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Pathogens (Basel, Switzerland) Sep 2023Preventive chemotherapy with single-dose praziquantel is the WHO-recommended intervention strategy to eliminate schistosomiasis as a public health problem in endemic...
Preventive chemotherapy with single-dose praziquantel is the WHO-recommended intervention strategy to eliminate schistosomiasis as a public health problem in endemic countries. Surveillance of drugs used in mass drug administration (MDA) programs is recommended to evaluate its effectiveness in reducing transmissions. After a decade-long implementation of a school-based MDA program in Rwanda, we conducted efficacy surveillance of single-dose praziquantel MDA against infection. Two weeks before MDA, stool examinations were performed to screen MDA-eligible school children (n = 4998) for infection using the Kato-Katz technique, and 265 (6.5%) children tested positive for the infection. All children received praziquantel and albendazole as preventive chemotherapy through the MDA campaign. Infected children were enrolled and followed for efficacy monitoring, and stool examination was repeated after three weeks post-MDA (n = 188). Before treatment, 173 (92%) had a light infection, and 15 (8%) had a moderate infection intensity. The primary and secondary outcomes were parasitological cure and egg reduction rates at three weeks post-treatment. The overall cure and egg reduction rates for infection were 97.9% (95% CI = 94.6-99.4) and 97.02%, respectively. Among the 173 children with light infection intensity, 170 (98.3%, 95% CI = 95.0-99.6) were cured, and among the 15 children who had moderate infection intensity, 14 (93.3%) were cured. No significant association between cure rate and pre-treatment infection intensity was observed. We conclude that single-dose praziquantel is efficacious against light-to-moderate infection. Preventive chemotherapy with praziquantel effectively reduces schistosome reservoirs and transmission among school-age children.
PubMed: 37764978
DOI: 10.3390/pathogens12091170 -
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 -
Microbiology Spectrum Aug 2023Schistosomiasis is a parasitic disease that afflicts approximately 250 million people worldwide. There is an urgent demand for new antiparasitic agents because...
Schistosomiasis is a parasitic disease that afflicts approximately 250 million people worldwide. There is an urgent demand for new antiparasitic agents because praziquantel, the only drug available for the treatment of schistosomiasis, is not universally effective and may derail current progress toward the WHO goal of eliminating this disease as a public health problem by 2030. Nifuroxazide (NFZ), an oral nitrofuran antibiotic, has recently been explored to be repurposed for parasitic diseases. Here, , , and studies were conducted to evaluate the activity of NFZ on Schistosoma mansoni. The study showed significant antiparasitic activity, with 50% effective concentration (EC) and 90% effective concentration (EC) values of 8.2 to 10.8 and 13.7 to 19.3 μM, respectively. NFZ also affected worm pairing and egg production and induced severe damage to the tegument of schistosomes. , a single oral dose of NFZ (400 mg/kg of body weight) to mice harboring either prepatent or patent S. mansoni infection significantly reduced the total worm burden (~40%). In patent infection, NFZ achieved a high reduction in the number of eggs (~80%), but the drug caused a low reduction in the egg burden of animals with prepatent infection. Finally, results from target fishing methods predicted that serine/threonine kinases could be one of the potential targets for NFZ in S. mansoni. Overall, the present study revealed that NFZ possesses antischistosomal properties, mainly in terms of egg burden reduction in animals with patent S. mansoni infection. The increasing recognition of the burden imposed by helminthiasis, associated with the limited therapeutic arsenal, has led to initiatives and strategies to research and develop new drugs for the treatment of schistosomiasis. One of these strategies is drug repurposing, which considers low-risk compounds with potentially reduced costs and shorter time for development. In this study, nifuroxazide (NFZ) was evaluated for its anti-Schistosoma mansoni potential through , , and studies. , NFZ affected worm pairing and egg production and induced severe damage to the tegument of schistosomes. , a single oral dose of NFZ (400 mg/kg) to mice harboring either prepatent or patent S. mansoni infection significantly reduced the total worm burden and egg production. investigations have identified serine/threonine kinases as a molecular target for NFZ. Collectively, these results implied that NFZ might be a potential therapeutic candidate for the treatment of schistosomiasis.
