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1.
PLoS One ; 19(5): e0300384, 2024.
Article in English | MEDLINE | ID: mdl-38758736

ABSTRACT

BACKGROUND: Hundreds of millions of doses of Praziquantel (PZQ) have been administered to persons with and without schistosomiasis living in schistosomiasis endemic settings, through the mass drug administration (MDA) strategy which started in the early 2000s. A recent publication suggested high risk of PZQ-related visual disorders, raising public health concerns. We aim to systematically synthesize evidence on the magnitude of PZQ-related visual disorders. METHODS: We will search PubMed, Google Scholar, CINAHL, SCOPUS, CENTRAL and LILACS from 1977 (when the first human clinical trials on PZQ started) to 31st May 2024, with no language restrictions. The key search terms will include "Praziquantel", "PZQ", "visual disorder", "adverse events", "side effects", "blurry vision" and "visual impairment" together with alternative terms and synonyms. All the countries endemic for schistosomiasis will be included as search terms. We will also search HINARI, Africa Journals Online, Thesis Databases and Preprint Repositories. Where necessary, we will contact expert researchers working in the field of schistosomiasis, UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), pharmaceutical industries, country-specific Food and Drug Authorities (FDAs) and the European Medicines Agency databases. We will search Conference Proceedings and reference lists of relevant studies for additional studies. At least two authors will independently select studies, extract data and assess risk of bias in the included studies. Any disagreements or discrepancies will be resolved through discussion between the reviewers. Heterogeneity will be explored graphically, and statistically using the I2-statistic. We will conduct random-effects meta-analysis when heterogeneity is appreciable, and express dichotomous outcomes (visual adverse events including excessive lacrimation, blurry vision and visual impairments) as risk ratio (RR) or Odds Ratio (OR) with their 95% confidence interval (CI). We will perform subgroup analysis to assess the impact of heterogeneity, and sensitivity analyses to test the robustness of the effect estimates. The overall level of evidence will be assessed using GRADE. EXPECTED OUTCOMES: The present review expects to identify and categorize visual disorders occurring after administration of PZQ, alone or in combination with other drugs. By synthesizing the data from multiple studies, the review aims to present a quantitative assessment of the risk or odds of experiencing a visual disorder in different populations after ingesting PZQ. The review will also generate insights into whether PZQ in combination with other drugs are associated with increased odds of visual disorders and whether the occurrence of visual disorders correlates with dosage or treatment duration. Policymakers, public health experts and stakeholders could rely on the review findings to deliver context-sensitive preventive chemotherapy programs by adjusting drug combinations or dosing schedules to reduce risk of visual adverse effects in populations treated with PZQ. The review aims to identify gaps in the current evidence regarding visual disorders following PZQ administration in schistosomiasis endemic settings which can serve as the basis for future research on important but unanswered questions. DISSEMINATION AND PROTOCOL REGISTRATION: The findings of this study will be disseminated through stakeholder forums, conferences, and peer-review publications. The review protocol has been registered in the International Prospective Register for Systematic Reviews (PROSPERO)- CRD42023417963.


Subject(s)
Mass Drug Administration , Praziquantel , Schistosomiasis , Systematic Reviews as Topic , Vision Disorders , Humans , Schistosomiasis/epidemiology , Schistosomiasis/prevention & control , Schistosomiasis/drug therapy , Praziquantel/therapeutic use , Praziquantel/adverse effects , Praziquantel/administration & dosage , Vision Disorders/epidemiology , Vision Disorders/chemically induced , Meta-Analysis as Topic , Endemic Diseases/prevention & control , Anthelmintics/therapeutic use , Anthelmintics/administration & dosage , Anthelmintics/adverse effects
2.
Parasitology ; 151(5): 523-528, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38571299

ABSTRACT

Dipylidium caninum is a common tapeworm of dogs. Two cases of praziquantel resistance have been described in D. caninum in the United States. No further reports have been published to the authors' knowledge. Here, the case of a dog imported to Switzerland from Spain with a history of chronic excretion of tapeworm proglottids and unresponsiveness to praziquantel treatments is reported. Clinical signs were mild (restlessness, tenesmus, anal pruritus, squashy feces) and flea infestation could be ruled out. Infection with D. caninum was confirmed through morphological and genetic parasite identification. Different subsequently applied anthelmintic compounds and protocols, including epsiprantel, did not confer the desired effects. Proglottid shedding only stopped after oral mebendazole administration of 86.2 mg kg−1 body weight for 5 consecutive days. Clinical signs resolved and the dog remained coproscopically negative during a follow-up period of 10 months after the last treatment. This case represents the first reported apparent praziquantel and epsiprantel resistance in D. caninum in Europe. Treatment was extremely challenging especially due to the limited availability of efficacious alternative compounds.


Subject(s)
Anthelmintics , Cestode Infections , Dog Diseases , Drug Resistance , Praziquantel , Animals , Praziquantel/therapeutic use , Praziquantel/pharmacology , Praziquantel/administration & dosage , Dogs , Dog Diseases/parasitology , Dog Diseases/drug therapy , Anthelmintics/pharmacology , Anthelmintics/therapeutic use , Cestode Infections/drug therapy , Cestode Infections/veterinary , Cestode Infections/parasitology , Switzerland , Cestoda/drug effects , Spain , Feces/parasitology , Male
3.
PLoS Negl Trop Dis ; 18(4): e0012101, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38620032

ABSTRACT

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.


