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PLoS Neglected Tropical Diseases Feb 2017Since 1984, WHO has endorsed drug treatment to reduce Schistosoma infection and its consequent morbidity. Cross-sectional studies suggest pre-treatment correlation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Since 1984, WHO has endorsed drug treatment to reduce Schistosoma infection and its consequent morbidity. Cross-sectional studies suggest pre-treatment correlation between infection intensity and risk for Schistosoma-related pathology. However, evidence also suggests that post-treatment reduction in intensity may not reverse morbidity because some morbidities occur at all levels of infection, and some reflect permanent tissue damage. The aim of this project was to systematically review evidence on drug-based control of schistosomiasis and to develop a quantitative estimate of the impact of post-treatment reductions in infection intensity on prevalence of infection-associated morbidity.
METHODOLOGY/PRINCIPAL FINDINGS
This review was registered at inception with PROSPERO (CRD42015026080). Studies that evaluated morbidity before and after treatment were identified by online searches and searches of private archives. Post-treatment odds ratios or standardized mean differences were calculated for each outcome, and these were correlated to treatment-related egg count reduction ratios (ERRs) by meta-regression. A greater ERR correlated with greater reduction in odds of most morbidities. Random effects meta-analysis was used to derive summary estimates: after treatment of S. mansoni and S. japonicum, left-sided hepatomegaly was reduced by 54%, right-sided hepatomegaly by 47%, splenomegaly by 37%, periportal fibrosis by 52%, diarrhea by 53%, and blood in stools by 75%. For S. haematobium, hematuria was reduced by 92%, proteinuria by 90%, bladder lesions by 86%, and upper urinary tract lesions by 72%. There were no consistent changes in portal dilation or hemoglobin levels. In sub-group analysis, age, infection status, region, parasite species, and interval to follow-up were associated with meaningful differences in outcome.
CONCLUSION/SIGNIFICANCE
While there are challenges to implementing therapy for schistosomiasis, and praziquantel therapy is not fully curative, reductions in egg output are significantly correlated with decreased morbidity and can be used to project diminution in disease burden when contemplating more aggressive strategies to minimize infection intensity.
Topics: Animals; Anthelmintics; Humans; Praziquantel; Schistosoma; Schistosomiasis
PubMed: 28212414
DOI: 10.1371/journal.pntd.0005372 -
PLoS Neglected Tropical Diseases Jun 2016Schistosomiasis control mainly relies on preventive chemotherapy with praziquantel (PZQ) distributed through mass drug administration. With a target of 260 million... (Review)
Review
The Schistosomiasis Clinical Trials Landscape: A Systematic Review of Antischistosomal Treatment Efficacy Studies and a Case for Sharing Individual Participant-Level Data (IPD).
BACKGROUND
Schistosomiasis control mainly relies on preventive chemotherapy with praziquantel (PZQ) distributed through mass drug administration. With a target of 260 million treatments yearly, reliably assessing and monitoring efficacy is all-important. Recommendations for treatment and control of schistosomiasis are supported by systematic reviews and meta-analyses of aggregated data, which however also point to limitations due to heterogeneity in trial design, analyses and reporting. Some such limitations could be corrected through access to individual participant-level data (IPD), which facilitates standardised analyses.
METHODOLOGY
A systematic literature review was conducted to identify antischistosomal drug efficacy studies performed since 2000; including electronic searches of the Cochrane Infectious Diseases Group specialised register and the Cochrane Library, PubMed, CENTRAL and Embase; complemented with a manual search for articles listed in past reviews. Antischistosomal treatment studies with assessment of outcome within 60 days post-treatment were eligible. Meta-data, i.e. study-level characteristics (Schistosoma species, number of patients, drug administered, country, etc.) and efficacy parameters were extracted from published documents to evaluate the scope of an individual-level data sharing platform.
PRINCIPAL FINDINGS
Out of 914 documents screened, 90 studies from 26 countries were included, enrolling 20,517 participants infected with Schistosoma spp. and treated with different PZQ regimens or other drugs. Methodologies varied in terms of diagnostic approaches (number of samples and test repeats), time of outcome assessment, and outcome measure (cure rate or egg reduction rate, as an arithmetic or geometric mean), making direct comparison of published data difficult.
