Efficacy and side effects of praziquantel in the treatment of Schistosomiasis mansoni in schoolchildren in Shesha Kekele Elementary School,Wondo Genet,Southern Ethiopia

Objective:To evaluate the efficacy and side effects of praziquantel(PZQ) in the treatment of schistosomiasis in Ethiopia.Methods:In a cross-sectional study,stool specimens were collected from randomly selected 299 school children in Shesha Kekele Elementary School,Wondo Genet, Southern Ethiopia,in April 2010.Stool specimens were examined using a single Kato-Katz thick smear for Schistosoma mansoni(5.mansoni) ova.Children who were found positive for S.mansoni were treated with a single oral dose of PZQ at 40 mg/kg bw and interviewed for treatment-related symptoms 24 hours after drug administration.Four weeks post-treatment,stool specimens were collected from the same children and examined following the same procedure as in the pretreatment.Drug efficacy was determined based on cure and egg reduction rates.Results:Pretreatment prevalence of S.mansoni infection was 74.9%with geometric mean egg count of 268. The evaluated generic PZQ produced an overall cure rate of 73.6%(P<0.000 1,OR:8.33,CI:5.3-13.1) and egg reduction rate of 68.2%(P=0.03,F=0.64).The cure rate showed significant association with age(x^2=H,P=0.004),the highest rate being observed in the 15-22 age group.83%of S. mansoni infected children showed various treatment-related symptoms,the most frerjiient being headache,nausea,and abdominal pain.These symptoms were associated with age(P<0.001) and pre-treatment intensity of infection(P<0.05).Conclusions:The present observations revealed relatively lower cure and egg reduction rates of the PZQ evaluated as compared to previous reports for other PZQ brands in Ethiopia.Hence,in depth studies are recommended to clarify whether the present relatively lower cure rate is the actual cure rate of the praziquantel evaluated,treatment failure,or reduced susceptibility of the parasite.Treatment-related side effects observed were transient and tolerable.

Metabolism of Praziquantel in Erythromycin, Acetylspi-ramycin and Dexamethasone Induced Rat Liver Micro-somes

Our results show that in liver microsomes from erythromycin,acetylspiramycin and dexamethsone pretreated rats,the rate of praziquantel( PQT)disappearence was increased as compared with control rat When microsomes from erythromycin-treated rats were exposed to PQT in the presence of potassium ferricyanide which broke down the cytochrome P-450 Fe(Ⅱ)-metabolite complexes and restored the functional cytochrome P-450,PQT metabolism was further increased. Acetylspiramycin did not form the complexes, so potassium ferricyanide showed no effect on the PQT metabolism in microsomes from acetylspiramycin-treated rats. Triacetyloleandomycin,a specific inhibitor of cytochrome P-450ⅢAI, inhibited PQT metabolism by 53% in liver microsomes from dexamethasone-treated rats.These results indicate the cytochrome P-450ⅢA seems to be involved in metabolism of PQT in rat liver microsomes.

In vitro/vivo assessment of praziquantel nanocrystals: Formulation, characterization, and pharmacokinetics in beagle dogs

To investigate the impact of particle size on in vitro/vivo performance of praziquantel(PZQ), nanocrystals(NCs) and microcrystals(MCs) of PZQ were prepared using the methods of wet milling and jet milling, respectively. PZQ NCs and MCs were characterized with dynamic light scattering, laser particle size analyzer, transmission electron microscopy, differential scanning calorimetry, X-ray powder diffraction and fourier transform infrared spectroscopy. The average diameters of PZQ NCs and MCs were 364.4 nm and 3.7 μm, respectively. No change in crystalline form was observed. Dissolution tests were performed in two different media, where the cumulative dissolution and dissolution rate of NCs were significantly improved in comparison with those of MCs and KANGQING~? in non-sink condition. Similarly, oral bioavailability of PZQ NCs in beagle dogs was 1.68( P < 0.05) and 1.83 fold( P < 0.01) higher than that of MCs and KANGQING~? . Considering the advantages of in vitro/vivo performance and facile preparation, PZQ NCs may have a great application in the treatment of schistosomiasis.