Subject(s)
Anthelmintics , Praziquantel , Rural Population , Schistosoma haematobium , Schistosomiasis haematobia , Nigeria/epidemiology , Humans , Praziquantel/administration & dosage , Praziquantel/therapeutic use , Child , Schistosomiasis haematobia/drug therapy , Schistosomiasis haematobia/epidemiology , Animals , Female , Male , Adolescent , Schistosoma haematobium/drug effects , Anthelmintics/administration & dosage , Anthelmintics/therapeutic use , Adult , Young Adult , Prevalence , Snails/parasitology , Child, Preschool , Middle Aged , Endemic Diseases , Parasite Egg Count
4.
Lancet Infect Dis ; 22(1): 136-149, 2022 01.
Article in English | MEDLINE | ID: mdl-34863336

ABSTRACT

BACKGROUND: Over the past 20 years, schistosomiasis control has been scaled up. Preventive chemotherapy with praziquantel is the main intervention. We aimed to assess the effect of preventive chemotherapy on schistosomiasis prevalence in sub-Saharan Africa, comparing 2000-10 with 2011-14 and 2015-19. METHODS: In this spatiotemporal modelling study, we analysed survey data from school-aged children (aged 5-14 years) in 44 countries across sub-Saharan Africa. The data were extracted from the Global Neglected Tropical Diseases database and augmented by 2018 and 2019 survey data obtained from disease control programmes. Bayesian geostatistical models were fitted to Schistosoma haematobium and Schistosoma mansoni survey data. The models included data on climatic predictors obtained from satellites and other open-source environmental databases and socioeconomic predictors obtained from various household surveys. Temporal changes in Schistosoma species prevalence were estimated by a categorical variable with values corresponding to the three time periods (2000-10, 2011-14, and 2015-19) during which preventive chemotherapy interventions were scaled up. FINDINGS: We identified 781 references with relevant geolocated schistosomiasis survey data for 2000-19. There were 19 166 unique survey locations for S haematobium and 23 861 for S mansoni, of which 77% (14 757 locations for S haematobium and 18 372 locations for S mansoni) corresponded to 2011-19. Schistosomiasis prevalence among school-aged children in sub-Saharan Africa decreased from 23·0% (95% Bayesian credible interval 22·1-24·1) in 2000-10 to 9·6% (9·1-10·2) in 2015-19, an overall reduction of 58·3%. The reduction of S haematobium was 67·9% (64·6-71·1) and that of S mansoni 53·6% (45·2-58·3) when comparing 2000-10 with 2015-19. INTERPRETATION: Our model-based estimates suggest that schistosomiasis prevalence in sub-Saharan Africa has decreased considerably, most likely explained by the scale-up of preventive chemotherapy. There is a need to consolidate gains in the control of schistosomiasis by means of preventive chemotherapy, coupled with other interventions to interrupt disease transmission. FUNDING: European Research Council and WHO.


Subject(s)
Anthelmintics/therapeutic use , Praziquantel/therapeutic use , Schistosoma haematobium/drug effects , Schistosoma mansoni/drug effects , Schistosomiasis/drug therapy , Spatio-Temporal Analysis , Adolescent , Africa South of the Sahara/epidemiology , Animals , Chemoprevention , Child , Child, Preschool , Cross-Sectional Studies , Databases, Factual , Humans , Praziquantel/administration & dosage , Prevalence , Schistosomiasis/classification , Schistosomiasis/epidemiology , Schools
5.
Front Immunol ; 12: 748387, 2021.
Article in English | MEDLINE | ID: mdl-34956183

ABSTRACT

Beyond transient control of the infection, additional benefits of mass drug administration of praziquantel in endemic communities have been suggested in communities but not mechanistically investigated experimentally. The present study sought to evaluate the additional and hitherto unreported benefits of repeated mass drug administration of praziquantel. We used a tractable mouse model of Schistosoma mansoni infection to assess the effects of repeated infection-treatment cycles on the host susceptibility to reinfection. Parasitaemia was assessed by quantification of Schistosoma egg burden in liver tissues and morbidity was followed up by histological observation of liver lesions by microscopy and using biochemical measurement of liver transaminases. Immune responses were further determined by serum probing of schistosoma-specific antibodies, cytokines and quantification of liver cellular and soluble mediator responses by flow cytometry and ELISA, respectively. At similar ages and comparable gender distribution, groups of mice undergoing higher number of infections treatment cycles over a longer period, remained susceptible to reinfection by the parasite, as judged by the presence of eggs and the associated increasing pathology in the liver tissues. However, notably, there was a clear and significantly higher propensity to lower egg burden upon reinfection when compared to counterparts undergoing a lower number of infection-treatment cycles. This relative reduction of susceptibility to infection was paralleled by a more robust humoral response against parasite antigens, elevated serum IL-4 and liver cytokines. Of note, praziquantel treatment of infected mice left them at a higher baseline of serum IL-4, IgE and liver cytokines but lower CD4+ T cell -derived cytokines when compared to infected non-treated mice supporting an immunological treatment-induced advantage of previously infected mice over naïve mice and infected/not treated mice. Notably, repeated infection-treatment cycles did not preclude the infection-driven aggravation of collagen deposition in the livers over time and was corroborated by a more robust local production of inflammatory cytokines in the most exposed livers. Taken together, our data reveal that treatment of S. mansoni-infected hosts with praziquantel rewires the immune system to a conformation less permissive to subsequent reinfection in mice. Provided the data are translatable from mouse to human, our findings may provide mechanistic support to the potential benefits of more frequent MDAs in high transmission areas to allow rapid acquisition of protective immunity against reinfection.