CONCLUSIONS
This review describes the landscape of schistosomiasis clinical research. The volume of data and the methodological and reporting heterogeneity identified all indicate that there is scope for an individual participant-level database, to allow for standardised analyses.
Topics: Anthelmintics; Data Interpretation, Statistical; Humans; Randomized Controlled Trials as Topic; Schistosomiasis
PubMed: 27347678
DOI: 10.1371/journal.pntd.0004784 -
Parasitology Research Aug 2016Cystic echinococcosis (CE) is a widespread zoonosis caused by the species complex Echinococcus granulosus. Albendazole (ABZ)-the first-line anthelminthic drug for...
Cystic echinococcosis (CE) is a widespread zoonosis caused by the species complex Echinococcus granulosus. Albendazole (ABZ)-the first-line anthelminthic drug for medical treatment of CE-is metabolized in vivo to the active derivative ABZ-sulphoxide (ABZ-SO). Target-site ABZ-SO concentrations in the hydatid cyst mediate the anthelminthic effect in CE. Primary outcome of this systematic review of individual patient data was the intra-cystic ABZ-SO concentration stratified by cyst size, location, calcification status and use of praziquantel. Studies reporting intra-cystic ABZ-SO concentrations in humans were identified by a systematic search. A pooled analysis of individual patient data was performed to assess intra-cystic concentrations. Pharmacokinetic data of 121 individual cysts were analysed. There was no correlation between plasma and intra-cystic ABZ-SO concentrations (rho = -0.03, p = 0.76). Intra-cystic drug concentrations were also not associated with sex and treatment duration. Use of praziquantel in combination with ABZ was associated with higher plasma (median 540 vs. 240 μg/L; p = 0.04) but not intra-cystic ABZ-SO concentrations (median 220 vs. 199 μg/L; p = 0.36). Relative drug concentrations in hepatic cysts were higher than in other cysts (0.8 vs. 0.4; p = 0.05). Intra-cystic concentrations were higher in calcified than non-calcified cysts (median 897 vs. 245 μg/L; p = 0.03). There was a trend towards higher intra-cystic concentrations in smaller sized cysts (β = -17.2 μg/L/cm; 95th CI, -35.9 to 1.6; p = 0.07). This study demonstrates that mean intra-cystic drug concentrations are similar to plasma concentrations on a population level. However, in individual patients plasma concentrations are not directly predictive for intra-cystic concentrations. The use of booster drugs was not associated with higher intra-cystic ABZ-SO concentrations in this analysis.
Topics: Albendazole; Animals; Anthelmintics; Cysts; Echinococcosis; Echinococcus granulosus; Humans; Praziquantel
PubMed: 27085708
DOI: 10.1007/s00436-016-5054-x -
The Cochrane Database of Systematic... Apr 2016Helminth infections, such as soil-transmitted helminths, schistosomiasis, onchocerciasis, and lymphatic filariasis, are prevalent in many countries where human... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Helminth infections, such as soil-transmitted helminths, schistosomiasis, onchocerciasis, and lymphatic filariasis, are prevalent in many countries where human immunodeficiency virus (HIV) infection is also common. There is some evidence from observational studies that HIV and helminth co-infection may be associated with higher viral load and lower CD4+ cell counts. Treatment of helminth infections with antihelminthics (deworming drugs) may have benefits for people living with HIV beyond simply clearance of worm infections.This is an update of a Cochrane Review published in 2009 and we have expanded it to include outcomes of anaemia and adverse events.
OBJECTIVES
To evaluate the effects of deworming drugs (antihelminthic therapy) on markers of HIV disease progression, anaemia, and adverse events in children and adults.
SEARCH METHODS
In this review update, we searched online for published and unpublished studies in the Cochrane Library, MEDLINE, EMBASE, CENTRAL, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICRTP), ClinicalTrials.gov, and the WHO Global Health Library up to 29 September 2015. We also searched databases listing conference abstracts, scanned reference lists of articles, and contacted the authors of included studies.
