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Parasite Immunology Jan 2019Previous studies have reported that chemotherapy of schistosomiasis by praziquantel in humans boosts protective antibody responses against S mansoni and S haematobium.... (Meta-Analysis)
Meta-Analysis
AIMS
Previous studies have reported that chemotherapy of schistosomiasis by praziquantel in humans boosts protective antibody responses against S mansoni and S haematobium. A number of studies have reported schistosome-specific antibody levels before and after chemotherapy. Using these reports, a meta-analysis was conducted to identify predictors of population level change in schistosome-specific antibody levels after chemotherapy.
METHODS AND RESULTS
Following a systematic review, 92 observations from 26 articles published between 1988 and 2013 were included in this study. Observations were grouped by antigen type and antibody isotypes for the classification and regression tree (CART) analysis. The study showed that the change in antibody levels was variable: (a) between different human populations and (b) according to the parasite antigen and antibody isotypes. Thus, while anti-worm responses predominantly increased after chemotherapy, anti-egg responses decreased or did not show a significant trend. The change in antibody levels depended on a combination of age and infection intensity for anti-egg IgA, IgM, IgG1, IgG2 and anti-worm IgM and IgG.
CONCLUSION
The study results are consistent with praziquantel treatment boosting anti-worm antibody responses. However, there is considerable heterogeneity in post-treatment changes in specific antibody levels that is related to host age and pre-treatment infection intensity.
Topics: Animals; Anthelmintics; Antibodies, Helminth; Humans; Immunity, Humoral; Praziquantel; Schistosoma haematobium; Schistosoma mansoni; Schistosomiasis; Schistosomiasis haematobia; Schistosomiasis mansoni
PubMed: 30467873
DOI: 10.1111/pim.12604 -
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 -
Host determinants of reinfection with schistosomes in humans: a systematic review and meta-analysis.PLoS Neglected Tropical Diseases Sep 2014Schistosomiasis is still a major public health burden in the tropics and subtropics. Although there is an effective chemotherapy (Praziquantel) for this disease,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Schistosomiasis is still a major public health burden in the tropics and subtropics. Although there is an effective chemotherapy (Praziquantel) for this disease, reinfection occurs rapidly after mass drug administration (MDA). Because the entire population do not get reinfected at the same rate, it is possible that host factors may play a dominant role in determining resistance or susceptibility to reinfection with schistosomes. Here, we systematically reviewed and meta-analyzed studies that reported associations between reinfection with the principal human-infecting species (S. mansoni, S. japonicum and S. haematobium) and host socio-demographic, epidemiological, immunological and genetic factors.
METHODOLOGY/PRINCIPAL FINDINGS
PubMed, Scopus, Google Scholar, Cochrane Review Library and African Journals Online public databases were searched in October 2013 to retrieve studies assessing association of host factors with reinfection with schistosomes. Meta-analysis was performed to generate pooled odds ratios and standardized mean differences as overall effect estimates for dichotomous and continuous variables, respectively. Quality assessment of included studies, heterogeneity between studies and publication bias were also assessed. Out of the initial 2739 records, 109 studies were included in the analyses, of which only 32 studies with 37 data sets were eligible for quantitative data synthesis. Among several host factors identified, strong positive association was found with age and pre-treatment intensity, and only slightly for gender. These factors are major determinants of exposure and disease transmission. Significant positive association was found with anti-SWA IgG4 level, and a negative overall effect for association with IgE levels. This reconfirmed the concept that IgE/IgG4 balance is a major determinant of protective immunity against schistosomiasis. Other identified determinants were reported by a small number of studies to enable interpretation.
CONCLUSIONS
Our data contribute to the understanding of host-parasite interaction as it affects reinfection, and is a potential tool to guide planning and tailoring of community interventions to target high-risk groups.
Topics: Animals; Disease Susceptibility; Host-Parasite Interactions; Humans; Recurrence; Schistosoma; Schistosomiasis
PubMed: 25211227
DOI: 10.1371/journal.pntd.0003164 -
PLoS Neglected Tropical Diseases Jan 2020Preventive chemotherapy is a useful tool for the control of Taenia solium taeniasis and cysticercosis. The aim of this systematic review is to assess the scientific... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preventive chemotherapy is a useful tool for the control of Taenia solium taeniasis and cysticercosis. The aim of this systematic review is to assess the scientific evidence concerning the effectiveness and safety of different drugs in preventive chemotherapy for T. solium taeniasis in endemic populations.