Reduction of Praziquantel Elimination by Cimetidine in Rats

The effect of cimetidine on the elimination of praziquantel(PQT)in rats was studied. The results showed that cimetidine 100 mg/kg,ip 2 reduced the clearances of intravenous and oral PQT by 60 and 69 percent respectively.Cimetidine also markedly reduced liver blood flow of rats(a reduction of 58%)and inhibited PQT metabolism in hepatic microsomes of rats(an inhibition of 55%). The reduction in clearance of intravenous PQT could be attributed to the result of cimetidine lowering liver blood flow,whereas the reduction in clearance of oral PQT might be related mainly to the inhibition of cimetidine on the activity of hepatic drug-metabolizing enzymes.

Effects of albendazole,artesunate,praziquantel and miltefosine,on Opisthorchis viverrini cercariae and mature metacercariae

Objective:To explore larvicidal effects of anthelmintic drugs on Opisthorchis viverrini(O.viverrini) for alternative approach to interrupting its cycle for developing a field-based control program.Methods:The larvicidal activities of albendazole(A1),artesunate(Ar),praziquantel(Pzq) and miltefosine(Mf) on O.viverrini cercariae and mature metacercariae were investigated.Lethal concentrations(LC_(50) and LC_(95)) of these drugs were determined.Mature metacercariae previously exposed to various concentrations of the drugs were administered to hamsters.Worms were harvested 30 d post infection and worm recovery rates calculated.Al,Ar,Pzq and Mf produced morphological degeneration and induced shedding tails of cercariae after 24 h exposure.Results:The LC_(50) and LC_(95) of Al,Ar,Pzq and Mf on cercariae were 0.720 and 1.139,0.350 and 0.861,0.017 and 0.693,and 0.530 and 1.134 ppm,respectively.LC_(50) and LC_(95) of Ar on mature metacercariae were 303.643 and 446.237 ppm and of Mf were 289.711 and 631.781 ppm,respectively but no lethal effect in Pzq-and Al-treated groups(up to 1 ppt).No worms were found in hamsters administered Pzq-treated metacercariae.The adult worms from Al-treated metacercariae were significantly bigger in size compared to the control group(P<0.05).Fecundity and body width were greater in adults from Mf-treated metacercariae compared to the control group(P<0.05).Conclusions:The larvicidal effects of these drugs were high efficacy to O.viverrini cercariae but lesser efficacy to metacercariae.It should be further studied with the eventual aim of developing a field-based control program.

Detection of Praziquantel Content in Praziquantel Injection by HPLC

[ Objective] To detect the praziquantel content in praziquantel injection by HPLC. [ Methods ] Chromatographic conditions were as follows： chromato- graphic colmnn was Diamonsil Cls column （ 150 mm x 4.6 mm, 5 μm） ; column temperature was 25 ℃ ; mobile phase was acetonitrile-water （60：40） ; flow rate was 1.0 mL/min ; UV detection wavelength was 210 nm; and injection volume was 20 μL. [ Results ] Praziquantel showed good linear relationship within the con- centration of 6.037 - 90.55 g/L （ r = 0. 999 4） ; the average recovery rate was 99.24%, and RSD was 0. 769%. [Condusions ] This method was simple, rap- id, sensitive and repeatable, and could be used for the quality control of praziquantel injection.

A useful quantitative model for determination of enantiomeric composition of racemate praziquantel by ultraviolet spectroscopy combined with partial least squares and its application to praziquantel tablets

A simple and novel method has been proposed to determine the enantiomeric composition ofracemate praziquantel(PzQ)by using the analysis of ultraviolet(UV)spectroscopy combinedwith partial least squares(PLS),This method does not rely on the use of expensive carbohydratessuch as cyclodextrins,but on the use of inexpensive sucrose,which is equally effective as car-bohydrate.PZQ has two enantiomers.Through measuring the slight diference in the UV spectralabsorption of PzQ due to different interactions between its two enantiomers and sucrose,theenantiomeric composition was determined by a quantitative model based on PLS analysis.Themodel showed that the correlation coeficients of calibration set and validation set were 0.9971and 0.9972,respectively.The root mean square error of calibration(RMSEC)and the root meansquare error of prediction(RMSEP)were 0.0167 and 0.0129,respectively,Then,the independentdata of PZQ tablets were also used to test how well the quantitative model of PLS predicted theenantiomeric composition,The ratio of S-PZQ in tablet was 0.492,determined by high-perfor-mance liquid chromatography as the reference value,Six solutions of the tablet samples were prepared,and the ratios of S-PZQ in tablet samples in the validation set were predicted by the PLS model.,Theirrelative erors with the reference value were not more than 4%.Therefore,the established model couldbe accurate and employed to predict the enantiomeric compositions of PzQ tablets.

