Bayesian spatial analysis of a national urinary schistosomiasis questionnaire to assist geographic targeting of schistosomiasis control in Tanzania, East Africa

Spatial modelling was applied to self-reported schistosomiasis data from over 2.5 million school students from 12,399 schools in all regions of mainland Tanzania. The aims were to derive statistically robust prevalence estimates in small geographical units (wards), to identify spatial clusters of high and low prevalence and to quantify uncertainty surrounding prevalence estimates. The objective was to permit informed decision-making for targeting of resources by the Tanzanian national schistosomiasis control programme. Bayesian logistic regression models were constructed to investigate the risk of schistosomiasis in each ward, based on the prevalence of self-reported schistosomiasis and blood in urine. Models contained covariates representing climatic and demographic effects and random effects for spatial clustering. Degree of urbanisation, median elevation of the ward and median normalised difference vegetation index (NDVI) were significantly and negatively associated with schistosomiasis prevalence. Most regions contained wards that had >95% certainty of schistosomiasis prevalence being >10%, the selected threshold for bi-annual mass chemotherapy of school-age children. Wards with >95% certainty of schistosomiasis prevalence being >30%, the selected threshold for annual mass chemotherapy of school-age children, were clustered in north-western, south-western and south-eastern regions. Large sample sizes in most wards meant raw prevalence estimates were robust. However, when uncertainties were investigated, intervention status was equivocal in 6.7-13.0% of wards depending on the criterion used. The resulting maps are being used to plan the distribution of praziquantel to participating districts; they will be applied to prioritising control in those wards where prevalence was unequivocally above thresholds for intervention and might direct decision-makers to obtain more information in wards where intervention status was uncertain.     

Potential Cost-Effectiveness of Schistosomiasis Treatment for Reducing HIV Transmission in Africa – The Case of Zimbabwean Women

Background

Epidemiological data from Zimbabwe suggests that genital infection with Schistosoma haematobium may increase the risk of HIV infection in young women. Therefore, the treatment of Schistosoma haematobium with praziquantel could be a potential strategy for reducing HIV infection. Here we assess the potential cost-effectiveness of praziquantel as a novel intervention strategy against HIV infection.

Methods

We developed a mathematical model of female genital schistosomiasis (FGS) and HIV infections in Zimbabwe that we fitted to cross-sectional data of FGS and HIV prevalence of 1999. We validated our epidemic projections using antenatal clinic data on HIV prevalence. We simulated annual praziquantel administration to school-age children. We then used these model predictions to perform a cost-effectiveness analysis of annual administration of praziquantel as a potential measure to reduce the burden of HIV in sub-Saharan Africa.

Findings

We showed that for a variation of efficacy between 30–70% of mass praziquantel administration for reducing the enhanced risk of HIV transmission per sexual act due to FGS, annual administration of praziquantel to school-age children in Zimbabwe could result in net savings of US$16–101 million compared with no mass treatment of schistosomiasis over a ten-year period. For a variation in efficacy between 30–70% of mass praziquantel administration for reducing the acquisition of FGS, annual administration of praziquantel to school-age children could result in net savings of US$36−92 million over a ten-year period.

Conclusions

In addition to reducing schistosomiasis burden, mass praziquantel administration may be a highly cost-effective way of reducing HIV infections in sub-Saharan Africa. Program costs per case of HIV averted are similar to, and under some conditions much better than, other interventions that are currently implemented in Africa to reduce HIV transmission. As a cost-saving strategy, mass praziquantel administration should be prioritized over other less cost-effective public health interventions.     

Delayed diagnosis of spinal cord schistosomiasis in a non-endemic country: A tertiary referral centre experience