METHODS
A systematic review was conducted of controlled and uncontrolled studies, assessing the efficacy and adverse effects (among other outcomes) of albendazole, niclosamide and/or praziquantel for preventive chemotherapy of T. solium taeniasis. A comprehensive search was conducted for published and unpublished studies. Two reviewers screened articles, completed the data extraction and assessment of risk of bias. A meta-analysis of cure rate and relative reduction in prevalence was performed. The protocol for this review was registered on the International prospective register of systematic reviews (PROSPERO), number CRD42018112533.
RESULTS
We identified 3555 records, of which we included 20 primary studies reported across 33 articles. Meta-analyses of drug and dose showed that a single dose of praziquantel 10mg/kg, albendazole 400mg per day for three consecutive days, or niclosamide 2g, resulted in better cure rates for T. solium taeniasis (99.5%, 96.4% and 84.3%, respectively) than praziquantel 5mg/kg or single dose albendazole 400mg (89.0% and 52.0%, respectively). These findings have a low certainty of evidence due to high risk of bias in individual studies and heterogeneity in combined estimates. In relation to side-effects, most studies reported either no or only mild and transient side-effects within the first three days following drug administration for all drugs and doses.
CONCLUSION
Evidence indicated that praziquantel 10mg/kg, niclosamide 2g, and triple dose albendazole 400mg were effective as taenicides and could be considered for use in mass drug administration programs for the control of T. solium taeniasis. Evidence was not found that any of these drugs caused severe side effects at the indicated doses, although the extent of the available evidence was limited.
Topics: Albendazole; Animals; Anticestodal Agents; Chemoprevention; Cysticercosis; Humans; Niclosamide; Praziquantel; Taenia solium; Taeniasis
PubMed: 31945055
DOI: 10.1371/journal.pntd.0007873 -
Impact of hookworm infection and preventive chemotherapy on haemoglobin in non-pregnant populations.Tropical Medicine & International... Dec 2021To assess the impact of hookworm infection and preventive chemotherapy on haemoglobin levels in non-pregnant populations in endemic areas. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the impact of hookworm infection and preventive chemotherapy on haemoglobin levels in non-pregnant populations in endemic areas.
METHOD
Systematic review and meta-analysis searching PubMed and Web of Science for articles published since 2010 reporting either hookworm prevalence and Hb concentration (cross-sectional studies) or Hb concentration before and after the implementation of preventive chemotherapy (before-after studies and randomised controlled trials [RCTs]). For papers published before 2010, data were extracted from a previously published systematic review. Random effects meta-analyses were conducted to examine the relationship between Hb concentration and hookworm infection intensity (from cross-sectional studies) and the effect of preventive chemotherapy on Hb concentration (from before-after studies and RCTs). Sensitivity analyses investigated the impact of malaria endemicity and combined interventions for schistosomiasis and nutrition status on Hb concentration.
RESULTS
Among cross-sectional studies, both light- and heavy-intensity hookworm infections were associated with lower Hb in school-aged children. School-aged children with heavy hookworm infection in settings of high malaria endemicity had lower mean Hb than those in settings of low malaria endemicity. In non-pregnant populations, deworming with albendazole was associated with an increase in Hb of 3.02 g/L (95% CI 0.1, 6.0 g/L). No additional benefit was seen with deworming using albendazole co-administered with praziquantel for schistosomiasis infection or iron supplementation for nutrition status.
CONCLUSION
Our findings confirm the benefits of preventive chemotherapy as a public health intervention.
Topics: Anemia; Anthelmintics; Controlled Before-After Studies; Cross-Sectional Studies; Hemoglobins; Hookworm Infections; Humans; Randomized Controlled Trials as Topic
PubMed: 34587315
DOI: 10.1111/tmi.13681 -
International Journal of Environmental... Dec 2018We aimed to evaluate the evidence on screening and treatment for two parasitic infections-schistosomiasis and strongyloidiasis-among migrants from endemic countries...
Effectiveness of Screening and Treatment Approaches for Schistosomiasis and Strongyloidiasis in Newly-Arrived Migrants from Endemic Countries in the EU/EEA: A Systematic Review.