The Use of Intramuscular Praziquantel in South-African Ruminants against Cestode Parasites. A First Pilot Study

The objective of this small pilot study was to test the efficacy and potential development for the use of Praziquantel IM Cestodicide in South African goats. Two farms were identified as infected with the Cestode Moniezia spp, and a test herd as well as a control herd was set aside on each of these farms. Fecal float coprological analyses were performed before and after treatment of the test herds, while no treatment was administered to the animals in the control herds of each farm. Praziquantel treatment proofed to be effective in reducing Cestode numbers based on egg counts using the Mac-Master method.

Praziquantel and Albendazole Pills Can Cure Cancer

Objective:To prevent and treat various types of cancer safely,reliably,and at low cost.Method:Early and mid-stage cancer patients took praziquantel and albendazole every day,late cancer patients only took albendazole every day,while with the traditional Chinese medicine“ginseng jade bamboo particle”to eliminate the adverse reactions and side effects caused by the above two western medicines,continue for more than three months.Conclusion:Praziquantel and albendazole have good therapeutic and cancer prevention effects in actual clinical trials.

Controlling schistosomiasis with praziquantel:How much longer without a viable alternative?

The current approach of morbidity control of schistosomiasis,a helminth disease of poverty with considerable public health and socioeconomic impact,is based on preventive chemotherapy with praziquantel.There is a pressing need for new drugs against this disease whose control entirely depends on this single drug that has been widely used over the past 40 years.We argue that a broader anthelminthic approach supplementing praziquantel with new antischistosomals targeting different parasite development stages would not only increase efficacy but also reduce the risk for drug resistance.Repositioning drugs already approved for other diseases provides a shortcut to clinical trials,as it is expected that such drugs rapidly pass the regulatory authorities.The antischistosomal properties of antimalarial drugs(e.g.,semisynthetic artemisinins,synthetic trioxolanes,trioxaquines and mefloquine)and of drugs being developed or registered for other purposes(e.g.,moxidectin and miltefosin),administered alone or in combination with praziquantel,have been tested in the laboratory and clinical trials.Another avenue to follow is the continued search for new antischistosomal properties in plants.Here,we summarise recent progress made in schistosomiasis chemotherapy,placing particular emphasis on repositioning of existing drugs against schistosomiasis.

Efficacy of praziquantel in the treatment of Schistosoma haematobium infection among school-age children in rural communities of Abeokuta, Nigeria

Background:Chemotherapy with praziquantel(PZQ)has been the cornerstone of schistosomiasis control over the last two decades.Being the only available drug for the treatment of over 200 million people worldwide,continuous monitoring of PZQ efficacy under the pressure of widespread use is therefore advocated.Methods:The efficacy of taking two doses of oral PZQ for the treatment of Schistosoma haematobium was examined among school children in Nigeria.Urine specimens were collected from 350 school children and examined using the filtration technique.Blood was collected for packed cell volume(PCV)estimation,and the weight and height of each child were estimated.S.haematobium egg positive pupils were treated with two oral doses of PZQ at 40 mg/kg with a four-week interval in between.Drug efficacy was determined based on the egg reduction rate(ERR).Results:Among 350 school children,245(70.0%)-of which 132 were males and 113 were females,with an age range of 4 to 15 years-were diagnosed with S.haematobium.All the 245 infected children received a single oral dose of 40 mg/kg PZQ twice with a four-week interval in between and were followed up for 12 weeks.At four,eight and twelve weeks post treatment,the ERR was 57.1%,77.6%and 100%,respectively.The ERR was significantly higher among the children with a light infection compared to those with a heavy infection.One hundred and twenty-one children were egg negative at four weeks post treatment,among which 1(6.3)and 120(52.4%)had heavy and light infections,respectively.Following the second round of treatment,the cure rate at eight weeks and twelve weeks was 85.3%and 100%,respectively.Conclusion:This study demonstrated the efficacy of taking two doses of oral PZQ for the treatment of urinary schistosomiasis among school children in Nigeria.

