Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection
Background Prevention of chronic chagasic cardiomyopathy (CCC) by treating infected populations with trypanocidal therapy (TT) remains a challenge. Despite a renewed enthusiasm for TT, uncertainty regarding its efficacy, concerns about its safety and limited availability remain barriers for a wider...
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| Veröffentlicht in: | Cochrane database of systematic reviews 2014-05, Vol.2014 (5), p.CD003463-CD003463 |
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| creator | Villar, Juan Carlos Perez, Juan Guillermo Cortes, Olga Lucia Riarte, Adelina Pepper, Micah Marin‐Neto, Jose Antonio Guyatt, Gordon H Villar, Juan Carlos |
| description | Background
Prevention of chronic chagasic cardiomyopathy (CCC) by treating infected populations with trypanocidal therapy (TT) remains a challenge. Despite a renewed enthusiasm for TT, uncertainty regarding its efficacy, concerns about its safety and limited availability remain barriers for a wider use of conventional drugs. We have updated a previous version of this review.
Objectives
To systematically search, appraise, identify and extract data from eligible studies comparing the outcome of cohorts of seropositive individuals to Trypanosoma cruzi exposed to TT versus placebo or no treatment.
Search methods
We sought eligible studies in electronic databases (Cochrane Central Register of Controlled Trials (CENTRAL), Issue 1, 2014); MEDLINE (Ovid, 1946 to January week 5 2014); EMBASE (Ovid, 1980 to 2014 week 6) and LILACS (up to 6 May 2010)) by combining terms related with the disease and the treatment. The search also included a Google search, handsearch for references in review or selected articles, and search of expert files. We applied no language restrictions.
Selection criteria
Review authors screened the retrieved references for eligibility (those dealing with human participants treated with TT) and then assessed the pre‐selected studies in full for inclusion. We included randomised controlled trials (RCTs) and observational studies that provided data on either mortality or clinical progression of CCC after at least four years of follow‐up.
Data collection and analysis
Teams of two review authors independently carried out the study selection, data extraction and risk of bias assessment, with a referee resolving disagreement within the pairs. Data collection included study design, characteristics of the population and interventions or exposures and outcome measures. We defined categories of outcome data as parasite‐related (positive serology, xenodiagnosis or polymerase chain reaction (PCR) after TT) and participant‐related (including efficacy outcomes such as progression towards CCC, all‐cause mortality and side effects of TT). We reported pooled outcome data as Mantel‐Haenszel odds ratios (OR) or standardised mean differences (SMD) along with 95% confidence intervals (CI), using a random‐effects model. I2 statistics provided an estimate of heterogeneity across studies. We conducted an exploratory meta‐regression analysis of the relationship between positive‐serology and progression of CCC or mortality.
Main results
We included 13 studies involving 4 |
| doi_str_mv | 10.1002/14651858.CD003463.pub2 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7154579</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1531952204</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4992-b21e102254b074d8e8c6d5a4f8eff166f6a0edad02c56e14840cbd840667c0fa3</originalsourceid><addsrcrecordid>eNqFUV1PwyAUJUbj5vQvLH30pRMo0PbFRKdOkyW-zGdCKWyYtlRoNfPXy7KPTF98AW7Ouedc7gFgjOAEQYhvEGEUZTSbTB8gTAhLJm1f4BMw3ADxBjk9eg_AhffvgchynJ6DASYZS7OUDcFs4dataKw0paii0vVLH2nrIrlytjEyEn5dt52tRReKHdeHMpKu_zaRabSSnbHNJTjTovLqanePwNvT42L6HM9fZy_Tu3ksSZ7juMBIIYgxJQVMSZmpTLKSCqIzpTViTDMBVSlKiCVlCpGMQFmU4WQslVCLZARut7rhu7UqpWo6JyreOlMLt-ZWGP4bacyKL-0nTxElNM2DwPVOwNmPXvmO18ZLVVWiUbb3HNEE5RRjSAKVbanSWe-d0gcbBPkmBb5Pge9T2Jjj0Dg-HvLQtl97INxvCV-mUmsubVh38P9H94_LD5Pkmi4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1531952204</pqid></control><display><type>article</type><title>Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><source>Cochrane Library</source><creator>Villar, Juan Carlos ; Perez, Juan Guillermo ; Cortes, Olga Lucia ; Riarte, Adelina ; Pepper, Micah ; Marin‐Neto, Jose Antonio ; Guyatt, Gordon H ; Villar, Juan Carlos</creator><creatorcontrib>Villar, Juan Carlos ; Perez, Juan Guillermo ; Cortes, Olga Lucia ; Riarte, Adelina ; Pepper, Micah ; Marin‐Neto, Jose Antonio ; Guyatt, Gordon H ; Villar, Juan Carlos</creatorcontrib><description>Background
Prevention of chronic chagasic cardiomyopathy (CCC) by treating infected populations with trypanocidal therapy (TT) remains a challenge. Despite a renewed enthusiasm for TT, uncertainty regarding its efficacy, concerns about its safety and limited availability remain barriers for a wider use of conventional drugs. We have updated a previous version of this review.
