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Antimicrobial Agents and Chemotherapy May 2017Schistosomiasis, a major neglected tropical disease, affects more than 250 million people worldwide. Treatment of schistosomiasis has relied on the anthelmintic drug... (Review)
Review
Schistosomiasis, a major neglected tropical disease, affects more than 250 million people worldwide. Treatment of schistosomiasis has relied on the anthelmintic drug praziquantel (PZQ) for more than a generation. PZQ is the drug of choice for the treatment of schistosomiasis; it is effective against all major forms of schistosomiasis, although it is less active against juvenile than mature parasites. A pyrazino-isoquinoline derivative, PZQ is not considered to be toxic and generally causes few or transient, mild side effects. Increasingly, mass drug administration targeting populations in sub-Saharan Africa where schistosomiasis is endemic has led to the appearance of reduced efficacy of PZQ, which portends the selection of drug-resistant forms of these pathogens. The synthesis of improved derivatives of PZQ is attracting attention, e.g., in the (i) synthesis of drug analogues, (ii) rational design of pharmacophores, and (iii) discovery of new compounds from large-scale screening programs. This article reviews reports from the 1970s to the present on the metabolism and mechanism of action of PZQ and its derivatives against schistosomes.
Topics: Africa South of the Sahara; Animals; Drug Resistance; Humans; Praziquantel; Schistosoma; Schistosomiasis; Schistosomicides
PubMed: 28264841
DOI: 10.1128/AAC.02582-16 -
PLoS Neglected Tropical Diseases Mar 2016In 2012 the World Health Assembly adopted resolution WHA65.21 on elimination of schistosomiasis, calling for increased investment in schistosomiasis control and support... (Review)
Review
Schistosomiasis Prevalence and Intensity of Infection in Latin America and the Caribbean Countries, 1942-2014: A Systematic Review in the Context of a Regional Elimination Goal.
BACKGROUND
In 2012 the World Health Assembly adopted resolution WHA65.21 on elimination of schistosomiasis, calling for increased investment in schistosomiasis control and support for countries to initiate elimination programs. This study aims to analyze prevalence and intensity of Schistosoma mansoni infection in children in Latin America and the Caribbean countries and territories (LAC), at the second administrative level or lower.
METHODOLOGY
A systematic review of schistosomiasis prevalence and intensity of infection was conducted by searching at PubMed, LILACS and EMBASE. Experts on the topic were informally consulted and institutional web pages were reviewed (PAHO/WHO, Ministries of Health). Only SCH infection among children was registered because it can be a 'proxi-indicator' of recent transmission by the time the study is conducted.
PRINCIPAL FINDINGS
One hundred thirty two full-text articles met the inclusion criteria and provided 1,242 prevalence and 199 intensity of infection data points. Most of them were from Brazil (69.7%). Only Brazil published studies after 2001, showing several 'hot spots' with high prevalence. Brazil, Venezuela, Suriname and Saint Lucia need to update the epidemiological status of schistosomiasis to re-design their national programs and target the elimination of Schistosoma mansoni transmission by 2020. In Antigua and Barbuda, Dominican Republic, Guadeloupe, Martinique, Montserrat and Puerto Rico schistosomiasis transmission may be interrupted. However the compilation of an elimination dossier and follow-up surveys, per WHO recommendations, are needed to verify that status. Hence, the burden of subtle SCH chronic infection may be still present and even high in countries that may have eliminated transmission. Heterogeneity in the methodologies used for monitoring and evaluating the progress of the schistosomiasis programs was found, making cross-national and chronological comparisons difficult.
CONCLUSIONS
There is a need for updating the schistosomiasis status in the historically endemic countries and territories in LAC to address the required public health interventions for control and elimination programs or to verify the elimination of transmission of Schistosoma mansoni. Improved reporting and standardization of the monitoring and evaluation methodologies used are recommended, while using available WHO guidelines. Meeting a regional elimination goal will require additional and improved epidemiological data by age group and sex.
