Efficacy of praziquantel treatment regimens in pre-school and school aged children infected with schistosomiasis in sub-Saharan Africa: a systematic review.

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malaria 1 infectiousdiseases
praziquantel 70 infectiousdiseasesdrugs
schistosomiasis 12 infectiousdiseases
intestinal schistosomiasis 1 infectiousdiseases

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praziquantel 49 Title: Infectious Diseases of PovertyEfficacy of praziquantel treatment regimens in pre-school and school aged children infected with schistosomiasis in sub-Saharan
praziquantel 835 review was conducted to identify gaps and recent progress on the efficacy of different regimens of praziquantel in treating schistosomiasis among children in sub-Saharan Africa where Schistosoma mansoni and S. haematobium
praziquantel 1252 operators. The search included studies published from 2008 to 2017 (August) with emphasis on the efficacy of praziquantel on S. haematobium and S. mansoni infections among preschool and school children. Nineteen publications
praziquantel 2353 The review indicates that further investigations are necessary to conclusively determine efficacy of praziquantel on coinfection of S. haematobium and S. mansoni to formulate concrete guidelines on the use of repeated
praziquantel 2622 schistosomiasis. We recommend the use of the egg reduction rate (ERR) formula recommended by the WHO for assessing praziquantel efficacy in order for the results to be comparable for different regions.Electronic supplementary materialThe
praziquantel 3490 required preventive treatment and only 42.1 million were reported to have been treated [[2]]. To date, praziquantel administered at the standard single oral dose of 40 mg/kg body weight is the mainstay drug recommended
praziquantel 3846 countries to reduce the morbidity of the disease [[4]].In sub-Saharan Africa, studies have shown that praziquantel drastically reduces morbidity and transmission of schistosomiasis. It has a high cure rate (CR) and
praziquantel 4104 [6]]. However, failure/resistant cases have been reported after the use of a single standard dose of praziquantel at 40 mg/kg body weight. A repeated standard dose regimen has been shown to be more efficacious than
praziquantel 4481 mg/kg body weight to prevent failure/resistant cases. Researchers that conducted comparative studies of praziquantel with the standard dose of 40 mg/kg versus 60 mg/kg at a split dose [[8], [9]] reported divergent results.
praziquantel 5029 stage [[10]] and infection intensity have been attributed to influence the treatment outcomes with praziquantel with regard to the CR and ERR. Praziquantel is reported to be more efficacious on S. japonicum than
praziquantel 5287 lowest CR among mixed infections of S. haematobium and S. mansoni [[7], [11]]. It is also known that praziquantel is not effective on immature worms [[12]]. Moreover, schistosome resistance to praziquantel treatment
praziquantel 5379 known that praziquantel is not effective on immature worms [[12]]. Moreover, schistosome resistance to praziquantel treatment following its repeated dose use has been reported in field studies [[10]].Since there is no
praziquantel 5574 [[10]].Since there is no vaccine to prevent Schistosoma infection, regular monitoring of the efficacy of praziquantel is crucial. Studies on S. mansoni and S. japonicum focusing on the genetic diversity of the parasite
praziquantel 5707 on S. mansoni and S. japonicum focusing on the genetic diversity of the parasite as the determinant praziquantel efficacy have been conducted in Japan, China and the Philippines. Since praziquantel is not active on
praziquantel 5792 the determinant praziquantel efficacy have been conducted in Japan, China and the Philippines. Since praziquantel is not active on immature worms [[12]], a combination of praziquantel with antimalarial drugs (artemether,
praziquantel 5862 China and the Philippines. Since praziquantel is not active on immature worms [[12]], a combination of praziquantel with antimalarial drugs (artemether, artesunate) which kill immature worms has been suggested as a comprehensive
praziquantel 6203 S. mansoni and S. haematobium are endemic, particularly among children, studies on the efficacy of praziquantel are limited and the few studies that investigated the relationship between morbidity due to S. haematobium
praziquantel 6495 [16]]. This highlights the need for further investigations on the efficacy/failure of different doses of praziquantel against S. haematobium and S. mansoni in endemic areas of sub-Saharan African. In this paper we reviewed
praziquantel 6634 S. mansoni in endemic areas of sub-Saharan African. In this paper we reviewed the status of use of praziquantel and identified gaps in the treatment of schistosomiasis in the sub-Saharan region? Electronic searches