SELECTION CRITERIA
We searched for randomized controlled trials (RCTs) that compared antihelminthic drugs with placebo or no intervention in HIV-positive people.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed trials for eligibility and risk of bias. The primary outcomes were changes in HIV viral load and CD4+ cell count, and secondary outcomes were anaemia, iron deficiency, adverse events, and mortality events. We compared the effects of deworming using mean differences, risk ratios (RR), and 95% confidence intervals (CIs). We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
Eight trials met the inclusion criteria of this review, enrolling a total of 1612 participants. Three trials evaluated the effect of providing antihelminthics to all adults with HIV without knowledge of their helminth infection status, and five trials evaluated the effects of providing deworming drugs to HIV-positive individuals with confirmed helminth infections. Seven trials were conducted in sub-Saharan Africa and one in Thailand. Antihelminthics for people with unknown helminth infection statusProviding antihelminthics (albendazole and praziquantel together or separately) to HIV-positive adults with unknown helminth infection status may have a small suppressive effect on mean viral load at six weeks but the 95% CI includes the possibility of no effect (difference in mean change -0.14 log10 viral RNA/mL, 95% CI -0.35 to 0.07, P = 0.19; one trial, 166 participants, low quality evidence).Repeated dosing with deworming drugs over two years (albendazole every three months plus annual praziquantel), probably has little or no effect on mean viral load (difference in mean change 0.01 log10 viral RNA, 95% CI: -0.03 to -0.05; one trial, 917 participants, moderate quality evidence), and little or no effect on mean CD4+ count (difference in mean change 2.60 CD4+ cells/µL, 95% CI -10.15 to 15.35; P = 0.7; one trial, 917 participants, low quality evidence). Antihelminthics for people with confirmed helminth infectionsTreating confirmed helminth infections in HIV-positive adults may have a small suppressive effect on mean viral load at six to 12 weeks following deworming (difference in mean change -0.13 log10 viral RNA, 95% CI -0.26 to -0.00; P = 0.04; four trials, 445 participants, low quality evidence). However, this finding is strongly influenced by a single study of praziquantel treatment for schistosomiasis. There may also be a small favourable effect on mean CD4+ cell count at 12 weeks after deworming in HIV-positive populations with confirmed helminth infections (difference in mean change 37.86 CD4+ cells/µL, 95% CI 7.36 to 68.35; P = 0.01; three trials, 358 participants, low quality evidence). Adverse events and mortality There is no indication that antihelminthic drugs impart additional risks in HIV-positive populations. However, adverse events were not well reported (very low quality evidence) and trials were underpowered to evaluate effects on mortality (low quality evidence).
AUTHORS' CONCLUSIONS
There is low quality evidence that treating confirmed helminth infections in HIV-positive adults may have small, short-term favourable effects on markers of HIV disease progression. Further studies are required to confirm this finding. Current evidence suggests that deworming with antihelminthics is not harmful, and this is reassuring for the routine treatment of confirmed or suspected helminth infections in people living with HIV in co-endemic areas.Further long-term studies are required to make confident conclusions regarding the impact of presumptively deworming all HIV-positive individuals irrespective of helminth infection status, as the only long-term trial to date did not demonstrate an effect.
Topics: Adult; Anthelmintics; CD4 Lymphocyte Count; Disease Progression; Endemic Diseases; HIV Infections; HIV-1; Health Resources; Helminthiasis; Humans; Poverty Areas; RNA, Viral; Randomized Controlled Trials as Topic; Viral Load
PubMed: 27075622
DOI: 10.1002/14651858.CD006419.pub4 -
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 -
International Journal of Public Health Nov 2015Male genital schistosomiasis (MGS) is a neglected manifestation of Schistosoma haematobium infection with ignored implications on reproductive health and a differential...
OBJECTIVES
Male genital schistosomiasis (MGS) is a neglected manifestation of Schistosoma haematobium infection with ignored implications on reproductive health and a differential diagnosis to sexually transmitted infections in endemic regions. MGS may have associations with HIV transmission and acquisition, and treatment could be a neglected chance of HIV prevention. This review summarizes current knowledge on epidemiology, clinical manifestations, diagnosis and treatment of MGS as a hypothesized risk factor for HIV transmission. Future research areas of global interest are suggested.