Subject(s)
Anthelmintics/pharmacology , Praziquantel/pharmacology , Schistosoma mansoni/drug effects , Schistosomiasis mansoni/drug therapy , Administration, Oral , Animals , Anthelmintics/administration & dosage , Flow Cytometry , Mice , Mice, Inbred Strains , Parasitic Sensitivity Tests , Praziquantel/administration & dosage , Schistosoma mansoni/immunology , Schistosomiasis mansoni/immunology , Schistosomiasis mansoni/parasitology
6.
S Afr Med J ; 111(11): 1050-1054, 2021 11 05.
Article in English | MEDLINE | ID: mdl-34949267

ABSTRACT

A previously healthy 10-year-old girl, living in a sheep-farming community in South Africa with exposure to dogs, presented to her local hospital with generalised tonic-clonic seizures. The initial clinical assessment and laboratory work-up were unremarkable. When she presented with further seizures 6 months later, attempts to arrange neuroimaging and specialist assessment were unsuccessful owing to restrictions on routine healthcare services during the SARS-CoV-2 nationwide lockdown. Subsequently, 11 months after her first presentation, she developed focal neurological signs suggestive of raised intracranial pressure. A brain computed tomography scan revealed a left-sided cerebral cyst and imminent tonsillar herniation. An emergency burr-hole procedure was performed to relieve the raised intracranial pressure, followed by definitive neurosurgical excision of cysts. Hydatid protoscolices and hooklets were seen on microscopy of cyst fluid, and treatment with albendazole and praziquantel was initiated. While her infection was treated successfully, long-term sequelae including permanent blindness and hemiparesis could potentially have been prevented with early neuroimaging and surgical intervention.


Subject(s)
Anticestodal Agents/administration & dosage , Brain Diseases/diagnosis , COVID-19 , Echinococcosis/diagnosis , Albendazole/administration & dosage , Brain Diseases/drug therapy , Brain Diseases/parasitology , Child , Delayed Diagnosis , Echinococcosis/drug therapy , Female , Humans , Intracranial Hypertension/parasitology , Praziquantel/administration & dosage , Seizures/parasitology , South Africa , Tomography, X-Ray Computed
7.
PLoS One ; 16(12): e0260722, 2021.
Article in English | MEDLINE | ID: mdl-34932602

ABSTRACT

INTRODUCTION: The Geshiyaro project aims to break transmission of soil-transmitted helminths and schistosomiasis in the Wolaita Zone of Ethiopia through a combination of two interventions: behavior change communication (BCC) for increased water, sanitation and hygiene (WaSH) infrastructure use alongside preventive chemotherapy (PC) using albendazole (ALB) and praziquantel (PZQ), targeted to reach 90% treatment coverage. Coverage evaluation surveys (CES) were conducted post-treatment, and the resultant survey coverage was compared to reported administrative coverage. This provided a secondary confirmation of the Geshiyaro project coverages, and is used to monitor the success of each Mass Drug Administration (MDA) round. METHODS: A community-based cross-sectional study was conducted in 13 woredas (districts) of the Wolaita Zone. All eligible individuals from the selected households were invited for an interview. The study design, sample size, analysis and report writing were conducted according to the World Health Organization (WHO) CES guidelines for PC. RESULTS: The study interviewed a total of 3,568 households and 18,875 individuals across 13 woredas in the Wolaita Zone. Overall, the survey coverage across all studied woredas was 81.5% (95% CI; 80.9-82.0%) for both ALB and PZQ. Reported administrative coverage across all studied woredas was higher than survey coverage, 92.7% and 91.2% for ALB and PZQ, respectively. A significant portion of individuals (17.6%) were not offered PC. The predominant reason for not achieving the target coverage of 90% was beneficiary absenteeism during MDA (6.6% ALB, 6.8% PZQ), followed by drug distributors failing to reach all households (4.7% ALB, 4.8% PZQ), and beneficiaries not informed of the program (1.3% ALB, 1.7% PZQ). CONCLUSION: Programmatic actions will need to be taken during the next MDA campaign to achieve the targeted Geshiyaro project coverage threshold across data collection and program engagement. Adequate training and supervision on recording and reporting administrative coverage should be provided, alongside improved social mobilization of treated communities to increase participation, and strengthened institutional partnerships and communication.