praziquantel 6800 schistosomiasis in the sub-Saharan region? Electronic searches focusing on the efficacy of different regimens of praziquantel in treating schistosomiasis among children in sub-Saharan Africa were done to extract literature on
praziquantel 7117 PubMed, MEDLINE and Google Scholar databases was carried out using following terms and Boolean operators: praziquantel AND efficacy AND resistance AND schistosomiasis AND Schistosoma haematobium OR Schistosoma mansoni AND
praziquantel 7850 criteriaPublications in peer-reviewed journals that focused on field studies on the efficacy and resistance/failure of praziquantel on S. haematobium and S. mansoni treatment among children in sub-Saharan Africa were included in the
praziquantel 8119 conducted among children less than 18 years old were also included in the review. Studies in which praziquantel was administrated at 40 mg single standard dose and/or repeated standard dose or at escalating dose
praziquantel 8426 excluded:Reports on work that involving both children and adults;Studies that reported on the efficacy of praziquantel combined with other anti-schistosomal drugs;Studies that assessed the efficacy of praziquantel in the
praziquantel 8521 efficacy of praziquantel combined with other anti-schistosomal drugs;Studies that assessed the efficacy of praziquantel in the co-infection settings of schistosomiasis with other parasitic diseases like soil transmitted
praziquantel 8689 other parasitic diseases like soil transmitted helminthic diseases;Laboratory experimental studies on praziquantel efficacy;Studies in which praziquantel efficacy was assessed after more than nine weeks post first administration.Quality
praziquantel 8728 transmitted helminthic diseases;Laboratory experimental studies on praziquantel efficacy;Studies in which praziquantel efficacy was assessed after more than nine weeks post first administration.Quality assessment of the
praziquantel 10077 abstracts that were deemed relevant, 13 were excluded as they did not focus specifically on the efficacy of praziquantel against S. haematobium and/or S. mansoni in sub-Saharan Africa in a field setting. This gave a total
praziquantel 10383 (cohort and randomised control). Excluded studies were those that reported either on the efficacy of praziquantel in combination with other medications or experimental laboratory studies or reviews. Studies in which
praziquantel 10686 three studies whose full texts were reviewed, three were removed as the time line of assessing for praziquantel efficacy did not meet the inclusion criteria (3–9 weeks). An additional study was removed as it was
praziquantel 11100 studies search. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-AnalysesEfficacy of praziquantel by age groupThe reviewed studies were conducted among children. School-going children were the most
praziquantel 11456 studies (nine) were conducted between 2012 and 2013.The cure rate had been largely used in assessing praziquantel efficacy in the past. The use of the egg reduction rate was recently recommended [[17]]. In most studies
praziquantel 11641 recommended [[17]]. In most studies that were carried out among school going children, the efficacy of praziquantel improved significantly after the repeated standard dose of 40 mg/kg body weight [[18]–[23]]. Higher
praziquantel 12203 efficacy among children [[26]–[28]]. Efficacy was lower in children that received multiple rounds of praziquantel treatment than in those that did not receive any treatment before [[29]]. In response to the pressing
praziquantel 12406 the pressing need of standardizing treatment in pre-school children, alternative paediatric forms of praziquantel have been on trial. Crushed praziquantel has been reported to have satisfactory efficacy for all species
praziquantel 12447 treatment in pre-school children, alternative paediatric forms of praziquantel have been on trial. Crushed praziquantel has been reported to have satisfactory efficacy for all species [[30]] while praziquantel syrup (Epiquantel®)
praziquantel 12537 trial. Crushed praziquantel has been reported to have satisfactory efficacy for all species [[30]] while praziquantel syrup (Epiquantel®) showed diminished efficacy [[31]] for reasons not known.Distribution of studies
praziquantel 13431 [30]]. The rest of the infections were due to S. haematobium (Additional file 3: Table S2).Efficacy of praziquantel on S. haematobium and S. mansoniS. haematobium and S. mansoni both exist separately or in co-infection
praziquantel 13837 cure rates and possible resistance recently reported. This review shows that for most of the studies praziquantel had high efficacy on both species [[19], [22], [27], [28], [29], [34]]. However, higher efficacy was