METHODS
PubMed published literature was reviewed based on the MOOSE guidelines. All publications on MGS were included regardless of publication year and study design. Furthermore, all publications were searched for information on possible HIV association.
RESULTS
The 40 identified publications related to MGS were dominated by case reports and observational studies. No randomized clinical trials have been conducted to date, and very scant information related to possible associations with HIV transmission was presented.
CONCLUSIONS
Clinical, randomized studies and epidemiological studies covering the possible association between MGS and HIV are urgently needed. Furthermore, field diagnostic tools should be developed and future mass treatment programs should include adults to reduce morbidity and prevent HIV acquisition.
SYSTEMATIC REVIEW REGISTRATION NUMBER
CRD42015016252.
Topics: Adult; Animals; Endemic Diseases; HIV Infections; HIV-1; Humans; Male; Praziquantel; Risk Factors; Schistosoma haematobium; Schistosomiasis haematobia; Schistosomicides; Sexually Transmitted Diseases; Virus Shedding
PubMed: 26298443
DOI: 10.1007/s00038-015-0714-7 -
The Lancet. Infectious Diseases Aug 2015Schistosomiasis affects more than 200 million individuals, mostly in sub-Saharan Africa, but empirical estimates of the disease burden in this region are unavailable. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Schistosomiasis affects more than 200 million individuals, mostly in sub-Saharan Africa, but empirical estimates of the disease burden in this region are unavailable. We used geostatistical modelling to produce high-resolution risk estimates of infection with Schistosoma spp and of the number of doses of praziquantel treatment needed to prevent morbidity at different administrative levels in 44 countries.
METHODS
We did a systematic review to identify surveys including schistosomiasis prevalence data in sub-Saharan Africa via PubMed, ISI Web of Science, and African Journals Online, from inception to May 2, 2014, with no restriction of language, survey date, or study design. We used Bayesian geostatistical meta-analysis and rigorous variable selection to predict infection risk over a grid of 1 155 818 pixels at 5 × 5 km, on the basis of environmental and socioeconomic predictors and to calculate the number of doses of praziquantel needed for prevention of morbidity.
FINDINGS
The literature search identified Schistosoma haematobium and Schistosoma mansoni surveys done in, respectively, 9318 and 9140 unique locations. Infection risk decreased from 2000 onwards, yet estimates suggest that 163 million (95% Bayesian credible interval [CrI] 155 million to 172 million; 18·5%, 17·6-19·5) of the sub-Saharan African population was infected in 2012. Mozambique had the highest prevalence of schistosomiasis in school-aged children (52·8%, 95% CrI 48·7-57·8). Low-risk countries (prevalence among school-aged children lower than 10%) included Burundi, Equatorial Guinea, Eritrea, and Rwanda. The numbers of doses of praziquantel needed per year were estimated to be 123 million (95% CrI 121 million to 125 million) for school-aged children and 247 million (239 million to 256 million) for the entire population.
INTERPRETATION
Our results will inform policy makers about the number of treatments needed at different levels and will guide the spatial targeting of schistosomiasis control interventions.
FUNDING
European Research Council, China Scholarship Council, UBS Optimus Foundation, and Swiss National Science Foundation.