Efficacy of praziquantel on Schistosoma haematobium and re-infection rates among school-going children in the Ndumo area of uMkhanyakude district,KwaZulu-Natal,South Africa

Background:Despite its low cure rates and possible resistance,praziquantel(PZQ)is the only drug available for schistosomiasis treatment.Hence,monitoring its efficacy is crucial.This study assessed the efficacy of PZQ,determined re-infection and incidence rates of Schistosoma haematobium infection among school-going children in the Ndumo area,KwaZulu-Natal.Methods:A cohort of 320 school-going children(10-15 years)in 10 primary schools was screened for S.haematobium infection using the filtration technique.Infected children were treated at different times and hence were divided into two sub-cohorts;A1 and A2.Non-infected children constituted the sub-cohort B.Children who continued excreting viable eggs 4 weeks post-treatment received a second dose of PZQ.Re-infection rates were determined in sub-cohort A1 and A2 at 28 and 20 weeks post-treatment,respectively.Cure rates(CR)and egg reduction rates(ERR)were calculated.Incidence rate was assessed 28 weeks post baseline survey using children that were negative for schistosome eggs at that survey.Analysis of data was done using the Chi square and the Wilcoxon rank test.A 95%confidence interval with a P-value<0.05 determined significance.Results:At baseline,120(37.5%)of the 320 study participants were found infected with Schistosoma haematobium.Heavy infections accounted for 36.7%.The calculated cure rates were 88.07%and 82.92%for females and males,respectively.Egg Reduction Rates of 80%and 64%for females and males were observed 4 weeks after the initial treatment.After the second treatment,CR was 100%in females and 50%in males with an ERR of 100%in females and 70%in males.At 20 and 28 weeks post treatment,reinfection rates of 8.03%and 8.00%were observed,respectively,giving an overall rate of 8.1%.An incidence rate of 4.1%was observed 28 weeks after the baseline screening.Conclusions:The study indicated high CR while the ERR was low suggesting a reduced PZQ efficacy.The efficacy improved among females after the second dose.Re-infection rates at 20 and 28 weeks posttreatment were low.The study also indicated a low incidence rate for the 28 weeks period.

Factors associated with coverage of praziquantel for schistosomiasis control in the communitydirect intervention (CDI) approach in Mali (West Africa)

Background:Despite the progress made in the control of Neglected Tropical Diseases(NTD),schistosome and soil-transmitted helminth infections are far from being effectively managed in many parts of the world.Chemotherapy,the key element of all control strategies,is faced with some difficulties in terms of access to treatment.Our study aims to describe the factors involved in the success or failure of the community-directed intervention(CDI)approach through control programmes,which aims to achieve consistent high coverage at affordable and sustainable costs in endemic areas.Methods:The CDI approach was carried out from December 2007 to October 2008 in ten villages of the district of Diéma,Mali.At inclusion,each child part of the study’s sample was interviewed and submitted for a physical examination.The study focused on:data collection,treatment of the eligible population,evaluation of the treatment coverage,performance of community drug distributors(CDDs),and the involvement and perception of populations.Results:A total of 8,022 eligible people were studied with a mean coverage rate of 76.7%.Using multiple regression,it was determined that receiving praziquantel as treatment was associated with five factors:belonging to the Fulani or Moorish ethnic minority versus the Bambara/Soninke,use of the central versus the house-to-house drug distribution mode,the ratio of the population to the number of CDDs,the lack of supervision and belonging to the age group of 15 years or above(p<0.05).As well as that,it was found that the presence of parallel community-based programmes(HIV,tuberculosis)that provide financial incentives for community members discouraged many CDDs(who in most cases are volunteers)to participate in the CDI approach due to a lack of incentives.Conclusions:The findings indicate that the success of the CDI approach depends on,amongst other things,the personal characteristics of the respondents,as well as on community factors.