Subject(s)
Albendazole/administration & dosage , Anthelmintics/administration & dosage , Chemoprevention/methods , Helminthiasis/prevention & control , Praziquantel/administration & dosage , Schistosomiasis/prevention & control , Adolescent , Adult , Animals , Child , Child, Preschool , Cross-Sectional Studies , Ethiopia/epidemiology , Family Characteristics , Female , Helminthiasis/epidemiology , Helminthiasis/parasitology , Helminthiasis/transmission , Humans , Hygiene/education , Infant , Male , Mass Drug Administration/statistics & numerical data , Middle Aged , Prevalence , Sanitation/methods , Schistosomiasis/epidemiology , Schistosomiasis/parasitology , Schistosomiasis/transmission , Soil/parasitology , Surveys and Questionnaires
8.
PLoS Negl Trop Dis ; 15(11): e0009981, 2021 11.
Article in English | MEDLINE | ID: mdl-34793443

ABSTRACT

Extracellular Vesicles (EVs) are an integral component of cellular/organismal communication and have been found in the excreted/secreted (ES) products of both protozoan and metazoan parasites. Within the blood fluke schistosomes, EVs have been isolated from egg, schistosomula, and adult lifecycle stages. However, the role(s) that EVs have in shaping aspects of parasite biology and/or manipulating host interactions is poorly defined. Herein, we characterise the most abundant EV-enriched protein in Schistosoma mansoni tissue-migrating schistosomula (Schistosoma mansoni Larval Extracellular Vesicle protein 1 (SmLEV1)). Comparative sequence analysis demonstrates that lev1 orthologs are found in all published Schistosoma genomes, yet homologs are not found outside of the Schistosomatidae. Lifecycle expression analyses collectively reveal that smlev1 transcription peaks in cercariae, is male biased in adults, and is processed by alternative splicing in intra-mammalian lifecycle stages. Immunohistochemistry of cercariae using a polyclonal anti-recombinant SmLEV1 antiserum localises this protein to the pre-acetabular gland, with some disperse localisation to the surface of the parasite. S. mansoni-infected Ugandan fishermen exhibit a strong IgG1 response against SmLEV1 (dropping significantly after praziquantel treatment), with 11% of the cohort exhibiting an IgE response and minimal levels of detectable antigen-specific IgG4. Furthermore, mice vaccinated with rSmLEV1 show a slightly reduced parasite burden upon challenge infection and significantly reduced granuloma volumes, compared with control animals. Collectively, these results describe SmLEV1 as a Schistosomatidae-specific, EV-enriched immunogen. Further investigations are now necessary to uncover the full extent of SmLEV1's role in shaping schistosome EV function and definitive host relationships.


Subject(s)
Cercaria/immunology , Extracellular Vesicles/immunology , Helminth Proteins/immunology , Schistosoma mansoni/immunology , Schistosomiasis mansoni/parasitology , Adolescent , Adult , Amino Acid Sequence , Animals , Anthelmintics/administration & dosage , Antibodies, Helminth/immunology , Cercaria/genetics , Cercaria/growth & development , Child , Cohort Studies , Extracellular Vesicles/genetics , Female , Helminth Proteins/administration & dosage , Helminth Proteins/chemistry , Helminth Proteins/genetics , Humans , Immunogenicity, Vaccine , Immunoglobulin E/immunology , Immunoglobulin G/immunology , Male , Mice , Middle Aged , Praziquantel/administration & dosage , Schistosoma mansoni/chemistry , Schistosoma mansoni/genetics , Schistosoma mansoni/growth & development , Schistosomiasis mansoni/drug therapy , Schistosomiasis mansoni/immunology , Sequence Alignment , Vaccines/administration & dosage , Vaccines/genetics , Vaccines/immunology , Young Adult
9.
Am J Trop Med Hyg ; 106(1): 268-274, 2021 10 25.
Article in English | MEDLINE | ID: mdl-34695783

ABSTRACT

Coverage surveys for mass drug administration (MDA) rely on respondent recall and often permit proxy responses, whereby another household member is allowed to respond on behalf of an absent individual. In this secondary analysis of coverage surveys in Malawi, Burkina Faso, and Uganda, we explore the characteristics of individuals who require proxy responses and quantify the association between proxy responses and reported drug coverage. The adjusted logistic regression model found that men 11-39 years and women 11-18 years who were eligible for MDA had greater odds of requiring a proxy response compared with ineligible men and women in the same age groups. A hierarchical multivariable analysis found that proxy responses had 1.70 times the odds of reporting ingestion of MDA drugs compared with first-person responses, controlling for age and sex (95% CI: 1.17, 2.46). This finding is surprising, given that individuals absent during a coverage survey may also have been absent during the MDA, and suggests that proxy responses may be leading to an inflation of survey estimates of drug coverage. This study highlights the possibility for recall bias in proxy responses to MDA coverage; however, excluding absent individuals from coverage surveys would introduce a new bias. Further research is necessary to determine the best method for obtaining information on drug coverage when individuals are absent.


