed a significant dose-dependent reduction in parasite counts, with no apparent behavioral side effects in Korean rockfish. Biochemical analyses monitored the liver, heart, and kidney enzymes, specifically aspartate transaminase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), and creatine kinase-myocardial band (CK-MB). At both 20 °C and 13 °C, no significant differences were observed in the levels of AST and ALT. However, at 20 °C, alterations in BUN levels were evident on Day 14, a deviation not observed at 13 °C. The CK-MB analysis revealed elevated enzyme levels at both temperatures when compared to the control group, reflecting the similar changes observed in terrestrial animals administered salinomycin. The biochemical data suggest that the oral administration of salinomycin is potentially more favorable at 13 °C than at 20 °C. Although our findings warrant further comprehensive studies, including on the long-term and potential effects on nontarget species and water quality, they also suggest that salinomycin could be considered as an alternative or adjunctive treatment if resistance to the currently used praziquantel against is confirmed.
PubMed: 37893959
DOI: 10.3390/ani13203233 -
Case Reports in Infectious Diseases 2023Vulvar schistosomiasis is a female genital schistosomiasis (FGS), which occurs because of the damage caused by the presence of schistosome ova within the vulva. FGS is...
BACKGROUND
Vulvar schistosomiasis is a female genital schistosomiasis (FGS), which occurs because of the damage caused by the presence of schistosome ova within the vulva. FGS is mostly misdiagnosed as a sexually transmitted infection. There is no reported case of vulvar schistosomiasis from in an immunocompetent or immunocompromised person in Ghanaian medical literature; however, there is a reported case of in an immunocompromised person. This is the first case of vulvar schistosomiasis from infection in an immunocompromised person. This case report discusses the need to consider vulvar schistosomiasis in patients with itchiness of the vulva. . A sixty-nine-year-old married woman presents with a persistent vulvar itch that is unresponsive to treatment. A clinical diagnosis of vulvar lichen planus unresponsive to medical therapy was made. A histopathological diagnosis of vulvar schistosomiasis was, however, made. Ziehl-Neelsen stain revealed the ova of . Symptoms resolved on administration of oral praziquantel.
CONCLUSION
Vulvar schistosomiasis must be considered in clinical history-taking and investigation of signs and symptoms related to itchiness of the vulva. Ziehl-Neelsen staining is a helpful histopathology armamentarium to determine the species of schistosome ova.
PubMed: 37886136
DOI: 10.1155/2023/9913905 -
PLoS Neglected Tropical Diseases Oct 2023Cystic echinococcosis (CE) is caused by the infection of Echinococcus granulosus sensu lato (E. granulosus s.l.), one of the most harmful zoonotic helminths worldwide....
BACKGROUND
Cystic echinococcosis (CE) is caused by the infection of Echinococcus granulosus sensu lato (E. granulosus s.l.), one of the most harmful zoonotic helminths worldwide. Infected dogs are the major source of CE transmission. While praziquantel-based deworming is a main measure employed to control dog infections, its efficacy is at times compromised by the persistent high rate of dog re-infection and the copious discharge of E. granulosus eggs into the environment. Therefore, the dog vaccine is a welcome development, as it offers a substantial reduction in the biomass of E. granulosus. This study aimed to use previous insights into E. granulosus functional genes to further assess the protective efficacy of six recombinant proteins in dogs using a two-time injection vaccination strategy.
METHODS
We expressed and combined recombinant E. granulosus triosephosphate isomerase (rEgTIM) with annexin B3 (rEgANXB3), adenylate kinase 1 (rEgADK1) with Echinococcus protoscolex calcium binding protein 1 (rEgEPC1), and fatty acid-binding protein (rEgFABP) with paramyosin (rEgA31). Beagle dogs received two subcutaneous vaccinations mixed with Quil-A adjuvant, and subsequently orally challenged with protoscoleces two weeks after booster vaccination. All dogs were sacrificed for counting and measuring E. granulosus tapeworms at 28 days post-infection, and the level of serum IgG was detected by ELISA.