Slow-release praziquantel for dogs:presentation of a new formulation for echinococcosis control

Background:Echinococcosis is a serious,zoonotic,parasitic disease with worldwide distribution.According to a epidemiological survey in 2012 in China,there are 20,000 infected patients and more than 50 million people at the risk.As the dog is the main,definitive host,the Government of China encourages monthly praziquantel treatment of every dog.However,this is difficult to achieve in geographically challenging areas,such as the Tibetan plateau,where there are also many dogs without owners.To overcome these problems,we investigated the transmission blocking capacity of a slow-release formulation of praziquantel administered by subcutaneous injection.Methods:The impact of a slow-release preparation of two pharmacokinetically stereoselective praziquantel enantiomers,i.e.,R-(−)-praziquantel(R-PZQ)and S-(+)-praziquantel(S-PZQ)absorbed into a biodegradable polymer was studied in beagle dogs(N=6).The preparation was given by subcutaneous injection using a single dose of 100 mg/kg.Chiral-selective,high-performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)were applied to measure the praziquantel enantiomers in the plasma of the dogs.The lower limit for estimating plasma concentrations accurately for R-PZQ was 4 ng/ml and for S-PZQ 20 ng/ml.The pharmacokinetic parameters were calculated by a noncompartmental analysis model using Drug Analyze System(DAS)software 2.0.The SPSS 19.0 software was used for statistical analysis,and the statistical comparison between enantiomers was assessed using the two-tailed t-test.Results:Two hours after administration,peak concentrations of R-PZQ and S-PZQ:321±26 and 719±263 ng/ml,respectively,were achieved.After 180 days,the average plasma concentration of R-PZQ in the six dogs had decreased to 13 ng/ml.The average concentration value of S-PZQ was higher than that of R-PZQ in the first 90-day period but fell afterwards and could not be accurately estimated when dropping below 20 ng/ml(the lower methodological limit for this enantiomer).Taking all the dogs into account,the average maximum concentration(Cmax)of S-PZQ in plasma over the first 3 months was higher than that of R-PZQ by 114.0%(P<0.05),while the average mean retention time(MRT)of R-PZQ in plasma was higher than that of S-PZQ by 96.3%(P<0.05).Conclusions:Praziquantel given as an in situ slow-release formulation by subcutaneous injection resulted in concentrations of the active principle in beagle dogs,which should be capable of resisting new Echinococcus infections for at least 6 months.The new formulation of praziquantel represents a potential,alternative way of presenting medication against tapeworm infections in dogs.

Schistosomiasis control in Senegal:results from community data analysis for optimizing preventive chemotherapy intervention with praziquantel

Background Over the past two decades,preventive chemotherapy(PC)with praziquantel(PZQ)is the major strategy for controlling schistosomiasis in Senegal.The objective of this analysis was to update the endemicity of schistosomiasis at community level for better targeting mass treatment with PZQ in Senegal.Methods Demographic and epidemiological data from 1610 community health areas were analyzed using the schistosomiasis community data analysis tool of Expanded Special Project for Elimination of Neglected Tropical Diseases which developed by World Health Organization/Africa Ofce(WHO/AFRO).The tool uses a WHO/AFRO decision tree for areas without epidemiological data to determine whether mass treatment should be continued at community level.Descriptive analysis was performed.Results Overall,the endemicity of 1610 community health areas were updated based on the data from the district endemicity(33.5%)and the form of Join request for selected PC medicine(40.5%).Up to 282(17.5%)and 398(24.7%)of community health areas were classifed as moderate and high endemicity.41.1%of communities were non endemic.High endemicity was more important in Tambacounda,Saint Louis,Matam,Louga and Kedougou.A change in endemicity category was observed when data was disagregted from district level to community level.Implementation units classifed non endemic were more important at community level(n=666)compared to district level(n=324).Among 540 areas previously classifed high endemic at district level,392(72.6%)remained high prevalence category,while 92(17.0%)became moderate,43(8.0%)low and 13(2.4%)non-endemics at community level.Number of implementation units requiring PC was more important at district level(1286)compared to community level(944).Number of school aged children requiring treatment was also more important at district level compared to community level.Conclusions The analysis to disaggregate data from district level to community level using the WHO/AFRO schistosomiasis sub-district data optimization tool provide an update of schistosomiasis endemicity at community level.This study has allowed to better target schistosomiasis interventions,optimize use of available PZQ and exposed data gaps.