BackgroundNeuroschistosomiasis is a severe complication of schistosomiasis, triggered by the local immune reaction to egg deposition, with spinal cord involvement the most well recognised form. Early treatment with praziquantel and high dose steroids leads to a reduction of neurological sequelae. The rarity of this condition in returning travellers to high income countries can result in delayed diagnosis and treatment. We aimed to evaluate the diagnosis and management of neuroschistosomiasis in a UK national referral centre.Materials/MethodsA retrospective review of confirmed clinical cases of spinal schistosomiasis referred to the Hospital for Tropical Diseases, UK, between January 2016 and January 2020 was undertaken. Electronic referral records were interrogated and patient demographic, clinical, laboratory, and radiological data collected.ResultsFour cases of neuroschistosomiasis were identified. The median age at diagnosis was 28 (range 21 to 50) with three male patients. All patients had epidemiological risk factors for schistosomiasis based on travel history and freshwater exposure; two in Uganda (River Nile), one in Malawi and one in Nigeria. All patients presented with features of transverse myelitis including back pain, leg weakness, paraesthesia and urinary dysfunction. The mean time from presentation to health services to definitive treatment was 42.5 days (range 16–74 days). Diagnosis was confirmed with CSF serology for schistosomiasis in all cases. Radiological features on MRI spine included enhancement focused predominantly in the lower thoracic spinal cord in three cases and the conus in one patient. All patients received a minimum of three days of oral praziquantel and high dose steroids. At three-month follow-up, one patient had complete resolution of symptoms and three had residual deficit; one patient was left with urinary and faecal incontinence, another had urinary retention, and the final patient has persistent leg pains and constipation.ConclusionWe observed a marked delay in diagnosis of neuroschistosomiasis in a non-endemic country. We advocate undertaking a thorough travel history, early use of imaging and CSF schistosomal serology to ensure early diagnosis of neuroschistosomiasis in patients presenting with consistent symptoms. If schistosomal diagnostics are not immediately available, presumptive treatment under the guidance of a tropical medicine specialist should be considered to minimize the risk of residual disability. We advocate for consensus guidelines to be produced and reporting to be performed in a uniform way for patients with spinal schistosomiasis.     

Praziquantel,Mefloquine-Praziquantel,and Mefloquine-Artesunate-Praziquantel against Schistosoma haematobium: A Randomized,Exploratory, Open-Label Trial

Background

Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel. Hence, there is a pressing need to develop additional therapeutics against schistosomiasis. The antimalarial drug mefloquine shows antischistosomal activity in animal models and clinical trials, which calls for further investigations.

Methodology

We comparatively assessed the efficacy and tolerability of the following treatments against Schistosoma haematobium in school-aged children in Côte d''Ivoire: (i) praziquantel (40 mg/kg; standard treatment); (ii) mefloquine (25 mg/kg) combined with praziquantel (40 mg/kg); and (iii) mefloquine-artesunate (3× (100 mg artesunate +250 mg mefloquine)) combined with praziquantel (40 mg/kg) (treatments administered on subsequent days). Two urine samples were collected before, and on days 21–22 and 78–79 after the first dosing.

Principal Findings

Sixty-one children were present on all examination time points and had complete datasets. No difference in efficacy was observed between the three treatment groups on either follow-up. On the 21–22 day posttreatment follow-up, based on available case analysis, cure rates of 33% (95% confidence interval (CI) 11–55%), 29% (95% CI 8–50%), and 26% (95% CI 5–48%) were observed for praziquantel, mefloquine-artesunate-praziquantel, and mefloquine-praziquantel, respectively. The corresponding egg reduction rates were 94% and above. On the second follow-up, observed cure rates ranged from 19% (praziquantel) to 33% (mefloquine-artesunate-praziquantel), and egg reduction rates were above 90%. Praziquantel monotherapy was the best tolerated treatment. In the mefloquine-artesunate-praziquantel group, adverse events were reported by 91% of the participants, and in the mefloquine-praziquantel group, 95% experienced adverse events. With the exception of abdominal pain at moderate severity, adverse events were mild.

Conclusions/Significance

The addition of mefloquine or mefloquine-artesunate does not increase the efficacy of praziquantel against chronic S. haematobium infection. Additional studies are necessary to elucidate the effect of the combinations against acute schistosomiasis.     

Determining Treatment Needs at Different Spatial Scales Using Geostatistical Model-Based Risk Estimates of Schistosomiasis

Background

After many years of neglect, schistosomiasis control is going to scale. The strategy of choice is preventive chemotherapy, that is the repeated large-scale administration of praziquantel (a safe and highly efficacious drug) to at-risk populations. The frequency of praziquantel administration is based on endemicity, which usually is defined by prevalence data summarized at an arbitrarily chosen administrative level.