Objectives
To systematically search, appraise, identify and extract data from eligible studies comparing the outcome of cohorts of seropositive individuals to Trypanosoma cruzi exposed to TT versus placebo or no treatment.
Search methods
We sought eligible studies in electronic databases (Cochrane Central Register of Controlled Trials (CENTRAL), Issue 1, 2014); MEDLINE (Ovid, 1946 to January week 5 2014); EMBASE (Ovid, 1980 to 2014 week 6) and LILACS (up to 6 May 2010)) by combining terms related with the disease and the treatment. The search also included a Google search, handsearch for references in review or selected articles, and search of expert files. We applied no language restrictions.
Selection criteria
Review authors screened the retrieved references for eligibility (those dealing with human participants treated with TT) and then assessed the pre‐selected studies in full for inclusion. We included randomised controlled trials (RCTs) and observational studies that provided data on either mortality or clinical progression of CCC after at least four years of follow‐up.
Data collection and analysis
Teams of two review authors independently carried out the study selection, data extraction and risk of bias assessment, with a referee resolving disagreement within the pairs. Data collection included study design, characteristics of the population and interventions or exposures and outcome measures. We defined categories of outcome data as parasite‐related (positive serology, xenodiagnosis or polymerase chain reaction (PCR) after TT) and participant‐related (including efficacy outcomes such as progression towards CCC, all‐cause mortality and side effects of TT). We reported pooled outcome data as Mantel‐Haenszel odds ratios (OR) or standardised mean differences (SMD) along with 95% confidence intervals (CI), using a random‐effects model. I2 statistics provided an estimate of heterogeneity across studies. We conducted an exploratory meta‐regression analysis of the relationship between positive‐serology and progression of CCC or mortality.
Main results
We included 13 studies involving 4229 participants (six RCTs, n = 1096, five RCTs of intermediate risk of bias, one RCT of high risk of bias; four non‐randomised experiments, n = 1639 and three observational studies, n = 1494). Ten studies tested nitroderivative drugs nifurtimox or benznidazole (three exposed participants to allopurinol, one to itraconazole). Five studies were conducted in Brazil, five in Argentina, one in Bolivia, one in Chile and one in Venezuela.
TT was associated with substantial, but heterogeneous reductions on parasite‐related outcomes such as positive serology (9 studies, OR 0.21, 95% CI 0.10 to 0.44, I2 = 76%), positive PCR (2 studies, OR 0.50, 95% CI 0.27 to 0.92, I2 = 0%), positive xenodiagnosis after treatment (6 studies, OR 0.35, 95% CI 0.14 to 0.86, I2 = 79%), or reduction on antibody titres (3 studies, SMD ‐0.56, 95% CI ‐0.89 to ‐0.23, I2 = 28%). Efficacy data on patient‐related outcomes was largely from non‐RCTs. TT with nitroderivatives was associated with potentially important, but imprecise and inconsistent reductions in progression of CCC (4 studies, 106 events, OR 0.74, 95% CI 0.32 to 1.73, I2 = 66%) and mortality after TT (6 studies, 99 events, OR 0.55, 95% CI 0.26 to 1.14, I2 = 48%). The overall median incidence of any severe side effects among 1475 individuals from five studies exposed to TT was 2.7%, and the overall discontinuation of this two‐month therapy in RCTs (5 studies, 134 events) was 20.5% (versus 4.3% among controls) and 10.4% in other five studies (125 events).