Topics: Animals; Mice; Schistosomicides; Schistosomiasis mansoni; Schistosoma mansoni; Schistosomiasis; Nitrofurans; Threonine; Serine
PubMed: 37409934
DOI: 10.1128/spectrum.01393-23 -
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 -
PloS One 2023The double burden of malaria and helminthiasis in children poses an obvious public health challenge, particularly in terms of anemia morbidity. While both diseases...
BACKGROUND
The double burden of malaria and helminthiasis in children poses an obvious public health challenge, particularly in terms of anemia morbidity. While both diseases frequently geographically overlap, most studies focus on mono-infection and general prevalence surveys without molecular analysis. The current study investigated the epidemiological determinants of malaria, schistosomiasis, and geohelminthiasis transmission among children in the North Region of Cameroon.
METHODOLOGY
School and pre-school children aged 3-15 year-of-age were enrolled from three communities in March 2021 using a community cross-sectional design. Capillary-blood samples were obtained, and each was examined for malaria parasites using rapid-diagnostic-test (RDT), microscopy, and PCR while hemoglobin level was measured using a hemoglobinometer. Stool samples were analyzed for Schistosoma mansoni, S. guineensis, and soil-transmitted-helminthiasis (STH) infections using the Kato Katz method, and urine samples were assessed for the presence of S. haematobium eggs (including hybrids) using the standard urine filtration technique.
RESULT
A malaria prevalence of 56% (277/495) was recorded by PCR as opposed to 31.5% (156/495) by microscopy and 37.8% (186/495) by RDT. Similarly, schistosomiasis was observed at prevalence levels of up to 13.3% (66/495) overall [S. haematobium (8.7%); S. mansoni (3.8%); mixed Sh/Sm (0.6%); mixed Sh/Sm/Sg (0.2%). Both infections were higher in males and the 3-9 year-of-age groups. A high frequency of PCR reported P. falciparum mono-infection of 81.9% (227/277) and mixed P. falciparum/P. malariae infection of 17.3% (48/277) was observed. Malaria-helminths co-infections were observed at 13.1% (65/495) with marked variation between P. falciparum/S. haematobium (50.8%, 33/65); P. falciparum/S. mansoni (16.9%, 11/65) and P. falciparum/Ascaris (9.2%, 6/65) (χ2 = 17.5, p = 0.00003). Anemia prevalence was 32.9% (163/495), categorically associated with P. falciparum (45.8%, 104/227), Pf/Sh (11.5%, 26/227), and Pf/Sm (3.9%, 9/227) polyparasitism.
CONCLUSION
Polyparasitism with malaria and helminth infections is common in school-aged children despite periodic long-lasting insecticide-treated nets (LLINs) distribution and regular school-based praziquantel (for schistosomiasis) and albendazole (for STH) campaigns. Co-existence of Plasmodium parasites and helminths infections notably Schistosoma species among children may concurrently lead to an increase in Plasmodium infection with an enhanced risk of anemia, highlighting the necessity of an integrated approach for disease control interventions.
Topics: Male; Animals; Humans; Child, Preschool; Child; Adolescent; Cross-Sectional Studies; Cameroon; Seasons; Schistosomiasis; Helminthiasis; Malaria; Malaria, Falciparum; Schistosoma mansoni; Anemia; Prevalence; Feces; Soil
PubMed: 37523402
DOI: 10.1371/journal.pone.0288560 -
Cureus Jul 2023Neurological involvement in schistosomiasis presents a significant and serious complication. While the disease is generally considered treatable during the early stages,...
BACKGROUND
Neurological involvement in schistosomiasis presents a significant and serious complication. While the disease is generally considered treatable during the early stages, the rarity of this condition often leads to delays in diagnosis and treatment. This study aims to report the clinical characteristics of pediatric patients with spinal neuroschistosomiasis (NS) in an endemic area to the disease.
METHODS
A retrospective cross-sectional review was conducted at Althora General Hospital in Ibb, Yemen, from January 2016 to January 2021. The study examined confirmed pediatric cases of spinal NS, analyzing their clinical characteristics, laboratory and radiological data, treatment approaches, and complications.