RESULTS
Dogs vaccinated with rEgTIM&rEgANXB3, rEgADK1&rEgEPC1, and rEgFABP-EgA31 protein groups exhibited significant protectiveness, with a worm reduction rate of 71%, 57%, and 67%, respectively, compared to the control group (P < 0.05). Additionally, the vaccinated groups exhibited an inhibition of worm growth, as evidenced by a reduction in body length and width (P < 0.05). Furthermore, the level of IgG in the vaccinated dogs was significantly higher than that of the control dogs (P < 0.05).
CONCLUSION
These verified candidates may be promising vaccines for the prevention of E. granulosus infection in dogs following two injections. The rEgTIM&rEgANXB3 co-administrated vaccine underscored the potential for the highest protective efficacy and superior protection stability for controlling E. granulosus infections in dogs.
Topics: Dogs; Animals; Echinococcus granulosus; Echinococcosis; Vaccines, Synthetic; Recombinant Proteins; Dog Diseases; Immunoglobulin G
PubMed: 37871121
DOI: 10.1371/journal.pntd.0011709 -
Cureus Sep 2023Neuroschistosomiasis is a rare manifestation of schistosomal infections presenting with cerebral and spinal cord involvement. We reported a case of a 31-year-old woman...
Neuroschistosomiasis is a rare manifestation of schistosomal infections presenting with cerebral and spinal cord involvement. We reported a case of a 31-year-old woman who presented with a history of headache, dizziness, and nausea. Brain MRI with contrast showed features suggestive of brain lesion with edema, and a serology test for Schistosoma was positive. She was diagnosed with neuroschistosomiasis and treated with intravenous steroids followed by praziquantel resulting in a significant regression of the brain mass. Cerebral neuroschistosomiasis is a rare complication of Schistosoma infection, and clinicians should consider it among the differential diagnosis of unexplained brain lesions.
PubMed: 37854757
DOI: 10.7759/cureus.45418 -
EBioMedicine Nov 2023A controlled human infection model for schistosomiasis (CHI-S) can speed up vaccine development and provides insight into early immune responses following schistosome...
BACKGROUND
A controlled human infection model for schistosomiasis (CHI-S) can speed up vaccine development and provides insight into early immune responses following schistosome exposure. Recently, we established CHI-S model using single-sex male-only Schistosoma mansoni (Sm) cercariae in Schistosoma-naïve individuals. Given important differences in antigenic profile and human immune responses to schistosomes of different sex, we pioneered a single-sex female-only CHI-S model for future use in vaccine development.
METHODS
We exposed 13 healthy, Schistosoma-naïve adult participants to 10 (n = 3) or 20 (n = 10) female cercariae and followed for 20 weeks, receiving treatment with praziquantel (PZQ) 60 mg/kg at week 8 and 12 after exposure.
FINDINGS
The majority (11/13) participants reported rash and/or itch at the site of exposure, 5/13 had transient symptoms of acute schistosomiasis. Exposure to 20 cercariae led to detectable infection, defined as serum circulating anodic antigen levels >1.0 pg/mL, in 6/10 participants. Despite two rounds of PZQ treatment, 4/13 participants showed signs of persistent infection. Additional one- or three-day PZQ treatment (1 × 60 mg/kg and 3 × 60 mg/kg) or artemether did not result in cure, but over time three participants self-cured. Antibody, cellular, and cytokine responses peaked at week 4 post infection, with a mixed Th1, Th2, and regulatory profile. Cellular responses were (most) discriminative for symptoms.
INTERPRETATION
Female-only infections exhibit similar clinical and immunological profiles as male-only infections but are more resistant to PZQ treatment. This limits future use of this model and may have important implications for disease control programs.
FUNDING
European Union's Horizon 2020 (grant no. 81564).
Topics: Adult; Animals; Humans; Male; Female; Schistosomiasis mansoni; Healthy Volunteers; Schistosoma mansoni; Praziquantel; Cytokines; Anthelmintics
PubMed: 37837930
DOI: 10.1016/j.ebiom.2023.104832