Authors' conclusions
Despite the evidence that TT reduced parasite‐related outcomes, the low quality and inconsistency of the data for patient‐important outcomes must be treated with caution. More geographically diverse RCTs testing newer forms of TT are warranted in order to 1. estimate efficacy more precisely, 2. explore factors potentially responsible for the heterogeneity of results and 3. increase knowledge on the efficacy/tolerance balance of conventional TT.</description><identifier>ISSN: 1465-1858</identifier><identifier>EISSN: 1465-1858</identifier><identifier>EISSN: 1469-493X</identifier><identifier>DOI: 10.1002/14651858.CD003463.pub2</identifier><identifier>PMID: 24867876</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Animals ; Cardiomyopathy ; Chagas Cardiomyopathy ; Chagas Cardiomyopathy - prevention & control ; Chagas Disease ; Chagas disease (American trypanosomiasis) ; Chagas Disease - drug therapy ; Child health ; Chronic Disease ; H. Chagas Cardiomyopathy ; H.1 Drugs ; Heart & circulation ; Humans ; Infectious disease ; Medicine General & Introductory Medical Sciences ; Neglected tropical diseases ; Observational Studies as Topic ; Randomized Controlled Trials as Topic ; Trypanocidal Agents ; Trypanocidal Agents - therapeutic use ; Trypanosoma cruzi</subject><ispartof>Cochrane database of systematic reviews, 2014-05, Vol.2014 (5), p.CD003463-CD003463</ispartof><rights>Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4992-b21e102254b074d8e8c6d5a4f8eff166f6a0edad02c56e14840cbd840667c0fa3</citedby><cites>FETCH-LOGICAL-c4992-b21e102254b074d8e8c6d5a4f8eff166f6a0edad02c56e14840cbd840667c0fa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24867876$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Villar, Juan Carlos</creatorcontrib><creatorcontrib>Perez, Juan Guillermo</creatorcontrib><creatorcontrib>Cortes, Olga Lucia</creatorcontrib><creatorcontrib>Riarte, Adelina</creatorcontrib><creatorcontrib>Pepper, Micah</creatorcontrib><creatorcontrib>Marin‐Neto, Jose Antonio</creatorcontrib><creatorcontrib>Guyatt, Gordon H</creatorcontrib><creatorcontrib>Villar, Juan Carlos</creatorcontrib><title>Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection</title><title>Cochrane database of systematic reviews</title><addtitle>Cochrane Database Syst Rev</addtitle><description>Background
Prevention of chronic chagasic cardiomyopathy (CCC) by treating infected populations with trypanocidal therapy (TT) remains a challenge. Despite a renewed enthusiasm for TT, uncertainty regarding its efficacy, concerns about its safety and limited availability remain barriers for a wider use of conventional drugs. We have updated a previous version of this review.
Objectives
To systematically search, appraise, identify and extract data from eligible studies comparing the outcome of cohorts of seropositive individuals to Trypanosoma cruzi exposed to TT versus placebo or no treatment.
Search methods
We sought eligible studies in electronic databases (Cochrane Central Register of Controlled Trials (CENTRAL), Issue 1, 2014); MEDLINE (Ovid, 1946 to January week 5 2014); EMBASE (Ovid, 1980 to 2014 week 6) and LILACS (up to 6 May 2010)) by combining terms related with the disease and the treatment. The search also included a Google search, handsearch for references in review or selected articles, and search of expert files. We applied no language restrictions.
Selection criteria
Review authors screened the retrieved references for eligibility (those dealing with human participants treated with TT) and then assessed the pre‐selected studies in full for inclusion. We included randomised controlled trials (RCTs) and observational studies that provided data on either mortality or clinical progression of CCC after at least four years of follow‐up.