Subject(s)
Anthelmintics/administration & dosage , Anti-Bacterial Agents/administration & dosage , Antiparasitic Agents/administration & dosage , Mass Drug Administration/statistics & numerical data , Proxy , Adolescent , Adult , Albendazole/administration & dosage , Azithromycin/administration & dosage , Burkina Faso , Child , Demography , Female , Humans , Ivermectin/administration & dosage , Logistic Models , Malawi , Male , Mass Drug Administration/trends , Mental Recall , Praziquantel/administration & dosage , Uganda , Young Adult
10.
Am J Trop Med Hyg ; 106(1): 219-221, 2021 10 25.
Article in English | MEDLINE | ID: mdl-34695801

ABSTRACT

Cestodes of Bertiella genus are parasites of nonhuman primates. We describe a rare case of human bertiellosis in South Africa: a 3-year-old girl with a 1-year history of rectal proglottid discharge and intermittent abdominal pain. After repeated failure with benzimidazole antihelminthic treatment, praziquantel proved successful.


Subject(s)
Cestoda/isolation & purification , Cestode Infections/diagnosis , Animals , Anthelmintics/administration & dosage , Cestoda/classification , Cestode Infections/drug therapy , Cestode Infections/parasitology , Child, Preschool , Feces/parasitology , Female , Humans , Praziquantel/administration & dosage , South Africa
11.
PLoS Negl Trop Dis ; 15(9): e0009706, 2021 09.
Article in English | MEDLINE | ID: mdl-34473691

ABSTRACT

BACKGROUND: Mekong schistosomiasis is a parasitic disease caused by the blood-dwelling fluke Schistosoma mekongi. This disease contributes to human morbidity and mortality in the Mekong region, posing a public health threat to people in the area. Currently, praziquantel (PZQ) is the drug of choice for the treatment of Mekong schistosomiasis. However, the molecular mechanisms of PZQ action remain unclear, and Schistosoma PZQ resistance has been reported occasionally. Through this research, we aimed to use a metabolomic approach to identify the potentially altered metabolic pathways in S. mekongi associated with PZQ treatment. METHODOLOGY/PRINCIPAL FINDINGS: Adult stage S. mekongi were treated with 0, 20, 40, or 100 µg/mL PZQ in vitro. After an hour of exposure to PZQ, schistosome metabolites were extracted and studied with mass spectrometry. The metabolomic data for the treatment groups were analyzed with the XCMS online platform and compared with data for the no treatment group. After low, medium (IC50), and high doses of PZQ, we found changes in 1,007 metabolites, of which phosphatidylserine and anandamide were the major differential metabolites by multivariate and pairwise analysis. In the pathway analysis, arachidonic acid metabolism was found to be altered following PZQ treatment, indicating that this pathway may be affected by the drug and potentially considered as a novel target for anti-schistosomiasis drug development. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that arachidonic acid metabolism is a possible target in the parasiticidal effects of PZQ against S. mekongi. Identifying potential targets of the effective drug PZQ provides an interesting viewpoint for the discovery and development of new agents that could enhance the prevention and treatment of schistosomiasis.


Subject(s)
Anthelmintics/administration & dosage , Arachidonic Acid/metabolism , Praziquantel/administration & dosage , Schistosoma/drug effects , Schistosoma/metabolism , Schistosomiasis/drug therapy , Animals , Drug Resistance , Female , Humans , Life Cycle Stages/drug effects , Mice , Mice, Inbred ICR , Praziquantel/pharmacology , Schistosoma/genetics , Schistosoma/growth & development , Schistosomiasis/parasitology
12.
Sci Rep ; 11(1): 17955, 2021 09 09.
Article in English | MEDLINE | ID: mdl-34504222

ABSTRACT

Praziquantel pharmacokinetics studies in schistosomiasis infected children are scarce partly due to the challenges/complexity of intensive blood sampling in the target population. This study was aimed to investigate the optimal single sampling time-point for monitoring praziquantel exposure. This was intensive pharmacokinetic study conducted among 32 Schistosoma mansoni infected children treated with an oral standard single-dose 40 mg/kg praziquantel. Plasma samples were collected at 0, 1, 2, 4, 6 and 8 h post-praziquantel administration. Quantification of praziquantel and its enantiomers (R- and S-praziquantel) concentrations was done by Liquid chromatography-tandem mass spectrometer (LC-MS/MS). The correlation between area under the plasma concentration-time curve from 0 to 8 h (AUC8) and plasma concentrations at each specific sampling time-point was determined by Pearson's correlation coefficient (r2). The median age (range) of the study population was 12.5 years (10-17). The study participants were 17 males and 15 females. Both total praziquantel and its enantiomers (R- and S-praziquantel) displayed a wide inter-individual pharmacokinetic variability. Regression analysis indicated that, plasma concentrations collected at 4 h post-dose had a significantly highest correlation with the AUC8 for both total praziquantel (r2 = 0.81, p < 0.001) and S-praziquantel (r2 = 0.84, p < 0.001) than any other sampling time-point; while for R-praziquantel, plasma concentrations collected at 6 h sampling time-point had a significantly highest correlation with the AUC8 (r2 = 0.79, p < 0.001) than any other sampling time-point. Four hours sampling time-point post-praziquantel administration is ideal optimal single sampling time-point for therapeutic monitoring of total praziquantel exposure while 6 h sampling time-point is suitable for monitoring of a pharmacologically active R-praziquantel enantiomer.