Topics: Anthelmintics; Disease Eradication; Humans; Latin America; Praziquantel; Schistosomiasis
PubMed: 27007193
DOI: 10.1371/journal.pntd.0004493 -
World Journal of Gastroenterology Jul 2023Schistosomiasis (bilharziasis) is a major neglected tropical disease. It is endemic in many tropical and subtropical communities. Schistosomal polyps (S. polyps) are not... (Review)
Review
Schistosomiasis (bilharziasis) is a major neglected tropical disease. It is endemic in many tropical and subtropical communities. Schistosomal polyps (S. polyps) are not uncommon presentation of this infection. Although the colon is the most commonly affected organ, many other organs are affected. S. polyps are associated with a variable range of morbidity independent of the Schistosomal infection. S. polyps are frequently described in endemic areas and increasingly reported in non-endemic areas mainly among immigrants and visitors to the endemic areas. This review aimed to increase awareness of practitioners, especially gastroenterologists, for this peculiar type of polyps caused by this neglected infection hence improving patient outcomes. Web-based search of different databases was conducted for the literature focusing the development of S. polyps in the colon and other organs with analysis of the clinical manifestations, diagnosis and treatment. The following key words were used in the search, "Schistosomiasis" OR "Bilharziasis" AND "Polyps" OR "Polyp" AND "Colon" OR "Small intestine" OR " Duodenum" OR " Stomach" OR "Esophagus" OR " Gallbladder" OR" Pharynx" OR "Larynx" OR "Trachea" OR "Urinary bladder" OR " Ureter" OR "Renal Pelvis" OR "Urethra". All publication types including case reports, case series, original research, and review articles were retrieved and analyzed. S. polyps are not infrequent presentation of acute or chronic Schistosomal infection. S. polyps are described in many organs including the bowel, genitourinary tract, skin, gallbladder and the larynx. Presentation of S. polyps is variable and depends on the site, number as well as the polyp size. The relationship of to malignant transformation is a matter of discussion. Presence of S. polyps is sometimes the only manifestation of Schistosomiasis. Small polyps can be treated medically with praziquantel, while large accessible polyps are amendable for endoscopic excision through different polyp resection techniques. However, huge, complicated, non-accessible and suspicious polyps are indicated for surgical management or advanced endoscopic resection when appropriate. Clinicians and endoscopists should be aware about these facts when treating patients living in, immigrated from or visiting endemic areas.
Topics: Humans; Schistosomiasis; Praziquantel; Colon; Polyps
PubMed: 37475844
DOI: 10.3748/wjg.v29.i26.4156 -
BMC Public Health Jun 2023Schistosomiasis poses a serious public health problem and a social challenge affecting over 240 million people, the majority of whom live in sub-Saharan Africa. The... (Review)
Review
Health-seeking behaviour regarding schistosomiasis treatment in the absence of a mass drug administration (MDA) program: the case of endemic communities along Lake Albert in Western Uganda.
INTRODUCTION
Schistosomiasis poses a serious public health problem and a social challenge affecting over 240 million people, the majority of whom live in sub-Saharan Africa. The World Health Organization (WHO) recommends praziquantel (PZQ) drug treatment through regular mass drug administration (MDA) accompanied by social mobilisation and health education and sensitisation. With social mobilisation and health education and sensitisation, there is bound to be increased demand for the PZQ, especially in the case of endemic communities. However, it is not clear where communities go for PZQ treatment in the absence of PZQ MDA. We explored the health-seeking behaviours regarding schistosomiasis treatment among communities along Lake Albert in Western Uganda when MDA had delayed, to inform a review of the implementation policy for the achievement of the WHO's 2030 target of 75% coverage and uptake.
METHODS AND MATERIALS
We conducted a community-based qualitative study in Kagadi and Ntoroko, an endemic community in January and February 2020. We interviewed 12 individuals: local leaders, village health teams, and health workers, and conducted 28 focus group discussion sessions with 251 purposively selected community members. The audio recordings of the data were transcribed and analyzed using a thematic analysis model.
RESULTS
Generally, participants seldom seek medication for schistosomiasis-related signs and symptoms from government hospitals and health centres II, III and IV. Instead, they rely on community volunteers such as VHTs, private facilities, such as clinics and drug shops nearby, or traditional sources (e.g. witch doctors and herbalists). Results show that factors influencing people to seek treatment from sources other than the government are: the absence of PZQ drugs in the government health facility; health workers' negative attitude towards patients; long distances to the government hospitals and health facilities; poor and inaccessible roads; medication-related costs; and negative perceptions of the PZQ drug.
CONCLUSIONS
Availability and accessibility of PZQ seem to be a big challenge. PZQ uptake is further hampered by health systems and community-related and socio-cultural factors. Thus there is a need to bring schistosomiasis drug treatment and services closer to endemic communities, stock nearby facilities with PZQ and encourage endemic communities to take the drug. Contextualised awareness-raising campaigns are needed to debunk myths and misconceptions surrounding the drug.
Topics: Humans; Mass Drug Administration; Uganda; Lakes; Schistosomiasis; Praziquantel; Patient Acceptance of Health Care; Anthelmintics
PubMed: 37277773
DOI: 10.1186/s12889-023-16020-z -
Systematic Reviews Oct 2022The early childhood development of millions of children in some low- and medium-income countries may be compromised by schistosomiasis infections contracted at the age...