Data collection and analysis
Teams of two review authors independently carried out the study selection, data extraction and risk of bias assessment, with a referee resolving disagreement within the pairs. Data collection included study design, characteristics of the population and interventions or exposures and outcome measures. We defined categories of outcome data as parasite‐related (positive serology, xenodiagnosis or polymerase chain reaction (PCR) after TT) and participant‐related (including efficacy outcomes such as progression towards CCC, all‐cause mortality and side effects of TT). We reported pooled outcome data as Mantel‐Haenszel odds ratios (OR) or standardised mean differences (SMD) along with 95% confidence intervals (CI), using a random‐effects model. I2 statistics provided an estimate of heterogeneity across studies. We conducted an exploratory meta‐regression analysis of the relationship between positive‐serology and progression of CCC or mortality.
Main results
We included 13 studies involving 4229 participants (six RCTs, n = 1096, five RCTs of intermediate risk of bias, one RCT of high risk of bias; four non‐randomised experiments, n = 1639 and three observational studies, n = 1494). Ten studies tested nitroderivative drugs nifurtimox or benznidazole (three exposed participants to allopurinol, one to itraconazole). Five studies were conducted in Brazil, five in Argentina, one in Bolivia, one in Chile and one in Venezuela.
TT was associated with substantial, but heterogeneous reductions on parasite‐related outcomes such as positive serology (9 studies, OR 0.21, 95% CI 0.10 to 0.44, I2 = 76%), positive PCR (2 studies, OR 0.50, 95% CI 0.27 to 0.92, I2 = 0%), positive xenodiagnosis after treatment (6 studies, OR 0.35, 95% CI 0.14 to 0.86, I2 = 79%), or reduction on antibody titres (3 studies, SMD ‐0.56, 95% CI ‐0.89 to ‐0.23, I2 = 28%). Efficacy data on patient‐related outcomes was largely from non‐RCTs. TT with nitroderivatives was associated with potentially important, but imprecise and inconsistent reductions in progression of CCC (4 studies, 106 events, OR 0.74, 95% CI 0.32 to 1.73, I2 = 66%) and mortality after TT (6 studies, 99 events, OR 0.55, 95% CI 0.26 to 1.14, I2 = 48%). The overall median incidence of any severe side effects among 1475 individuals from five studies exposed to TT was 2.7%, and the overall discontinuation of this two‐month therapy in RCTs (5 studies, 134 events) was 20.5% (versus 4.3% among controls) and 10.4% in other five studies (125 events).
Authors' conclusions
Despite the evidence that TT reduced parasite‐related outcomes, the low quality and inconsistency of the data for patient‐important outcomes must be treated with caution. More geographically diverse RCTs testing newer forms of TT are warranted in order to 1. estimate efficacy more precisely, 2. explore factors potentially responsible for the heterogeneity of results and 3. increase knowledge on the efficacy/tolerance balance of conventional TT.</description><subject>Animals</subject><subject>Cardiomyopathy</subject><subject>Chagas Cardiomyopathy</subject><subject>Chagas Cardiomyopathy - prevention & control</subject><subject>Chagas Disease</subject><subject>Chagas disease (American trypanosomiasis)</subject><subject>Chagas Disease - drug therapy</subject><subject>Child health</subject><subject>Chronic Disease</subject><subject>H. Chagas Cardiomyopathy</subject><subject>H.1 Drugs</subject><subject>Heart & circulation</subject><subject>Humans</subject><subject>Infectious disease</subject><subject>Medicine General & Introductory Medical Sciences</subject><subject>Neglected tropical diseases</subject><subject>Observational Studies as Topic</subject><subject>Randomized Controlled Trials as Topic</subject><subject>Trypanocidal Agents</subject><subject>Trypanocidal Agents - therapeutic use</subject><subject>Trypanosoma