Methodology

For an ensemble of 29 West and East African countries, we determined the annualized praziquantel treatment needs for the school-aged population, adhering to World Health Organization guidelines. Different administrative levels of prevalence aggregation were considered; country, province, district, and pixel level. Previously published results on spatially explicit schistosomiasis risk in the selected countries were employed to classify each area into distinct endemicity classes that govern the frequency of praziquantel administration.

Principal Findings

Estimates of infection prevalence adjusted for the school-aged population in 2010 revealed that most countries are classified as moderately endemic for schistosomiasis (prevalence 10–50%), while four countries (i.e., Ghana, Liberia, Mozambique, and Sierra Leone) are highly endemic (>50%). Overall, 72.7 million annualized praziquantel treatments (50% confidence interval (CI): 68.8–100.7 million) are required for the school-aged population if country-level schistosomiasis prevalence estimates are considered, and 81.5 million treatments (50% CI: 67.3–107.5 million) if estimation is based on a more refined spatial scale at the provincial level.

Conclusions/Significance

Praziquantel treatment needs may be over- or underestimated depending on the level of spatial aggregation. The distribution of schistosomiasis in Ethiopia, Liberia, Mauritania, Uganda, and Zambia is rather uniform, and hence country-level risk estimates are sufficient to calculate treatment needs. On the other hand, countries like Burkina Faso, Mali, Mozambique, Sudan, and Tanzania show large spatial heterogeneity in schistosomiasis risk, which should be taken into account for calculating treatment requirements.     

Triple co-administration of ivermectin, albendazole and praziquantel in zanzibar: a safety study

Background

Public health interventions based on distribution of anthelminthic drugs against lymphatic filariasis (LF), onchocerciasis, soil-transmitted helminthiasis (STH) and schistosomiasis have been implemented separately to date. A better use of available resources might be facilitated by a more coordinated approach to control such infections, including the possibility of co-administering the three recommended anthelminthic drugs through a single, large-scale intervention.

Methodology/Principal Findings

Ivermectin, albendazole and praziquantel were co-administered to 5,055 children and adults living in areas endemic for LF, STH and schistosomiasis in Zanzibar, United Republic of Tanzania, during a pilot intervention aimed at elucidating and quantifying possible side-effects. Subsequently, these drugs were co-administered to about 700,000 individuals during a countrywide intervention targeting a large part of the total population of Zanzibar. Passive and active surveillance measures carried out during both interventions showed that side-effects attributable to the three drugs given at the same time were mild and self-limiting events.

Conclusions/Significance

Our data suggest that co-administration of ivermectin, albendazole and praziquantel is safe in areas where lymphatic filariasis, soil-transmitted helminthiasis and schistosomiasis are co-endemic and where several rounds of treatment with one or two drugs have been implemented in the past. Passive surveillance measures, however, should be continued and detection, management and reporting of possible side-effects should be considered a key component of any health intervention administering drugs.     

The USAID/Government of Egypt's Schistosomiasis Research Project (SRP)

Schistosomiasis is the major public health problem in rural Egypt, with almost six million Egyptians infected as at mid-1996. In 1983, the prevalence of schistosomiasis in rural Egypt was greater than 50%, but a ten-year campaign of diagnosis and treatment has reduced the prevalence and intensity of infection. Parallel to this campaign, the government of the USA has funded a research project to examine all aspects of schistosomiasis with a view to improving the control strategy. As outlined here by Taha El Khoby, Nabil Galal and Alan Fenwick, after almost ten years, the project's achievements include: assisting WHO in its attempts to develop a vaccine against schistosomiasis, developing a suspension formulation of praziquantel suitable for young children, and establishing a unit to monitor reports of resistance to praziquantel. In addition, a large epidemiological study has established the extent of the problem in Egypt. Slow-release formulation of niclosamide, health education material for use on TV, dipstick diagnostic tests, and evaluation of ultrasound as a diagnostic tool have also been achieved. As the project closes, Egypt is left with an effective strategy for the control of schistosomiasis and several back-up tools for use in the event of development of resistance to praziquantel. The Ministry of Health and Population has the basis of a Geographical Information System (GIS) unit and the country has a trained and equipped scientific community capable of biomedical research, and almost 100 scientific papers published on their work.     