praziquantel 14136 co-infection settings as shown in Additional file 4: Table S3.Efficacy of different dose regimens of praziquantel Praziquantel administered at 40 mg/kg body weight is the standard dose recommended by WHO for chemotherapy
praziquantel 14358 treating schistosomiasis. Articles reviewed mainly reported on the efficacy of different dosages of praziquantel used against both S. haeamtobium and/or S. mansoni in sub-Saharan Africa. Most studies used single dose
praziquantel 14704 administered in three studies while one study used the escalating dose (20/40/60 mg/kg). The efficacy of praziquantel varied significantly depending on whether it was single or repeated dose. Overall, the repeated dose
praziquantel 15047 and improved after the administration of the second dose [[23], [27], [31]–[33]]. In some studies, praziquantel given at single dose revealed high cure rates and egg reduction rates [[19], [28], [34], [35]] while
praziquantel 15218 reduction rates [[19], [28], [34], [35]] while they were low in others [[31], [36]]. Escalating dose of praziquantel was more efficacious at high dose than at low dose [[9]].DiscussionThe study reviewed the efficacy of
praziquantel 15352 at high dose than at low dose [[9]].DiscussionThe study reviewed the efficacy of different doses of praziquantel against S. mansoni and S. haematobium infection in endemic settings in sub-Saharan Africa. Our discussion
praziquantel 15933 that may require a second or high dose to clear the infection was reported [[36]]. This may be because praziquantel kills mature schistosomes while immature worms are not affected but later become mature and release
praziquantel 16102 affected but later become mature and release eggs at a later stage. Infection may also persist after praziquantel treatment due to the reduced susceptibility of juvenile parasites to the drug [[37]]. Such persistent
praziquantel 16314 persistent infections may then contain a significant amount of juvenile schistosomes that are refractory to praziquantel at the standard dose leading to lower cure rate and egg reduction rate. In high endemic areas where
praziquantel 16541 children had been subjected to several rounds of mass drug administration (MDA), it was evident that praziquantel at the standard dose was less efficacious among those that received higher rounds of praziquantel (8
praziquantel 16639 that praziquantel at the standard dose was less efficacious among those that received higher rounds of praziquantel (8 to 9) compared to those that received lesser rounds of treatment (1 and 5) [[38]]. Thus, the use
praziquantel 16755 to 9) compared to those that received lesser rounds of treatment (1 and 5) [[38]]. Thus, the use of praziquantel in MDA campaigns has raised concerns on the possibility of development of drug resistance. It is however
praziquantel 16937 development of drug resistance. It is however important to realize that the parasite may acquire tolerance to praziquantel that needs to be distinguished from resistance. Repeated doses of praziquantel have been reported to
praziquantel 17016 acquire tolerance to praziquantel that needs to be distinguished from resistance. Repeated doses of praziquantel have been reported to improve the outcomes of infection, post treatment [[7]]. Follow-ups after large
praziquantel 17179 infection, post treatment [[7]]. Follow-ups after large scale intervention such as MDA are needed since praziquantel is the only recommended drug for schistosomiasis at 40 mg/kg body weight and in most cases does not
praziquantel 17366 and in most cases does not completely clear the parasite.Studies that used repeated standard dose of praziquantel [[20], [33]] showed satisfactory efficacy after the second dose. These findings corroborate with those
praziquantel 17699 treatment and that was done 3–4 weeks following the initial treatment. Moreover, the outcomes of praziquantel efficacy varied depending on whether it was a single infection or mixed infection. Studies that focused
praziquantel 18682 endemic areas after several rounds of MDAs.In a study that used an escalating dose, the outcomes of praziquantel efficacy gradually improved with increasing dosage [[9]]. The initial dose of 20 mg/kg body weight was
praziquantel 18975 low efficacy. Consistent with the above, results from a laboratory experiment showed that the use of praziquantel , especially at a lower dose than the recommended curative dose may lead to development of resistance
praziquantel 19159 to development of resistance to the drug in future generations [[40]]. Another study that compared praziquantel given at 40 mg/kg and 60 mg/kg single doses reported satisfactory efficacy with both regimens. However,
praziquantel 19436 more minor and transient side effects were observed at 60 mg/kg regimen [[8]].This review showed that praziquantel was efficacious on both S. haematobium and S. mansoni with the former being more sensitive to praziquantel.