cruzi</subject><issn>1465-1858</issn><issn>1465-1858</issn><issn>1469-493X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>RWY</sourceid><sourceid>EIF</sourceid><recordid>eNqFUV1PwyAUJUbj5vQvLH30pRMo0PbFRKdOkyW-zGdCKWyYtlRoNfPXy7KPTF98AW7Ouedc7gFgjOAEQYhvEGEUZTSbTB8gTAhLJm1f4BMw3ADxBjk9eg_AhffvgchynJ6DASYZS7OUDcFs4dataKw0paii0vVLH2nrIrlytjEyEn5dt52tRReKHdeHMpKu_zaRabSSnbHNJTjTovLqanePwNvT42L6HM9fZy_Tu3ksSZ7juMBIIYgxJQVMSZmpTLKSCqIzpTViTDMBVSlKiCVlCpGMQFmU4WQslVCLZARut7rhu7UqpWo6JyreOlMLt-ZWGP4bacyKL-0nTxElNM2DwPVOwNmPXvmO18ZLVVWiUbb3HNEE5RRjSAKVbanSWe-d0gcbBPkmBb5Pge9T2Jjj0Dg-HvLQtl97INxvCV-mUmsubVh38P9H94_LD5Pkmi4</recordid><startdate>20140527</startdate><enddate>20140527</enddate><creator>Villar, Juan Carlos</creator><creator>Perez, Juan Guillermo</creator><creator>Cortes, Olga Lucia</creator><creator>Riarte, Adelina</creator><creator>Pepper, Micah</creator><creator>Marin‐Neto, Jose Antonio</creator><creator>Guyatt, Gordon H</creator><creator>Villar, Juan Carlos</creator><general>John Wiley & Sons, Ltd</general><scope>7PX</scope><scope>RWY</scope><scope>ZYTZH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20140527</creationdate><title>Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection</title><author>Villar, Juan Carlos ; Perez, Juan Guillermo ; Cortes, Olga Lucia ; Riarte, Adelina ; Pepper, Micah ; Marin‐Neto, Jose Antonio ; Guyatt, Gordon H ; Villar, Juan Carlos</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4992-b21e102254b074d8e8c6d5a4f8eff166f6a0edad02c56e14840cbd840667c0fa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Cardiomyopathy</topic><topic>Chagas Cardiomyopathy</topic><topic>Chagas Cardiomyopathy - prevention & control</topic><topic>Chagas Disease</topic><topic>Chagas disease (American trypanosomiasis)</topic><topic>Chagas Disease - drug therapy</topic><topic>Child health</topic><topic>Chronic Disease</topic><topic>H. Chagas Cardiomyopathy</topic><topic>H.1 Drugs</topic><topic>Heart & circulation</topic><topic>Humans</topic><topic>Infectious disease</topic><topic>Medicine General & Introductory Medical Sciences</topic><topic>Neglected tropical diseases</topic><topic>Observational Studies as Topic</topic><topic>Randomized Controlled Trials as Topic</topic><topic>Trypanocidal Agents</topic><topic>Trypanocidal Agents - therapeutic use</topic><topic>Trypanosoma cruzi</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Villar, Juan Carlos</creatorcontrib><creatorcontrib>Perez, Juan Guillermo</creatorcontrib><creatorcontrib>Cortes, Olga Lucia</creatorcontrib><creatorcontrib>Riarte, Adelina</creatorcontrib><creatorcontrib>Pepper, Micah</creatorcontrib><creatorcontrib>Marin‐Neto, Jose Antonio</creatorcontrib><creatorcontrib>Guyatt, Gordon H</creatorcontrib><creatorcontrib>Villar, Juan Carlos</creatorcontrib><collection>Wiley-Blackwell Cochrane Library</collection><collection>Cochrane Library</collection><collection>Cochrane Library (Open Aceess)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cochrane database of systematic reviews</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Villar, Juan Carlos</au><au>Perez, Juan Guillermo</au><au>Cortes, Olga Lucia</au><au>Riarte, Adelina</au><au>Pepper, Micah</au><au>Marin‐Neto, Jose Antonio</au><au>Guyatt, Gordon H</au><au>Villar, Juan Carlos</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection</atitle><jtitle>Cochrane database of systematic reviews</jtitle><addtitle>Cochrane Database Syst Rev</addtitle><date>2014-05-27</date><risdate>2014</risdate><volume>2014</volume><issue>5</issue><spage>CD003463</spage><epage>CD003463</epage><pages>CD003463-CD003463</pages><issn>1465-1858</issn><eissn>1465-1858</eissn><eissn>1469-493X</eissn><abstract>Background
Prevention of chronic chagasic cardiomyopathy (CCC) by treating infected populations with trypanocidal therapy (TT) remains a challenge. Despite a renewed enthusiasm for TT, uncertainty regarding its efficacy, concerns about its safety and limited availability remain barriers for a wider use of conventional drugs. We have updated a previous version of this review.