Effects of repeated praziquantel treatment on schistosomiasis mekongi morbidity as detected by ultrasonography

Schistosomiasis mekongi is endemic in the Mekong River basin; about 80,000 people are at risk of infection in Cambodia. We conducted ultrasonographic studies of patients with schistosomiasis mekongi in Kratie province, Cambodia, focusing especially on the relationship between the frequency of praziquantel treatment and findings of ultrasonographic imaging. The frequency of praziquantel treatment in the period from 1995 to 2002 was classified into four groups: 1–2, 3–4, 5–6, and 7–8 times. Ultrasonographic images were examined to determine the presence of thickening of the portal vein wall and formation of meandering collateral circulation of the splenic vein. We selected these parameters because they are unaffected by interobserver bias. The results showed that thickening of the portal vein wall may have potential to improve with frequent praziquantel treatment. On the other hand, established hard splenomegaly and meandering collateral circulation of the splenic vein, improved very little with praziquantel treatment.     

Schistosomiasis control: keep taking the tablets

Despite the limited reports of praziquantel resistance, the relative success of chemotherapy-based control programmes for schistosomiasis has prompted overdue efforts to expand the use of cheap, generic, praziquantel in sub-Saharan Africa. The likely impact of such programmes on the development and spread of praziquantel resistance is uncertain, but this possibility reinforces the need for monitoring the spectrum of praziquantel sensitivity of schistosome populations and for an improved knowledge of the precise targets for the action of the drug. The search for alternatives to praziquantel and other tools for control of schistosomiasis must continue.     

Performance and Safety of Praziquantel for Treatment of Intestinal Schistosomiasis in Infants and Preschool Children

Background

In 2012 the WHO formally recognised that infants and preschool children are at significant risk of schistosomiasis and qualify for treatment with praziquantel (PZQ). Targeted surveys determining both the performance and safety of this drug are now needed in endemic areas. We have formally assessed parasitological cure and putative side-effects in a prospective cohort of Schistosoma mansoni-infected children (aged 5 months–7 years old) in lakeshore settings of Uganda.

Methodology/Principal Findings

From a total of 369 children found to be egg-patent for intestinal schistosomiasis, 305 were followed-up three to four weeks after PZQ treatment and infection status re-assessed. Separately, a previously tested side-effect questionnaire was employed before and 24 hours after PZQ treatment to assess incidence and amelioration of symptoms in young children and their mothers. While the overall observed parasitological cure was 56.4%, a significant difference was found between a sub-set of children who had a history of multiple PZQ treatments (between one and four in an 18 month period), where cure rate was 41.7%, and those who had never received treatment (cure rate was 77·6%). PZQ proved to be safe, with only mild reported side effects which cleared within a month after treatment. Prevalence of reported symptoms was significantly lower in children than in mothers, and fewer side-effects were reported upon subsequent rounds of PZQ treatment.

Conclusion/Significance

Our findings show that PZQ treatment of young children resulted in satisfactory cure rates, and marked reduction in egg-output, with only mild and transient reported side-effects. However, the cure rate is clearly lower in younger children and those with history of previous treatment. Cure rate, but not egg reduction rate, was also lower in children with heavier pre-intervention infection intensity. With chemotherapy now recommended as a long-term strategy for disease control in young children, research into optimising the periodicity of targeted treatment strategies is now crucial.     

Human schistosomiasis and anemia: the relationship and potential mechanisms

Although many cross-sectional studies and a small number of randomized controlled trials have addressed the relationship between schistosomiasis and anemia, the conflicting results make the magnitude of the relationship unclear. In fact, only one randomized controlled trial that treated solely for schistosomiasis has demonstrated an impact of praziquantel on hemoglobin concentration. The potential mechanisms underlying a relationship between schistosomiasis and anemia are also unclear. In this article, we discuss four possible mechanisms that might mediate this relationship, based on animal and human models, including extra-corporeal loss of iron, splenomegaly leading to red blood cell sequestration, autoimmune hemolysis and anemia of inflammation.     