Subject(s)
Anthelmintics/administration & dosage , Anthelmintics/pharmacokinetics , Drug Monitoring/methods , Praziquantel/administration & dosage , Praziquantel/pharmacokinetics , Schistosoma mansoni/isolation & purification , Schistosomiasis mansoni/drug therapy , Administration, Oral , Adolescent , Animals , Anthelmintics/blood , Biological Availability , Blood Specimen Collection/methods , Child , Chromatography, Liquid , Feces/parasitology , Female , Humans , Isomerism , Male , Praziquantel/blood , Schistosomiasis mansoni/blood , Schistosomiasis mansoni/parasitology , Tandem Mass Spectrometry
13.
PLoS Negl Trop Dis ; 15(9): e0009757, 2021 09.
Article in English | MEDLINE | ID: mdl-34547034

ABSTRACT

Intestinal schistosomiasis is a neglected tropical disease, causing morbidity and mortality in tropical and subtropical countries. Despite the frequent implementation of mass drug administration with praziquantel, the reinfection with Schistosoma mansoni is still common in Yemen. In addition, there is a scarcity of information on the impact of S. mansoni on nutritional status and anemia among schoolchildren. The present study aimed to determine prevalence and risk factors of intestinal schistosomiasis and investigate its impact on nutritional status and anemia among schoolchildren in Sana'a Governorate, Yemen. It was conducted in 2018 on 445 schoolchildren aged 5-15 years. Biodata, socio-economic, demographic, behavioral and environmental data were collected using a standard questionnaire. S. mansoni was identified and quantified by microscopic examination of Kato-Katz fecal smear. Hemoglobin concentration and anthropometric measurements were estimated using standard methods. The prevalence of S. mansoni was higher in Al-Haimah Al-Dakheliah (33.9%) than Bani Mater (1.4%). Household without tap water (Adjusted Odds Ratio (AOR) = 2.9, 95% Confidence interval (CI): 1.12, 7.55, P = 0.028) was the independent risk factor of the infection. The prevalence of wasting and stunting was 25.0% (95%CI: 21.2%, 29.2%) and 45.8% (95%CI: 41.2%, 50.5%), respectively. The prevalence of underweight among schoolchildren aged 5-10 years was 27.3% (95%CI: 21.9%, 33.4%). The prevalence of anemia was 31.7% (95%CI: 27.5%, 36.2%) with 0.5%, 21.1% and 10.1% being severe, moderate and mild anemia, respectively. S. mansoni (AOR = 4.1, 95%CI: 2.16, 7.84, P < 0.001) and early adolescence (AOR = 6.8, 95%CI: 4.26, 10.82, P < 0.001) were independent predictors of stunting among schoolchildren. The early adolescent schoolchildren (AOR = 3.1, 95%CI: 1.86, 4.97, P < 0.001) and children from families with low (AOR = 2.1, 95%CI: 1.01, 4.15, P = 0.046) or moderate wealth (AOR = 2.3, 95%CI: 1.11, 4.77, P = 0.026) were significantly more wasted. Early adolescence (AOR = 1.8, 95%CI:1.14, 2.78, P = 0.011), female (AOR = 1.6, 95%CI: 1.03, 2.43, P = 0.038) and Al-Haimah Al-Dakheliah District (AOR = 3.4, 95%CI: 1.20, 9.55, P = 0.021) were independent risk factors for anemia. The study findings indicate highly focal prevalence of schistosomiasis in Sana'a Governorate with a public health significance that varies from low to high risk. Approximately half of schoolchildren were stunted, which was associated with S. mansoni infection and early adolescence. One quarter of schoolchildren were wasted with early adolescent schoolchildren and children from poor families being at high risk of wasting. Anemia was a moderate public health threat affecting the female and the early adolescent schoolchildren. The study suggests the implementation of control measures to combat schistosomiasis and integrated diseases control programmes to improve the health status of schoolchildren in Sana'a Governorate.


Subject(s)
Nutritional Status , Schistosomiasis mansoni/diagnosis , Schistosomiasis mansoni/epidemiology , Adolescent , Anthelmintics/administration & dosage , Anthelmintics/therapeutic use , Child , Feces/parasitology , Female , Growth Disorders/epidemiology , Humans , Male , Mass Drug Administration , Praziquantel/administration & dosage , Praziquantel/therapeutic use , Prevalence , Risk Factors , Yemen/epidemiology
14.
Washington, D.C; PAHO; Sept. 7, 2021. 60 p.
Monography in English | BIGG - GRADE guidelines | ID: biblio-1291054

ABSTRACT

The larval stage of the parasite Taenia solium can encyst in the central nervous system causing neurocysticercosis, which is the main cause of acquired epilepsy in the countries in which the parasite is endemic. Endemic areas are those with the presence (or likely presence) of the full life cycle of Taenia solium. The parasite is most prevalent in poor and vulnerable communities in which pigs roam free, open defecation is practiced, basic sanitation is deficient, and health education is absent or limited. Several tools are available for the control of Taenia solium. Preventive chemotherapy for Taenia solium taeniasis, which is directed at the adult tapeworm, is one of them. Other tools focus on pig management, pig vaccination and treatment, sanitation and hygiene, and community education. Three potential drugs­niclosamide, praziquantel, and albendazole­have been considered for use for preventive chemotherapy in Taenia solium taeniasis control programs through mass drug administration or targeted chemotherapy. In this Guideline, we provide recommendations for preventive chemotherapy in Taenia solium-endemic areas using niclosamide, praziquantel, or albendazole, including at which dose and in which population groups. The development of this Guideline is based on the latest standard World Health Organization methods for guideline development, including the use of systematic search strategies, synthesis, quality assessment of the available evidence to support the recommendations, and participation of experts and stakeholders in the Guideline Development Group and External Review Group. The recommendations are intended for a wide audience, including policymakers and their expert advisers, and technical and program staff at governmental institutions and organizations involved in the planning, implementation, monitoring, and evaluation of preventive chemotherapy programs for the control of Taenia solium.