BACKGROUND
The early childhood development of millions of children in some low- and medium-income countries may be compromised by schistosomiasis infections contracted at the age of 5 years and below. Currently, there are no standard guidelines for treating schistosomiasis in children that are 5 years and younger using praziquantel (PZQ), the only drug that the World Health Organization (WHO) recommends for treating schistosomiasis. The review is on processes and resources involved in the treatment of schistosomiasis in children aged 5 years and below.
METHODS
An electronic search for peer-reviewed articles published in the period from January 2011 to August 2021 was done in the Academic Search Complete, CINAHL with Full Text, Health Source: Nursing/Academic Edition, and MEDLINE databases via EBSCOHost and Google Scholar databases. The search targeted journals that described the treatment of schistosomiasis in children 5 years and below using praziquantel.
RESULTS
Thirteen studies met the inclusion criteria. The patient journey for treating schistosomiasis in children aged 5 years old and below using PZQ included the following activities: enrolment of the children into the treatment program; clinical examination; diagnosis; taking anthropometric measurements; feeding the children, making the PZQ palatable to the children; administration of PZQ; and monitoring of side effects. There was also a variation in the resources used to treat children aged 5 and below for schistosomiasis.
CONCLUSIONS
A PZQ mass drug administration program for children aged 5 years old and below in endemic areas should exclude the diagnosis of schistosomiasis before treatment. The resources required in the treatment process should be affordable, and should not require skills and maintenance resources that are beyond those that are available at the primary healthcare level.
Topics: Child; Child, Preschool; Humans; Praziquantel; Mass Drug Administration; Anthelmintics; Schistosomiasis; Drug-Related Side Effects and Adverse Reactions
PubMed: 36271455
DOI: 10.1186/s13643-022-02087-z -
Parasites & Vectors Jun 2019Treatment of schistosomiasis has relied on the anthelmintic drug praziquantel (PZQ) for more than a generation. Despite its celebrated performance for treatment and...
BACKGROUND
Treatment of schistosomiasis has relied on the anthelmintic drug praziquantel (PZQ) for more than a generation. Despite its celebrated performance for treatment and control of schistosomiasis and other platyhelminth infections, praziquantel has some shortcomings and the inability of this drug to counteract disease sequelae prompts the need for novel therapeutic strategies.
METHODS
Using a host-parasite model involving Biomphalaria glabrata and Schistosoma mansoni we established mechanical transformation of S. mansoni cercariae into newly transformed schistosomula (NTS) and characterized optimal culture conditions. Thereafter, we investigated the antischistosomal activity and ability of the antioxidants N-acetylcysteine (NAC) and resveratrol (RESV) to augment the performance of praziquantel and/or artesunate (AS) against larval stages of the parasite. Drug effects were evaluated by using an automated microscopical system to study live and fixed parasites and by transmission electron microscopy (TEM).
RESULTS
Transformation rates of cercariae to schistosomula reached ~ 70% when the manipulation process was optimized. Several culture media were tested, with M199 supplemented with HEPES found to be suitable for S. mansoni NTS. Among the antioxidants studied, RESV alone or combined with anthelminthic drugs achieved better results rather N-acetylcysteine (NAC). TEM observations demonstrated that the combination of AS + RESV induced severe, extensive alterations to the tegument and subtegument of NTS when compared to the constituent compounds alone. Two anthelmintic-antioxidant combinations, praziquantel-resveratrol [combination index (CI) = 0.74] and artesunate-resveratrol (CI = 0.34) displayed moderate and strong synergy, respectively.
CONCLUSIONS
The use of viability markers including staining with propidium iodide increased the accuracy of drug screening assays against S. mansoni NTS. The synergies observed might be the consequence of increased action by RESV on targets of AS and PZQ and/or they may act through concomitantly on discrete targets to enhance overall antischistosomal action. Combinations of active agents, preferably with discrete modes of action including activity against developmental stages and/or the potential to ameliorate infection-associated pathology, might be pursued in order to identify novel therapeutic interventions.
Topics: Acetylcysteine; Animals; Antioxidants; Antiprotozoal Agents; Artesunate; Biomphalaria; Drug Synergism; Female; Larva; Male; Plant Extracts; Praziquantel; Resveratrol; Schistosoma mansoni; Schistosomiasis
PubMed: 31221193
DOI: 10.1186/s13071-019-3566-9 -
Scientific Reports Sep 2021Praziquantel pharmacokinetics studies in schistosomiasis infected children are scarce partly due to the challenges/complexity of intensive blood sampling in the target...