RESULTS
The study identified 10 cases of spinal NS with a mean age of 10.1± 3.2 years. The majority (90%) were male and from rural areas, all with a history of freshwater exposure, a known risk factor for schistosomiasis. The average time from presentation to treatment was 33.4± 45.6 days (7-150 days). Common symptoms observed in all patients were bladder dysfunction and paresthesia (100%). Intestinal dysfunction was prevalent in 90% of cases, while 80% exhibited limb weakness or inability to walk. The diagnosis was confirmed through cerebrospinal fluid (CSF) serology in 80% of cases, and stool and urine exams yielded positive results in 90% and 30% of cases, respectively. Magnetic Resonance Imaging findings revealed medullary lesions in 50% of cases, cauda equina lesions in 20%, and multiple lesions in 30%. All patients received oral praziquantel and high-dose steroids for at least three days as part of their initial treatment. During the average follow-up period of 5.6±1.7 months, one patient experienced lower extremity paraplegia, while two cases (20%) showed partial improvement with residual deficits including urinary and fecal incontinence. Complete resolution of symptoms was achieved in seven cases (70%).
CONCLUSION
Schistosomiasis should be considered in pediatric patients with myeloradicular manifestations, especially in endemic areas. Early identification can be achieved through history, prompt imaging, and CSF serology. In the absence of immediate test results, expert-guided presumptive therapy should be considered to minimize neurological complications.
PubMed: 37575694
DOI: 10.7759/cureus.41758 -
The American Journal of Tropical... Nov 2023Integration of vertical programs for the control of malaria, schistosomiasis, and soil-transmitted helminthiasis has been recommended to achieve elimination of malaria... (Randomized Controlled Trial)
Randomized Controlled Trial
Integration of vertical programs for the control of malaria, schistosomiasis, and soil-transmitted helminthiasis has been recommended to achieve elimination of malaria and neglected tropical diseases (NTD) by 2030. This qualitative study was conducted within the context of a randomized controlled trial to explore the perceptions and views of parents/caregivers of at-risk children and healthcare providers to determine their acceptability of the integrated malaria-helminth treatment approach. Randomly selected parents/caregivers of children enrolled in the trial, healthcare providers, trial staff, malaria, and NTD program managers were interviewed using purpose-designed topic guides. Transcripts obtained from the interviews were coded and common themes identified using content analysis were triangulated. Fifty-seven study participants comprising 26 parents/caregivers, 10 study children aged ≥ 10 years, 15 trial staff, four healthcare providers, and two managers from the Senegal Ministry of Health were interviewed. Thirty-eight of the participants (66.7%) were males, and their ages ranged from 10 to 65 years. Overall, the integrated malaria-helminth treatment approach was considered acceptable, but the study participants expressed concerns about the taste, smell, and side effects associated with amodiaquine and praziquantel in the combination package. Reluctance to accept the medications was also observed among children aged 10 to 14 years due to peer influence and gender-sensitive cultural beliefs. Addressing concerns about the taste and smell of amodiaquine and praziquantel is needed to optimize the uptake of the integrated treatment program. Also, culturally appropriate strategies need to be put in place to cater for the inclusion of children aged 10 to 14 years in this approach.
Topics: Child; Male; Animals; Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Female; Praziquantel; Amodiaquine; Senegal; Helminthiasis; Helminths; Malaria
PubMed: 37722662
DOI: 10.4269/ajtmh.23-0113 -
PLoS Neglected Tropical Diseases Feb 2024The drug praziquantel (PZQ) has served as the long-standing drug therapy for treatment of infections caused by parasitic flatworms. These encompass diseases caused by... (Review)
Review
The drug praziquantel (PZQ) has served as the long-standing drug therapy for treatment of infections caused by parasitic flatworms. These encompass diseases caused by parasitic blood, lung, and liver flukes, as well as various tapeworm infections. Despite a history of clinical usage spanning over 4 decades, the parasite target of PZQ has long resisted identification. However, a flatworm transient receptor potential ion channel from the melastatin subfamily (TRPMPZQ) was recently identified as a target for PZQ action. Here, recent experimental progress interrogating TRPMPZQ is evaluated, encompassing biochemical, pharmacological, genetic, and comparative phylogenetic data that highlight the properties of this ion channel. Various lines of evidence that support TRPMPZQ being the therapeutic target of PZQ are presented, together with additional priorities for further research into the mechanism of action of this important clinical drug.