We aimed to evaluate the evidence on screening and treatment for two parasitic infections-schistosomiasis and strongyloidiasis-among migrants from endemic countries arriving in the European Union and European Economic Area (EU/EEA). We conducted a systematic search of multiple databases to identify systematic reviews and meta-analyses published between 1 January 1993 and 30 May 2016 presenting evidence on diagnostic and treatment efficacy and cost-effectiveness. We conducted additional systematic search for individual studies published between 2010 and 2017. We assessed the methodological quality of reviews and studies using the AMSTAR, Newcastle⁻Ottawa Scale and QUADAS-II tools. Study synthesis and assessment of the certainty of the evidence was performed using GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. We included 28 systematic reviews and individual studies in this review. The GRADE certainty of evidence was low for the effectiveness of screening techniques and moderate to high for treatment efficacy. Antibody-detecting serological tests are the most effective screening tests for detection of both schistosomiasis and strongyloidiasis in low-endemicity settings, because they have higher sensitivity than conventional parasitological methods. Short courses of praziquantel and ivermectin were safe and highly effective and cost-effective in treating schistosomiasis and strongyloidiasis, respectively. Economic modelling suggests presumptive single-dose treatment of strongyloidiasis with ivermectin for all migrants is likely cost-effective, but feasibility of this strategy has yet to be demonstrated in clinical studies. The evidence supports screening and treatment for schistosomiasis and strongyloidiasis in migrants from endemic countries, to reduce morbidity and mortality.
Topics: Cost-Benefit Analysis; Endemic Diseases; European Union; Humans; Mass Screening; Schistosomiasis; Serologic Tests; Strongyloidiasis; Transients and Migrants
PubMed: 30577567
DOI: 10.3390/ijerph16010011 -
PLoS Neglected Tropical Diseases Oct 2019Schistosomiasis is a widespread public health concern in the poorest regions of the world. The principal control strategy is regular praziquantel administration to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Schistosomiasis is a widespread public health concern in the poorest regions of the world. The principal control strategy is regular praziquantel administration to school-aged children in endemic areas. With calls for the elimination of schistosomiasis as a public health problem, expanding praziquantel delivery to all community members has been advocated. This systematic review and meta-analysis compares the impact of community-wide and child-targeted praziquantel distribution on schistosomiasis prevalence and intensity in school-aged children.
METHODOLOGY/PRINCIPAL FINDINGS
We searched MEDLINE, Embase and Web of Science to identify papers that reported schistosome prevalence before and after praziquantel administration, either to children only or to all community members. Extracted data included Schistosoma species, drug administration strategy, number of treatment rounds, follow-up interval and prevalence and intensity before and after treatment. We used inverse variance weighted generalised linear models to examine the impact of mass versus targeted drug administration on prevalence reduction, and weighted boxplots to examine the impact on infection intensity reduction. This study is registered with PROSPERO, number CRD42018095377. In total, 34 articles were eligible for systematic review and 28 for meta-analysis. Schistosoma mansoni was reported in 20 studies; Schistosoma haematobium in 19 studies, and Schistosoma japonicum in two studies. Results of generalised linear models showed no detectable difference between mass and targeted treatment strategies on prevalence reduction in school-aged children for S. mansoni (odds ratio 0.47, 95%CI 0.13-1.68, p = 0.227) and S. haematobium (0.41, 95%CI 0.06-3.03, p = 0.358). Box plots also showed no apparent differences in intensity reduction between the two treatment strategies.
CONCLUSIONS/SIGNIFICANCE
The results of this meta-analysis do not support the hypothesis that community-wide treatment is more effective than targeted treatment at reducing schistosomiasis infections in children. This may be due to the relatively small number of included studies, insufficient treatment coverage, persistent infection hotspots and unmeasured confounders. Further field-based studies comparing mass and targeted treatment are required.