Praziquantel decreases fecundity in Schistosoma mansoni adult worms that survive treatment:evidence from a laboratory life-history trade-offs selection study

Background:Mass drug administration of praziquantel is the World Health Organization’s endorsed control strategy for schistosomiasis.A decade of annual treatments across sub-Saharan Africa has resulted in significant reductions of infection prevalence and intensity levels,although‘hotspots’remain.Repeated drug treatments place strong selective pressures on parasites,which may affect life-history traits that impact transmission dynamics.Understanding drug treatment responses and the evolution of such traits can help inform on how to minimise the risk of drug resistance developing,maximise sustainable control programme success,and improve diagnostic protocols.Methods:We performed a four-generation Schistosoma mansoni praziquantel selection experiment in mice and snails.We used three S.mansoni lines:a praziquantel-resistant isolate(R),a praziquantel-susceptible isolate(S),and a coinfected line(RS),under three treatment regimens:untreated,25 mg/kg praziquantel,or 50 mg/kg praziquantel.Lifehistory traits,including parasite adult-worm establishment,survival,reproduction(fecundity),and associated morbidity,were recorded in mice across all four generations.Predictor variables were tested in a series of generalized linear mixed effects models to determine which factors had a significant influence on parasite life-history traits in definitive hosts under different selection regimes.Results:Praziquantel pressure significantly reduced adult-worm burdens across all generations and isolates,including within R-lines.However,previous drug treatment resulted in an increase in adult-worm establishment with increasing generation from P1 to F3.The highest worm numbers were in the co-infected RS line.Praziquantel treatment decreased adult-worm burden,but had a larger negative impact on the mean daily number of miracidia,a proxy for fecundity,across all three parasite isolates.Conclusions:Our predicted cost of resistance was not supported by the traits we measured within the murine host.We did not find evidence for negative adult worm density-dependent effects on fecundity.In contrast,of the adult worms that survived treatment,even low doses of praziquantel significantly reduced adult-worm fecundity.Such reductions in worm fecundity post treatment suggest that egg-based measures of drug efficacy,such as Kato-Katz,may overestimate the short-term effect of praziquantel on adult-worm burdens.These findings have important implications for S.mansoni transmission control,diagnostic protocols,and the potential for undetected selection toward drug resistance.

Pharmacological and immunological effects of praziquantel against Schistosoma japonicum:a scoping review of experimental studies

Background:Chemotherapy for schistosomiasis has been around for 100 years.During the past century,great efforts have been made to develop new antischistosomal drugs from antimonials to nonantimonials,and some of these have been used extensively in clinical treatment.With the exception of a few drugs,such as oxamniquine and metrifonate,most of the antischistosomals developed in the pre-praziquantel period have variable limitations with respect to safety and efficacy.Although oxamniquine and metrifonate have been used for schistosomiasis control,they are only effective against Schistosoma mansoni and S.haematobium,respectively.Currently,praziquantel is the only drug used for treatment of all five species of human schistosomes.In this review,the pharmacological and immunological effects of praziquantel against S.japonicum are summarized and discussed.Main text:From the end of the 1970s until the 2000s,scientists have conducted a series of experimental studies on the effects of praziquantel against S.japonicum.These have included examining its unique pharmacological action on schistosomes,the characteristics in susceptibility of the different developmental stages of schistosomes to the drug,the relationship between plasma concentration of the drug and efficacy,the impact of host factors on cidal action of the drug,prevention and early treatment of schistosomal infection,as well as praziquantel-resistant schistosomiasis.Conclusion:The effects of praziquantel against S.japonicum,as elucidated by the experimental studies that are reviewed in this paper,may have some reference significance for the development of new antischistosomals.

Praziquantel efficacy against Schistosoma mansoni among HIV-1 infected and uninfected adults living in fishing villages along Lake Victoria, Northwest Tanzania