Bayesian Risk Mapping and Model-Based Estimation of Schistosoma haematobium–Schistosoma mansoni Co-distribution in C?te d′Ivoire

Background

Schistosoma haematobium and Schistosoma mansoni are blood flukes that cause urogenital and intestinal schistosomiasis, respectively. In Côte d′Ivoire, both species are endemic and control efforts are being scaled up. Accurate knowledge of the geographical distribution, including delineation of high-risk areas, is a central feature for spatial targeting of interventions. Thus far, model-based predictive risk mapping of schistosomiasis has relied on historical data of separate parasite species.

Methodology

We analyzed data pertaining to Schistosoma infection among school-aged children obtained from a national, cross-sectional survey conducted between November 2011 and February 2012. More than 5,000 children in 92 schools across Côte d′Ivoire participated. Bayesian geostatistical multinomial models were developed to assess infection risk, including S. haematobium–S. mansoni co-infection. The predicted risk of schistosomiasis was utilized to estimate the number of children that need preventive chemotherapy with praziquantel according to World Health Organization guidelines.

Principal Findings

We estimated that 8.9% of school-aged children in Côte d′Ivoire are affected by schistosomiasis; 5.3% with S. haematobium and 3.8% with S. mansoni. Approximately 2 million annualized praziquantel treatments would be required for preventive chemotherapy at health districts level. The distinct spatial patterns of S. haematobium and S. mansoni imply that co-infection is of little importance across the country.

Conclusions/Significance

We provide a comprehensive analysis of the spatial distribution of schistosomiasis risk among school-aged children in Côte d′Ivoire and a strong empirical basis for a rational targeting of control interventions.     

Reduction in the prevalence and intensity of hookworm infections after praziquantel treatment for schistosomiasis infection

Praziquantel exhibits activity against all major human schistosome parasites and has become the cornerstone for treatment and morbidity control of schistosomiasis. Praziquantel is also active against a wide range of trematodes, human and veterinary cestodes and displays cysticidal effects. To the best of our knowledge anthelminthic properties have never been documented. Here, we report a study among 96 schoolchildren from an area highly endemic for Schistosoma mansoni and hookworm infection, and place particular emphasis on the effect of praziquantel on the prevalence and intensity of hookworm infections. Stool specimens were screened over several consecutive days prior and 4 weeks after systematic administration of praziquantel. We found a significant reduction in the prevalence of hookworm infection from 75.0 to 40.6% (odds ratio (OR)=0.21; 95% confidence interval (CI): 0.11-0.40). Infection intensities, expressed by geometric mean egg counts of all children, were also reduced significantly from 10.7 to 2.0 eggs per gram stool (paired t-test=7.78, P<0.001). If these findings are confirmed in other epidemiological settings - following a similarly sensitive diagnostic approach - they might become of considerable relevance. In areas where both schistosome and hookworm coexist, and praziquantel is being recommended for schistosomiasis control, large-scale application of this drug might also reduce the burden of hookworms.     

Field survey for strongyloidiasis in eastern Uganda with observations on efficacy of preventive chemotherapy and co-occurrence of soil-transmitted helminthiasis/intestinal schistosomiasis

Following our previous field surveys for strongyloidiasis in western Uganda, 120 mothers and 232 children from four villages in eastern Uganda were examined, with two subsequent investigative follow-ups. As before, a variety of diagnostic methods were used: Baermann concentration, Koga agar plate and strongyloidid enzyme-linked immunosorbent assay (ELISA), as well as Kato-Katz faecal smears for detection of eggs of other helminths. At baseline, the general prevalence of Strongyloides stercoralis was moderate: 5.4% as estimated by Baermann and Koga agar methods combined. A much higher estimate was found by ELISA (42.3%) which, in this eastern setting, appeared to be confounded by putative cross-reaction(s) with other nematode infections. Preventive chemotherapy using praziquantel and albendazole was offered to all participants at baseline. After 21 days the first follow-up was conducted and 'cure rates' were calculated for all parasites encountered. Eleven months later, the second follow-up assessed longer-term trends. Initial treatments had little, if any, effect on S. stercoralis, and did not alter local prevalence, unlike hookworm infections and intestinal schistosomiasis. We propose that geographical patterns of strongyloidiasis are likely not perturbed by ongoing praziquantel/albendazole campaigns. Antibody titres increased after the first follow-up then regressed towards baseline levels upon second inspection. To better define endemic areas for S. stercoralis, careful interpretation of the ELISA is warranted, especially where diagnosis is likely being confounded by polyparasitism and/or other treatment regimens; new molecular screening tools are clearly needed.     