Subject(s)
Humans , Female , Pregnancy , Child , Adolescent , Taeniasis/drug therapy , Taenia solium/drug effects , Drug Therapy , Praziquantel/administration & dosage , Taeniasis/complications , Albendazole/administration & dosage , Niclosamide/analogs & derivatives
15.
PLoS Negl Trop Dis ; 15(8): e0009578, 2021 08.
Article in English | MEDLINE | ID: mdl-34351907

ABSTRACT

Elimination of schistosomiasis as a public health problem among all disease-endemic countries in 2030 is an ambitious goal. Recent achievements resulting from mass drug administration (MDA) with praziquantel is promising but may need to be complemented with also other means. Schistosomiasis was highly prevalent in China before the initiation of the national schistosomiasis control program in the mid-1950s, and, at that time, the country bore the world's highest burden of schistosomiasis. The concerted control efforts, upheld without interruption for more than a half century, have resulted in elimination of the disease as a public health problem in China as of 2015. Here, we describe the current status of schistosomiasis in China, analyze the potential challenges affecting schistosomiasis elimination, and propose the future research needs and priorities for the country, aiming to provide more universal insights into the structures needed for a global schistosomiasis elimination encompassing also other endemic regions.


Subject(s)
Disease Eradication , Schistosomiasis/epidemiology , Schistosomiasis/prevention & control , Animals , China/epidemiology , Humans , Mass Drug Administration , Praziquantel/administration & dosage , Public Health , Snails
16.
J Fish Dis ; 44(11): 1819-1829, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34339060

ABSTRACT

Parasite infections in fish require constant surveillance and strategies for efficient treatments which guarantee the fish health, their sale value and the non-propagation of pathogens in new environments. Fish treatments based on nanotechnology become of increasing interest since nanoparticles have been shown as efficient materials for optimizing administration of bioactives. In this study a chitosan derivative, alginate and praziquantel conjugated nanobioparticle of effective action for oral treatment of digenetic trematodes in highly infected Corydoras schwartzi was evaluated in terms of histological and hematological safety. The inherent absence of alterations in intestinal tissue and the reversible blood cells counting during a period up to 35 days showed the safety of the drug delivery nanobioparticles, which thus represent a promising strategy for effective applications in pathogens treatments by oral administration.


Subject(s)
Catfishes/parasitology , Fish Diseases/drug therapy , Nanoparticles , Praziquantel/administration & dosage , Trematode Infections/veterinary , Administration, Oral , Alginates , Animals , Chitosan , Drug Carriers , Fish Diseases/parasitology , Intestines/drug effects , Intestines/pathology , Trematoda/drug effects , Trematode Infections/drug therapy
17.
PLoS Negl Trop Dis ; 15(7): e0009443, 2021 07.
Article in English | MEDLINE | ID: mdl-34237061

ABSTRACT

Echinococcosis is a serious zoonotic parasitic disease transmitted from canines to humans and livestock. Periodic deworming is recommended by the WHO/OIE as a highly effective measure against echinococcosis. However, manual deworming involves significant challenges, particularly in remote areas with scarce resources. The insufficient awareness delivering praziquantel (PZQ) baits for dogs leads to low compliance rate. The aim of this study was therefore to develop a novel smart collar for dogs to address these challenges. We developed a smart Internet of Things (IoT)-based deworming collar which can deliver PZQ baits for dogs automatically, regularly, quantitatively with predominant characteristics of being waterproof, anti-collision, cold-proof and long life battery. Its performance was tested in two remote locations on the Tibetan Plateau. A cross-sectional survey was conducted to evaluate the compliance of the dog owners. Further, a randomized controlled study was performed to evaluate the difference between smart-collar deworming and manual deworming. The collar's effectiveness was further assessed on the basis of Generalized Estimation Equations (GEE). The testing and evaluation was done for 10 smart deworming collars in factory laboratory, 18 collars attached for 18 dogs in Seni district, Tibet Autonomous Region, China, and 523 collars attached for 523 dogs in Hezuo city, Gansu province, China. The anti-collision, waterproof, and coldproof proportion of the smart collars were 100.0%, 99.5%, and 100.0%, respectively. When compared to manual deworming, the dogs' risk of infection with Echinococcus on smart-collar deworming is down to 0.182 times (95% CI: 0.049, 0.684) in Seni district and 0.355 (95%CI: 0.178, 0.706) in Hezuo city, the smart collar has a significant protective effect. The owners' overall compliance rate to attach the smart collars for their dogs was 89%. The smart deworming collar could effectively reduce the dogs' risk of infection with Echinococcus in dogs, significantly increase the deworming frequency and coverage and rapidly remove worm biomass in dogs. Thus, it may be a promising alternative to manual deworming, particularly in remote areas on the Tibetan Plateau.