Background:Animal studies have demonstrated that functional immune responses,as determined by the levels of CD4+cell counts and anti-schistosome antibodies responses,determine the efficacy of praziquantel.Based on this evidence,it has been hypothesised that the immunodeficiency effects of the human immunodeficiency virus(HIV)-1 infection may affect the efficacy of praziquantel in co-infected human hosts.Thus,the present study assessed the efficacy of praziquantel by comparing parasitological cure rates and the reduction in infection intensity in HIV-1 seronegative individuals infected with S.mansoni and HIV-1 seropositive individuals co-infected with S.mansoni,following treatment with a single oral dose of praziquantel.Methods:This was a prospective longitudinal study which included,at baseline,555 S.mansoni infected adults aged 21-55 years,who were either co-infected or not with HIV-1 and who lived in fishing villages along Lake Victoria in Northwest Tanzania.These individuals were treated with a single oral dose of praziquantel(40 mg/kg)and,at 12 weeks,single stool samples were obtained and examined for S.mansoni eggs using the Kato-Katz technique.Finger prick and venous blood samples were collected for HIV-1 screening and CD4+cell quantification.Results:The parasitological cure rate did not differ significantly from the HIV-1 serostatus(P=0.12):among the co-infected individuals,the cure rate was 48.3%(14/29),and among the individuals infected only with S.mansoni,the cure rate was 62.6%(329/526).The egg reduction rate did not vary with the HIV-1 serostatus(P=0.22):77.22%for HIV-1 seronegative and 75%for HIV-1 seropositive individuals.The level of CD4^(+) cell counts(median 228 cells/μL:range 202-380 cells)did not influence the cure rate(P=0.23)or the reduction in the intensity of the infection(P=0.37).Conclusion:The HIV-1 infection per se or its moderate immunodeficiency effects,demonstrated by the range of CD4^(+) cell counts observed in co-infected individuals,did not affect praziquantel efficacy,as measured by the parasitological cure rate and the reduction in intensity of infection in the present study cohort.

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

Background:Schistosomiasis is a serious public health burden in sub-Saharan Africa.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 drug resistance mainly in endemic areas.This systematic 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 are endemic.Main text:A literature search of peer-reviewed journals was done on Google Scholar,MEDLINE(under EBSCOhost)and PubMed databases using pre-defined search terms and Boolean 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 satisfied the inclusion criteria for the review.The studies reviewed were from 10 sub-Saharan African countries and 7/19 of the studies(37%)were conducted in Uganda.Seven studies(37%)focused on Schistosoma mansoni,6/19(31.5%)on S.haematobium and another 6 on mixed infection.A single standard dose of 40 mg/kg body weight was the most used regimen(9)followed by the repeated single standard dose assessed for efficacy at 3-4 weeks post-treatment.Conclusions:A repeated standard dose of 40 mg/kg achieved satisfactory efficacy compared to a single dose against both parasite species.However,findings on efficacy of repeated doses in co-infection of S.mansoni and S.haematobium were not conclusive.Praziquantel administrated at 60 mg/kg was slightly more efficacious than the 40 mg/kg standard dose.Minor and transitory side-effects were reported for both regimens.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 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 efficacy in order for the results to be comparable for different regions.

Developing a comprehensive response for treatment of children under 6 years of age with schistosomiasis:research and development of a pediatric formulation of praziquantel

Schistosomiasis is a parasitic disease caused by blood flukes.The disease is caused by an inflammatory reaction to parasite eggs retained in the liver,bladder and reproductive organs.According to 2017 World Health Organization(WHO)estimates 220 million people are potentially infected,from which probably 10%are children under 6 years of age.The regular treatment approach of a single,oral dose of 40 mg/kg body weight with praziquantel however,is difficult for children under the age of 6,leaving them without a treatment option.In order to address this important gap in treatment target populations,an international public-private partnership that works on a not-for-profit basis in the field of drug research and development for schistosomiasis was established in 2012.This is called the Pediatric Praziquantel Consortium.Its mission was and continues to be to develop,register and provide access to a suitable pediatric praziquantel formulation for treating schistosomiasis in preschool-age children(3-6 months up to 6 years).The Target Product Profile for the pediatric formulation of praziquantel that would be suitable to treat children as young as 3-6 months was then defined by a group of experts,including members from the Pediatric Praziquantel Consortium partner organizations as well as experts from WHO(as observer)and schistosomiasis endemic countries.The development of the drug is ongoing and the Pediatric Praziquantel Consortium aims to submit the regulatory dossier for marketing approval in endemic countries and WHO prequalification in 2018/19 with approval and product launch for schistosomiasis pediatric case management in key endemic countries in 2019.Ultimately,the goal is for the product to be considered for a large-scale mass distribution program by 2022.