Topics: Animals; Child; Databases, Factual; Humans; Praziquantel; Prevalence; Schistosoma haematobium; Schistosoma japonicum; Schistosoma mansoni; Schistosomatidae; Schistosomiasis; Schools
PubMed: 31603895
DOI: 10.1371/journal.pntd.0007808 -
BMC Infectious Diseases Jul 2018Cystic echinococcosis (CE) is a well-known neglected parasitic disease. However, evidence supporting the four current treatment modalities is inadequate, and treatment... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cystic echinococcosis (CE) is a well-known neglected parasitic disease. However, evidence supporting the four current treatment modalities is inadequate, and treatment options remain controversial. The aim of this work is to analyse the available data to answer clinical questions regarding medical treatment of CE.
METHODS
A thorough electronic search of the relevant literature without language restrictions was carried out using PubMed (Medline), Cochrane Central Register of Controlled Trials, BioMed, Database of Abstracts of Reviews of Effects, and Cochrane Plus databases up to February 1, 2017. All descriptive studies reporting an assessment of CE treatment and published in a peer-reviewed journal with available full-text were considered for a qualitative analysis. Randomized controlled trials were included in a quantitative meta-analysis. We used the standard methodological procedures established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.
RESULTS
We included 33 studies related to the pharmacological treatment of CE in humans. Of these, 22 studies with levels of evidence 2 to 4 were qualitatively analysed, and 11 randomized controlled trials were quantitatively analysed by meta-analysis.
CONCLUSIONS
Treatment outcomes are better when surgery or PAIR (Puncture, Aspiration, Injection of protoscolicidal agent and Reaspiration) is combined with benzimidazole drugs given pre- and/or post-operation. Albendazole chemotherapy was found to be the primary pharmacological treatment to consider in the medical management of CE. Nevertheless, combined treatment with albendazole plus praziquantel resulted in higher scolicidal and anti-cyst activity and was more likely to result in cure or improvement relative to albendazole alone.
Topics: Albendazole; Anthelmintics; Benzimidazoles; Databases, Factual; Drug Therapy, Combination; Echinococcosis; Humans; Neglected Diseases; Praziquantel; Treatment Outcome
PubMed: 29976137
DOI: 10.1186/s12879-018-3201-y -
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 -
Infectious Diseases of Poverty May 2018Cholangiocarcinoma (CCA) is a fatal bile duct cancer associated with infection by the liver fluke, Opisthorchis viverrini, in the lower Mekong region. Numerous public... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cholangiocarcinoma (CCA) is a fatal bile duct cancer associated with infection by the liver fluke, Opisthorchis viverrini, in the lower Mekong region. Numerous public health interventions have focused on reducing exposure to O. viverrini, but incidence of CCA in the region remains high. While this may indicate the inefficacy of public health interventions due to complex social and cultural factors, it may further indicate other risk factors or interactions with the parasite are important in pathogenesis of CCA. This systematic review aims to provide a comprehensive analysis of described risk factors for CCA in addition to O. viverrini to guide future integrative interventions.
MAIN BODY
We searched five international and seven Thai research databases to identify studies relevant to risk factors for CCA in the lower Mekong region. Selected studies were assessed for risk of bias and quality in terms of study design, population, CCA diagnostic methods, and statistical methods. The final 18 included studies reported numerous risk factors which were grouped into behaviors, socioeconomics, diet, genetics, gender, immune response, other infections, and treatment for O. viverrini. Seventeen risk factors were reported by two or more studies and were assessed with random effects models during meta-analysis. This meta-analysis indicates that the combination of alcohol and smoking (OR = 11.1, 95% CI: 5.63-21.92, P < 0.0001) is most significantly associated with increased risk for CCA and is an even greater risk factor than O. viverrini exposure. This analysis also suggests that family history of cancer, consumption of raw cyprinoid fish, consumption of high nitrate foods, and praziquantel treatment are associated with significantly increased risk. These risk factors may have complex relationships with the host, parasite, or pathogenesis of CCA, and many of these risk factors were found to interact with each other in one or more studies.
CONCLUSIONS
Our findings suggest that a complex variety of risk factors in addition to O. viverrini infection should be addressed in future public health interventions to reduce CCA in affected regions. In particular, smoking and alcohol use, dietary patterns, and socioeconomic factors should be considered when developing intervention programs to reduce CCA.
Topics: Animals; Asia, Southeastern; Cholangiocarcinoma; Incidence; Opisthorchiasis; Opisthorchis; Prevalence; Risk Factors; Thailand
PubMed: 29769113
DOI: 10.1186/s40249-018-0434-3