Topics: Adolescent; Africa South of the Sahara; Animals; Bayes Theorem; Child; Child, Preschool; Health Services Needs and Demand; Humans; Morbidity; Mozambique; Praziquantel; Prevalence; Schistosoma haematobium; Schistosoma mansoni; Schistosomiasis
PubMed: 26004859
DOI: 10.1016/S1473-3099(15)00066-3 -
Parasites & Vectors Mar 2015Schistosomiasis is a disease caused by infection with blood flukes of the genus Schistosoma. Transmission of, and exposure to, the parasite result from faecal or urinary... (Review)
Review
Schistosomiasis is a disease caused by infection with blood flukes of the genus Schistosoma. Transmission of, and exposure to, the parasite result from faecal or urinary contamination of freshwater containing intermediate host snails, and dermal contact with the same water. The World Health Assembly resolution 65.21 from May 2012 urges member states to eliminate schistosomiasis through preventive chemotherapy (i.e. periodic large-scale administration of the antischistosomal drug praziquantel to school-aged children and other high-risk groups), provision of water, sanitation and hygiene (WASH) and snail control. However, control measures focus almost exclusively on preventive chemotherapy, while only few studies made an attempt to determine the impact of upgraded access to safe water, adequate sanitation and good hygiene on schistosome transmission. We recently completed a systematic review and meta-analysis pertaining to WASH and schistosomiasis and found that people with safe water and adequate sanitation have significantly lower odds of a Schistosoma infection. Importantly though, the transmission of schistosomiasis is deeply entrenched in social-ecological systems, and hence is governed by setting-specific cultural and environmental factors that determine human behaviour and snail populations. Here, we provide a comprehensive review of the literature, which explores the transmission routes of schistosomes, particularly focussing on how these might be disrupted with WASH-related technologies and human behaviour. Additionally, future research directions in this area are highlighted.
Topics: Animals; Child; Fresh Water; Global Health; Humans; Hygiene; Male; Praziquantel; Sanitation; Schistosoma; Schistosomiasis; Snails; Water
PubMed: 25884172
DOI: 10.1186/s13071-015-0766-9 -
Transactions of the Royal Society of... Apr 2015An estimated 129 million people are infected with urogenital schistosomiasis in sub-Saharan Africa. Current control recommendations endorse mass administration of... (Review)
Review
An estimated 129 million people are infected with urogenital schistosomiasis in sub-Saharan Africa. Current control recommendations endorse mass administration of praziquantel. Health education is an important component of effective schistosomiasis prevention and control, but there has been limited research on its effectiveness. This paper reviews the effectiveness of health education as an intervention in the prevention and control of urogenital schistosomiasis in sub-Saharan Africa. The outcomes of interest were prevalence, incidence or transmission of schistosomiasis, behaviour change associated with infection, or changes in knowledge of the disease. The findings from this review suggest that health education has a beneficial impact on knowledge and understanding of schistosomiasis within the target groups. However, further research is needed due to the poor quality of the included studies.
Topics: Africa South of the Sahara; Animals; Anthelmintics; Health Education; Health Knowledge, Attitudes, Practice; Health Services Needs and Demand; Humans; Incidence; Praziquantel; Preventive Health Services; Randomized Controlled Trials as Topic; Schistosomiasis haematobia
PubMed: 25669840
DOI: 10.1093/trstmh/trv008 -
Iranian Red Crescent Medical Journal Oct 2014Praziquantel, an antischistosomal compound, is used as first-line drug for chemotherapy of Schistosoma japonicum since 1984. In this article, we conducted a systematic...
BACKGROUND
Praziquantel, an antischistosomal compound, is used as first-line drug for chemotherapy of Schistosoma japonicum since 1984. In this article, we conducted a systematic review and mete-analysis to evaluate the efficacy and safety of different dosages of praziquantel (PZQ) for treatment of Schistosoma japonicum.
EVIDENCE ACQUISITION
A number of six articles published in peer-reviewed journals before December 2012 were selected for analysis after searching the following literature databases: PubMed/Medline, the Chinese WanFang Literature Database, China National Knowledge Infrastructure (1994-2012.12), and the Chinese Biomedical Literature (1978-2012.12).
RESULTS
The meta-analyses showed that there is no statistically significant difference of the negative rate on the egg using 40 mg/kg compared to 60 mg/kg PZQ for S. japonicum treatment (RR 0.79, 95% CI 0.46 1.35; P < 0.39). The meta-analysis showed that there is no statistically significant difference of the side effects using 30 mg/kg compared with 40 mg/kg (RR 0.97, 95% CI 0.68 1.38; P = 0.87), 40 mg/kg compared with 60 mg/kg (RR 0.79, 95% CI 0.46 1.35; P = 0.39) and 50 mg/kg compared with 60 mg/kg (RR 0.89, 95% CI 0.56 1.42; P = 0.63).
CONCLUSIONS
According to the results, there is no statistically significant difference in different doses of PZQ for treating S. japonicum.
PubMed: 25558390
DOI: 10.5812/ircmj.9600