Topics: Praziquantel; Anthelmintics; Phylogeny; Transient Receptor Potential Channels
PubMed: 38358948
DOI: 10.1371/journal.pntd.0011929 -
PLoS Neglected Tropical Diseases Aug 2023Echinococcus multilocularis and E. granulosus s.l. are the causative agents of alveolar and cystic echinococcosis, respectively. Drug treatment options for these severe...
Echinococcus multilocularis and E. granulosus s.l. are the causative agents of alveolar and cystic echinococcosis, respectively. Drug treatment options for these severe and neglected diseases are limited to benzimidazoles, which are not always efficacious, and adverse side effects are reported. Thus, novel and improved treatments are needed. In this study, the previously established platform for E. multilocularis in vitro drug assessment was adapted to E. granulosus s.s. In a first step, in vitro culture protocols for E. granulosus s.s. were established. This resulted in the generation of large amounts of E. granulosus s.s. metacestode vesicles as well as germinal layer (GL) cells. In vitro culture of these cells formed metacestode vesicles displaying structural characteristics of metacestode cysts generated in vivo. Next, drug susceptibilities of E. multilocularis and E. granulosus s.s. protoscoleces, metacestode vesicles and GL cells were comparatively assessed employing established assays including (i) metacestode vesicle damage marker release assay, (ii) metacestode vesicle viability assay, (iii) GL cell viability assay, and (iv) protoscolex motility assay. The standard drugs albendazole, buparvaquone, mefloquine, MMV665807, monepantel, niclosamide and nitazoxanide were included. MMV665807, niclosamide and nitazoxanide were active against the parasite in all four assays against both species. MMV665807 and monepantel were significantly more active against E. multilocularis metacestode vesicles, while albendazole and nitazoxanide were significantly more active against E. multilocularis GL cells. Albendazole displayed activity against E. multilocularis GL cells, but no effects were seen in albendazole-treated E. granulosus s.s. GL cells within five days. Treatment of protoscoleces with albendazole and monepantel had no impact on motility. Similar results were observed for both species with praziquantel and its enantiomers against protoscoleces. In conclusion, in vitro culture techniques and drug screening methods previously established for E. multilocularis were successfully implemented for E. granulosus s.s., allowing comparisons of drug efficacy between the two species. This study provides in vitro culture techniques for the reliable generation of E. granulosus s.s. metacestode vesicles and GL cell cultures and describes the validation of standardized in vitro drug screening methods for E. granulosus s.s.
Topics: Animals; Echinococcus granulosus; Albendazole; Niclosamide; Drug Evaluation, Preclinical; Echinococcus multilocularis
PubMed: 37540716
DOI: 10.1371/journal.pntd.0011343 -
ACS Medicinal Chemistry Letters May 2024To investigate the physicochemical properties of anti-schistosomal compounds reported between 2008 and 2023, a simple but extensive literature scrutiny was conducted....
To investigate the physicochemical properties of anti-schistosomal compounds reported between 2008 and 2023, a simple but extensive literature scrutiny was conducted. Keywords were searched in Chemical Abstracts Service (CAS) SciFinder and primary medicinal chemistry and pharmacology literature to locate publications with compounds displaying and/or anti-schistosomal activity. A total of 57 repurposed U.S. Food and Drug Administration (FDA)-approved drugs, hits and their derivatives were manually extracted, curated and compared to known anti-schistosomal oral drugs in view of establishing trends of calculated critical molecular properties. From this analysis, it was determined that more than 65% of the compounds display cLogD > 3 values, whereas oxamniquine, metrifonate and praziquantel (PZQ), previous and currently used oral anti-schistosomal drugs, possess lower cLogD values (≤2.5). Furthermore, the lipophilicity associated with PZQ corresponds to a highly permeable and sparingly soluble compound, characteristics that favor drug absorption and compound penetration in the parasite. These physicochemical properties together with PZQ's anti-schistosomal activity make PZQ an essential medicine for the treatment of schistosomiasis and demonstrate the importance of finding the right balance among potency (e.g., EC < 5 and 0.5 μM), cell permeability (e.g., > 2 × 10 cm/s) and kinetic aqueous solubility (e.g., >10 μM) to provide high-quality hits and/or leads for the discovery of new oral anti-schistosomal therapeutics.
PubMed: 38746890
DOI: 10.1021/acsmedchemlett.4c00026