Subject(s)
Anthelmintics/administration & dosage , Dog Diseases/drug therapy , Echinococcosis/veterinary , Praziquantel/administration & dosage , Animals , China , Cross-Sectional Studies , Dog Diseases/epidemiology , Dog Diseases/parasitology , Dogs , Echinococcosis/drug therapy , Echinococcosis/epidemiology , Echinococcosis/parasitology , Echinococcus/drug effects , Echinococcus/physiology , Female , Male , Tibet/epidemiology
18.
PLoS Negl Trop Dis ; 15(7): e0009490, 2021 07.
Article in English | MEDLINE | ID: mdl-34280206

ABSTRACT

Treatment and control of schistosomiasis depends on a single drug, praziquantel, but this is not ideal for several reasons including lack of potency against the juvenile stage of the parasite, dose size, and risk of resistance. We have optimised the properties of a series of compounds we discovered through high throughput screening and have designed candidates for clinical development. The best compounds demonstrate clearance of both juvenile and adult S. mansoni worms in a mouse model of infection from a single oral dose of < 10 mg/kg. Several compounds in the series are predicted to treat schistosomiasis in humans across a range of species with a single oral dose of less than 5 mg/kg.


Subject(s)
Schistosoma mansoni/drug effects , Schistosoma mansoni/growth & development , Schistosomiasis mansoni/drug therapy , Schistosomicides/administration & dosage , Schistosomicides/chemistry , Animals , Drug Administration Schedule , Drug Discovery , Female , Humans , Male , Mice , Praziquantel/administration & dosage , Praziquantel/chemistry , Schistosoma mansoni/physiology , Schistosomiasis mansoni/parasitology , Treatment Outcome
19.
Pan Afr Med J ; 39: 2, 2021.
Article in French | MEDLINE | ID: mdl-34178230

ABSTRACT

Genital schistosomiasis is mainly located in the neck of the uterus and the vagina, less frequently on the vulva, the fallopian tubes and ovaries and rarely in the body of the uterus. We here report the case of a 10-year-old girl admitted with a swelling on the vulva in whom histological examination showed cutaneous schistosomiasis due to Schistosoma haematobium. Outcome was favorable with a single 40 mg/kg mg dose of praziquantel, with tumor regression.


Subject(s)
Praziquantel/administration & dosage , Schistosomiasis haematobia/diagnosis , Vulvar Diseases/diagnosis , Animals , Anthelmintics/administration & dosage , Child , Female , Humans , Mali , Schistosoma haematobium/isolation & purification , Schistosomiasis haematobia/drug therapy , Vulvar Diseases/drug therapy , Vulvar Diseases/parasitology
20.
Trop Biomed ; 38(2): 205-213, 2021 Jun 01.
Article in English | MEDLINE | ID: mdl-34172712

ABSTRACT

Schistosomiasis is the second most common parasitic disease post Malaria around the world. Praziquantel (PZQ) is known as the most efficient anti- schistosomal drug but has no anti-fibrotic effect. Metformin (Met) is a well-known drug for type 2 diabetes. This study aimed to evaluate the role of Met as anti-schistosomal and anti-fibrotic agents alone or in combination with PZQ treatment. Forty male CD1 mice were divided into four groups (n=10 mice) as following; the first group (Gp1) was served as a negative control. Gp2, Gp3, Gp4, and Gp5 were infected with (60-80) S. mansoni cercariae. After a month of infection, Gp3 was administered orally with PZQ (500 mg/Kg) for 2 consecutive days. Gp4 was administered orally with Met (150 mg/Kg) for 15 consecutive days, and Gp5 was orally administered with PZQ followed by Met for 15 consecutive days at the same doses as in Gp 3 and 4. The results showed that PZQ had potent worms and egg reduction in liver and intestine tissues with no anti-fibrotic effect of the granuloma formation. However, Met or PZQ/Met treatment postinfection led to a reduction in egg count in both liver and intestine tissues with a significant reduction in granuloma site. Treatment of S. mansoni-infected mice with Met or PZQ/Met ameliorated the hematological and biochemical alterations induced by S. mansoni infection. Collectively, Met has no anti-schistosomal activity but led to a reduction in egg deposition and showed an anti-fibrotic effect on granulomatous development either when used alone or in combination with PZQ treatment. This study shed light on the possible role of Met as an anti-fibrotic agent when administered with PZQ for S. mansoni infected humans.


Subject(s)
Anthelmintics , Diabetes Mellitus, Type 2 , Metformin , Praziquantel , Schistosomiasis mansoni , Adjuvants, Pharmaceutic/therapeutic use , Animals , Anthelmintics/administration & dosage , Anthelmintics/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Fibrosis , Granuloma/drug therapy , Male , Metformin/administration & dosage , Metformin/therapeutic use , Mice , Praziquantel/administration & dosage , Praziquantel/therapeutic use , Schistosoma mansoni , Schistosomiasis mansoni/drug therapy
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