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 (AUC) and plasma concentrations at each specific sampling time-point was determined by Pearson's correlation coefficient (r). 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 AUC for both total praziquantel (r = 0.81, p < 0.001) and S-praziquantel (r = 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 AUC (r = 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.
Topics: Administration, Oral; Adolescent; Animals; Anthelmintics; Biological Availability; Blood Specimen Collection; Child; Chromatography, Liquid; Drug Monitoring; Feces; Female; Humans; Isomerism; Male; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni; Tandem Mass Spectrometry
PubMed: 34504222
DOI: 10.1038/s41598-021-97409-x -
The American Journal of Tropical... Jan 2021Spinal sparganosis of the cauda equina has been rarely reported. A 54-year-old man presented at the hospital after having experienced lower back pain for 10 months,... (Review)
Review
Spinal sparganosis of the cauda equina has been rarely reported. A 54-year-old man presented at the hospital after having experienced lower back pain for 10 months, progressive weakness and numbness of the left leg for 4 months, and urinary incontinence for 3 weeks. Magnetic resonance imaging of the lumbosacral spine revealed a heterogeneous enhancing mass at the T12-S1 level. Spinal sparganosis was diagnosed by histological examination and molecular identification of the parasite in the tissue section. The patient was treated with a high dose of praziquantel because the parasitic mass was only partially removed and symptoms worsened following surgery.
Topics: Anthelmintics; Anti-Ulcer Agents; Cauda Equina; Cimetidine; Humans; Male; Middle Aged; Polyradiculopathy; Praziquantel; Sparganosis
PubMed: 33124542
DOI: 10.4269/ajtmh.20-0712 -
BMC Infectious Diseases Dec 2022Urogenital schistosomiasis is a neglected tropical disease most prevalent in sub-Saharan Africa. In the Senegal river basin, the construction of the Diama dam led to an...
BACKGROUND
Urogenital schistosomiasis is a neglected tropical disease most prevalent in sub-Saharan Africa. In the Senegal river basin, the construction of the Diama dam led to an increase and endemicity of schistosomiasis. Since 2009, praziquantel has frequently been used as preventive chemotherapy in the form of mass administration to Senegalese school-aged children without monitoring of the treatment efficacy and the prevalence after re-infection. This study aims to determine the current prevalence of urogenital schistosomiasis (caused by Schistosoma haematobium), the efficacy of praziquantel, and the re-infection rates in children from five villages with different water access.
METHODS
The baseline prevalence of S. haematobium was determined in August 2020 in 777 children between 5 and 11 years old and a single dose of praziquantel (40 mg/kg) was administered to those positive. The efficacy of praziquantel and the re-infection rates were monitored 4 weeks and 7 months after treatment, respectively, in 226 children with a high intensity of infection at baseline.
RESULTS
At the baseline, prevalence was low among children from the village of Mbane who live close to the Lac de Guiers (38%), moderate among those from the villages of Dioundou and Khodit, which neighbor the Doue river (46%), and very high at Khodit (90.6%) and Guia (91.2%) which mainly use an irrigation canal. After treatment, the observed cure rates confirmed the efficacy of praziquantel. The lowest cure rate (88.5%) was obtained in the village using the irrigation canal, while high cure rates were obtained in those using the lake (96.5%) and the river (98%). However, high egg reduction rates (between 96.7 and 99.7%) were obtained in all the villages. The re-infection was significantly higher in the village using the canal (42.5%) than in the villages accessing the Lac de Guiers (18.3%) and the Doue river (14.8%).
CONCLUSION
Praziquantel has an impact on reducing the prevalence and intensity of urogenital schistosomiasis. However, in the Senegal river basin, S. haematobium remains a real health problem for children living in the villages near the irrigation canals, despite regular treatment, while prevalence is declining from those frequenting the river and the Lac de Guiers. Trial registration ClinicalTrials.gov, NCT04635553. Registered 19 November 2020 retrospectively registered, https://www.
CLINICALTRIALS
gov/ct2/show/NCT04635553?cntry=SN&draw=2&rank=4.