praziquantel 19543 praziquantel was efficacious on both S. haematobium and S. mansoni with the former being more sensitive to praziquantel . In another comparative study, the efficacy of praziquantel was shown to be higher against S. japonicum
praziquantel 19603 with the former being more sensitive to praziquantel. In another comparative study, the efficacy of praziquantel was shown to be higher against S. japonicum than other species [[11]]. Factors responsible for this
praziquantel 19834 clear and need further investigation in co-infection settings.ConclusionsThis review revealed that praziquantel administrated at a repeated standard dose of 40 mg/kg was more efficacious than the standard single
praziquantel 19981 standard dose of 40 mg/kg was more efficacious than the standard single dose of 40 mg/kg. The outcomes of praziquantel efficacy depended on whether it was mixed infection of S. haematobium and S. mansoni or a single focus
praziquantel 20127 was mixed infection of S. haematobium and S. mansoni or a single focus of infection. The efficacy of praziquantel in mixed infection foci required at least two rounds of standard dose at three weeks interval. Praziquantel
praziquantel 20390 be slightly more efficacious than other regimens. S. haematobium was shown to be more sensitive to praziquantel than S. mansoni. Praziquantel showed moderate efficacy in areas that had received multiple MDA. The
praziquantel 20902 use in control programmes in endemic areas of sub-Saharan Africa to prevent possible resistance to praziquantel .Additional filesAdditional file 1:Multilingual abstracts in the six official working languages of the
praziquantel 21107 languages of the United Nations. (PDF 417 kb)Additional file 2:Table S1. Summary of findings on the use of praziquantel against Schistosoma mansoni between 2008–2017 in sub-Saharan Africa. (DOCX 25 kb)Additional file 3:Table
praziquantel 21265 2008–2017 in sub-Saharan Africa. (DOCX 25 kb)Additional file 3:Table S2. Summary of findings on the use of praziquantel against Schistosoma haematobium between 2008–2017 in sub-Saharan Africa. (DOCX 22 kb)Additional file
praziquantel 21437 sub-Saharan Africa. (DOCX 22 kb)Additional file 4:Table S3. Summary of review of findings on the use of praziquantel on co-infection with Schistosoma haematobium and S. mansoni between 2008–2017 in sub-Saharan Africa.
Select Disease Character Offset Disease Term Instance
intestinal schistosomiasis 546 Praziquantel is the only drug recommended by the World Health Organization to treat both urogenital and intestinal schistosomiasis . The reliance on a single drug to treat a disease with such a huge burden has raised concerns of possible
malaria 5884 Philippines. Since praziquantel is not active on immature worms [[12]], a combination of praziquantel with anti malaria l drugs (artemether, artesunate) which kill immature worms has been suggested as a comprehensive cure
schistosomiasis 134 PovertyEfficacy of praziquantel treatment regimens in pre-school and school aged children infected with schistosomiasis in sub-Saharan Africa: a systematic reviewMuhubiri KabuyayaMoses John ChimbariSamson MukaratirwaPublication
schistosomiasis 557 the only drug recommended by the World Health Organization to treat both urogenital and intestinal schistosomiasis . The reliance on a single drug to treat a disease with such a huge burden has raised concerns of possible
schistosomiasis 860 identify gaps and recent progress on the efficacy of different regimens of praziquantel in treating schistosomiasis among children in sub-Saharan Africa where Schistosoma mansoni and S. haematobium are endemic.Main textA
schistosomiasis 2507 mansoni to formulate concrete guidelines on the use of repeated doses at 40 or 60 mg/kg for treating schistosomiasis . We recommend the use of the egg reduction rate (ERR) formula recommended by the WHO for assessing praziquantel
schistosomiasis 3909 sub-Saharan Africa, studies have shown that praziquantel drastically reduces morbidity and transmission of schistosomiasis . It has a high cure rate (CR) and satisfactory egg reduction rate (ERR) [[5], [6]]. However, failure/resistant
schistosomiasis 6687 In this paper we reviewed the status of use of praziquantel and identified gaps in the treatment of schistosomiasis in the sub-Saharan region? Electronic searches focusing on the efficacy of different regimens of praziquantel
schistosomiasis 6825 region? Electronic searches focusing on the efficacy of different regimens of praziquantel in treating schistosomiasis among children in sub-Saharan Africa were done to extract literature on the subject.Main textReview
schistosomiasis 7162 carried out using following terms and Boolean operators: praziquantel AND efficacy AND resistance AND schistosomiasis AND Schistosoma haematobium OR Schistosoma mansoni AND sub-Saharan Africa. At the initial stage of identifying
schistosomiasis 8566 anti-schistosomal drugs;Studies that assessed the efficacy of praziquantel in the co-infection settings of schistosomiasis with other parasitic diseases like soil transmitted helminthic diseases;Laboratory experimental studies
schistosomiasis 13688 efficacious on all species, therefore, it is the only recommended drug for preventing and treating schistosomiasis [[2]] despite some observed low cure rates and possible resistance recently reported. This review shows
schistosomiasis 14267 administered at 40 mg/kg body weight is the standard dose recommended by WHO for chemotherapy in treating schistosomiasis . Articles reviewed mainly reported on the efficacy of different dosages of praziquantel used against
schistosomiasis 17225 large scale intervention such as MDA are needed since praziquantel is the only recommended drug for schistosomiasis at 40 mg/kg body weight and in most cases does not completely clear the parasite.Studies that used repeated

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