Screening for schistosomiasis with questionnaires

New schistosomiasis control initiatives have been launched to reduce significantly the current global burden of this disease, mainly through regular administration of praziquantel to schoolchildren living in endemic areas. Because schistosomiasis is distributed focally, epidemiological tools for rapid and inexpensive identification of communities at highest risk of morbidity are required to target praziquantel most efficiently. This article outlines the development and validation of simple questionnaires for screening of Schistosoma haematobium and Schistosoma mansoni in sub-Saharan Africa.     

Schistosoma mansoni infection induces plasmablast and plasma cell death in the bone marrow and accelerates the decline of host vaccine responses

Schistosomiasis is a potentially lethal parasitic disease that profoundly impacts systemic immune function in chronically infected hosts through mechanisms that remain unknown. Given the immunoregulatory dysregulation experienced in infected individuals, this study examined the impact of chronic schistosomiasis on the sustainability of vaccine-induced immunity in both children living in endemic areas and experimental infections in mice. Data show that chronic Schistosoma mansoni infection impaired the persistence of vaccine specific antibody responses in poliovirus-vaccinated humans and mice. Mechanistically, schistosomiasis primarily fostered plasmablast and plasma cell death in the bone marrow and removal of parasites following praziquantel treatment reversed the observed cell death and partially restored vaccine-induced memory responses associated with increased serum anti-polio antibody responses. Our findings strongly suggest a previously unrecognized mechanism to explain how chronic schistosomiasis interferes with an otherwise effective vaccine regimen and further advocates for therapeutic intervention strategies that reduce schistosomiasis burden in endemic areas prior to vaccination.     

Towards control of schistosomiasis in sub-Saharan Africa

Approximately 80% of the 200 million people infected with schistosomiasis inhabit sub-Saharan Africa, and the annual mortality is estimated to be 280,000. Praziquantel is the drug of choice in the treatment of schistosomiasis and pregnant women may now be treated. It was agreed at the World Health Assembly in 2001 that at least 75% of school-aged children in high burden areas should be treated for schistosomiasis and soil-transmitted helminth infections by 2010 to reduce morbidity. A grant from the Bill and Melinda Gates Foundation to the Schistosomiasis Control Initiative, Imperial College of Science, Technology and Medicine, London has enabled control programmes to be initiated in Uganda, Tanzania, Zambia, Burkina Faso, Niger and Mali. Additional programmes have recently commenced in Zanzibar with a grant from the Health Foundation to The Natural History Museum, London and in Cameroon. Combination treatment for schistosomiasis, gastrointestinal helminths and filariasis reduces costs of control programmes. The EC Concerted Action Group on 'Praziquantel: its central role in the chemotherapy of schistosome infection' met in Yaoundé Cameroon in 2004 to discuss recent developments in laboratory and field studies. The use of standard operating procedures will enable data on drug action on schistosomes produced in different laboratories to be compared. With the ever increasing use of praziquantel there is a possibility of the development of resistance by schistosomes to the drug, hence the necessity to explore the activities of other compounds. Artemether, unlike praziquantel, is effective against immature schistosomes. The effectiveness of mirazid, an extract of myrrh, is controversial as data from different laboratories are equivocal. It is suggested that an independent body such as the World Health Organization should determine whether mirazid should be used in the treatment of schistosomiasis.     

Efficacy and Safety of Praziquantel in Preschool-Aged Children in an Area Co-Endemic for Schistosoma mansoni and S. haematobium

Background

In sub-Saharan Africa the recommended strategy to control schistosomiasis is preventive chemotherapy. Emphasis is placed on school-aged children, but in high endemicity areas, preschool-aged children are also at risk, and hence might need treatment with praziquantel. Since a pediatric formulation (e.g., syrup) is not available outside of Egypt, crushed praziquantel tablets are used, but the efficacy and safety of this treatment regimen is insufficiently studied.