Topics: Child; Animals; Humans; Child, Preschool; Praziquantel; Schistosomiasis haematobia; Reinfection; Senegal; Prevalence; Rivers; Schistosoma haematobium; Water Supply; Anthelmintics
PubMed: 36581796
DOI: 10.1186/s12879-022-07813-5 -
The Cochrane Database of Systematic... Aug 2014Urinary schistosomiasis is caused by an intravascular infection with parasitic Schistosoma haematobium worms. The adult worms typically migrate to the venous plexus of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Urinary schistosomiasis is caused by an intravascular infection with parasitic Schistosoma haematobium worms. The adult worms typically migrate to the venous plexus of the human bladder and excrete eggs which the infected person passes in their urine. Chronic infection can cause substantial morbidity and long-term complications as the eggs become trapped in human tissues causing inflammation and fibrosis. We summarised evidence of drugs active against the infection. This is new edition of a review first published in 1997.
OBJECTIVES
To evaluate the efficacy and safety of drugs for treating urinary schistosomiasis.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, CENTRAL, EMBASE and LILACS and reference lists of articles up to 23 May 2014.
SELECTION CRITERIA
Randomized controlled trials (RCTs) of antischistosomal drugs and drug combinations compared to placebo, no intervention, or each other.
DATA COLLECTION AND ANALYSIS
Two researchers independently screened the records, extracted the data and assessed risk of bias. The primary efficacy outcomes were parasitological failure (defined as the continued presence of S. haematobium eggs in the urine at time points greater than one month after treatment), and percent reduction of egg counts from baseline. We presented dichotomous data as risk ratios (RR), and continuous data as mean difference (MD), alongside their 95% confidence intervals (CIs). Where appropriate we combined trials in meta analyses or tables. We assessed the quality of evidence using the GRADE approach.
MAIN RESULTS
We included 30 RCTs enrolling 8165 participants in this review. Twenty-four trials were conducted in children in sub-Saharan Africa, and 21 trials were over 20 years old. Many studies were assessed as being at unclear risk of bias due to inadequate descriptions of study methods. PraziquantelOn average, a single 40 mg/kg dose of praziquantel reduced the proportion of people still excreting eggs in their urine by around 60% compared to placebo at one to two months after treatment (treatment failure: RR 0.42, 95% CI 0.29 to 0.59, 864 participants, seven trials, high quality evidence). The proportion of people cured with praziquantel varied substantially between trials, from 22.5% to 83.3%, but was higher than 60% in five of the seven trials. At one to two months following praziquantel treatment at 40 mg/kg, the mean number of schistosome eggs in the urine was reduced by over 95% in five out of six trials (678 participants, six trials, high quality evidence).Splitting praziquantel 40 mg/kg into two doses over 12 hours probably has no benefits over a single dose, and in a single trial of 220 participants the split dose caused more vomiting (RR 0.5, 95% CI 0.29 to 0.86) and dizziness (RR 0.39, 95% CI 0.16 to 0.94). MetrifonateA single dose of metrifonate 10 mg/kg reduced egg excretion (210 participants, one trial, at eight months), but was only marginally better than placebo at achieving cure at one month (RR 0.83, 95% CI 0.74 to 0.94, 142 participants, one trial). In a single trial comparing one, two and three doses, the absolute number of participants cured improved from 47% after one dose to 81% after three doses (93 participants, one trial, low quality evidence).Two small trials compared 40 mg/kg single dose praziquantel with two or three doses of 10 mg/kg metrifonate and found no clear evidence of differences in cure (metrifonate 2 x 10 mg/kg at one month: RR 1.03, 95% CI 0.8 to 1.34, 72 participants, one trial; metrifonate 3 x 10 mg/kg at three months: RR 0.33, 95% CI 0.07 to 1.57, 100 participants, one trial. In one trial both drugs performed badly and in one trial both performed well. Other drugsThree trials have evaluated the antimalarial artesunate; with inconsistent results. Substantial antischistosomal effects were only seen in one of the three trials, which was at unclear risk of bias due to poor reporting of the trial methods. Similarly, another anti-malarial mefloquine has been evaluated in two small trials with inconsistent effects.Adverse events were described as mild for all evaluated drugs, but adverse event monitoring and reporting was generally of low quality.
AUTHORS' CONCLUSIONS
Praziquantel 40 mg/kg is the most studied drug for treating urinary schistosomiasis, and has the strongest evidence base.Potential strategies to improve future treatments for schistosomiasis include the combination of praziquantel with metrifonate, or with antimalarial drugs with antischistosomal properties such as artesunate and mefloquine. Evaluation of these combinations requires rigorous, adequately powered trials using standardized outcome measures.
Topics: Adult; Anthelmintics; Artemisinins; Artesunate; Child; Humans; Mefloquine; Praziquantel; Randomized Controlled Trials as Topic; Schistosomiasis haematobia; Trichlorfon
PubMed: 25099517
DOI: 10.1002/14651858.CD000053.pub3