Methodology

We assessed the efficacy and safety of crushed praziquantel tablets among preschool-aged children (<6 years) in the Azaguié district, south Côte d''Ivoire, where Schistosoma mansoni and S. haematobium coexist. Using a cross-sectional design, children provided two stool and two urine samples before and 3 weeks after treatment. Crushed praziquantel tablets, mixed with water, were administered at a dose of 40 mg/kg. Adverse events were assessed and graded 4 and 24 hours posttreatment by interviewing mothers/guardians.

Principal Findings

Overall, 160 preschool-aged children had at least one stool and one urine sample examined with duplicate Kato-Katz thick smears and a point-of-care circulating cathodic antigen (POC-CCA) cassette for S. mansoni, and urine filtration for S. haematobium diagnosis before and 3 weeks after praziquantel administration. According to the Kato-Katz and urine filtration results, we found high efficacy against S. mansoni (cure rate (CR), 88.6%; egg reduction rate (ERR), 96.7%) and S. haematobium (CR, 88.9%; ERR, 98.0%). POC-CCA revealed considerably lower efficacy against S. mansoni (CR, 53.8%). Treatment was generally well tolerated, but moderately severe adverse events (i.e., body and face inflammation), were observed in four Schistosoma egg-negative children.

Conclusions/Significance

Crushed praziquantel administered to preschool-aged children at a dose of 40 mg/kg is efficacious against S. mansoni and S. haematobium in a co-endemic setting of Côte d''Ivoire. Further research is required with highly sensitive diagnostic tools and safety must be investigated in more depth.

Trial Registration

Controlled-Trials.com ISRCTN53172722     

New insight into the antifibrotic effects of praziquantel on mice in infection with Schistosoma japonicum

Background

Schistosomiasis is a parasitic disease infecting more than 200 million people in the world. Although chemotherapy targeting on killing schistosomes is one of the main strategies in the disease control, there are few effective ways of dealing with liver fibrosis caused by the parasite infection in the chronic and advanced stages of schistosomiasis. For this reason, new strategies and prospective drugs, which exert antifibrotic effects, are urgently required.

Methods and Findings

The antifibrotic effects of praziquantel were assessed in the murine models of schistosomiasis japonica. Murine fibrosis models were established by cutaneous infection with 14±2 Schistosoma japonicum cercariae. Then, the mice of both chronic (8 weeks post-infection) and advanced (15 weeks post-infection) schistosomiasis were treated by gavage of praziquantel (250 mg/kg, once daily for 3 days) to eliminate worms, and followed by praziquantel anti-fibrosis treatment (300 mg/kg, twice daily for 30 days). The fibrosis-related parameters assessed were areas of collagen deposition, content of hydroxyproline and mRNA expressions of Col1α1, Col3α1, α-SMA, TGF-β, MMP9, TIMP1, IL-4, IL-10, IL-13 and IFN-γ of liver. Spleen weight index, alanine aminotransferase activity and liver portal venous pressure were also measured. The results showed that anti-fibrosis treatment improved liver fibrosis, splenomegaly, hepatic function, as well as liver portal hypertension. In order to confirm the anti-fibrotic properties of praziquantel, we established a CCL₄-induced model and revealed that CCL₄-induced liver fibrosis was inhibited by PZQ treatment for 30 days. Furthermore, we analyzed the effects of praziquantel on mouse primary hepatic stellate cells (HSCs). It is indicated that mRNA expressions of Col1α1, Col3α1, α-SMA, TGF-β, MMP9 and TIMP1 of HSCs were all inhibited after praziquantel anti-parasite treatments.

Conclusions

The significant amelioration of hepatic fibrosis by praziquantel treatment validates it as a promising drug of anti-fibrosis and offers potential of a new chemotherapy for hepatic fibrosis resulting from schistosomiasis.     

Schistosome resistance to praziquantel: Fact or artifact?

Praziquantel is the current drug of choice for human schistosomiasis. Recent reports from laboratory and field studies concerning reduced praziquantel efficacy against Schistosoma mansoni have generated some controversy. The prevailing question is whether the emergence of strains of schistosome resistant to praziquantel is a fact, or an artifact resulting from erroneous field or laboratory experimentation. In this article, Padraic Fallon, Liang-feng Tao, Magdi Ismail and James Bennett examine the available evidence for schistosome resistance to praziquantel. Contributory factors to the schistosomicidal activity of praziquantel, which may interfere with evaluation of drug efficacy or resistance, are also considered.