Objectives
To systematically search, appraise, identify and extract data from eligible studies comparing the outcome of cohorts of seropositive individuals to Trypanosoma cruzi exposed to TT versus placebo or no treatment.
Search methods
We sought eligible studies in electronic databases (Cochrane Central Register of Controlled Trials (CENTRAL), Issue 1, 2014); MEDLINE (Ovid, 1946 to January week 5 2014); EMBASE (Ovid, 1980 to 2014 week 6) and LILACS (up to 6 May 2010)) by combining terms related with the disease and the treatment. The search also included a Google search, handsearch for references in review or selected articles, and search of expert files. We applied no language restrictions.
Selection criteria
Review authors screened the retrieved references for eligibility (those dealing with human participants treated with TT) and then assessed the pre‐selected studies in full for inclusion. We included randomised controlled trials (RCTs) and observational studies that provided data on either mortality or clinical progression of CCC after at least four years of follow‐up.
Data collection and analysis
Teams of two review authors independently carried out the study selection, data extraction and risk of bias assessment, with a referee resolving disagreement within the pairs. Data collection included study design, characteristics of the population and interventions or exposures and outcome measures. We defined categories of outcome data as parasite‐related (positive serology, xenodiagnosis or polymerase chain reaction (PCR) after TT) and participant‐related (including efficacy outcomes such as progression towards CCC, all‐cause mortality and side effects of TT). We reported pooled outcome data as Mantel‐Haenszel odds ratios (OR) or standardised mean differences (SMD) along with 95% confidence intervals (CI), using a random‐effects model. I2 statistics provided an estimate of heterogeneity across studies. We conducted an exploratory meta‐regression analysis of the relationship between positive‐serology and progression of CCC or mortality.
Main results
We included 13 studies involving 4229 participants (six RCTs, n = 1096, five RCTs of intermediate risk of bias, one RCT of high risk of bias; four non‐randomised experiments, n = 1639 and three observational studies, n = 1494). Ten studies tested nitroderivative drugs nifurtimox or benznidazole (three exposed participants to allopurinol, one to itraconazole). Five studies were conducted in Brazil, five in Argentina, one in Bolivia, one in Chile and one in Venezuela.
TT was associated with substantial, but heterogeneous reductions on parasite‐related outcomes such as positive serology (9 studies, OR 0.21, 95% CI 0.10 to 0.44, I2 = 76%), positive PCR (2 studies, OR 0.50, 95% CI 0.27 to 0.92, I2 = 0%), positive xenodiagnosis after treatment (6 studies, OR 0.35, 95% CI 0.14 to 0.86, I2 = 79%), or reduction on antibody titres (3 studies, SMD ‐0.56, 95% CI ‐0.89 to ‐0.23, I2 = 28%). Efficacy data on patient‐related outcomes was largely from non‐RCTs. TT with nitroderivatives was associated with potentially important, but imprecise and inconsistent reductions in progression of CCC (4 studies, 106 events, OR 0.74, 95% CI 0.32 to 1.73, I2 = 66%) and mortality after TT (6 studies, 99 events, OR 0.55, 95% CI 0.26 to 1.14, I2 = 48%). The overall median incidence of any severe side effects among 1475 individuals from five studies exposed to TT was 2.7%, and the overall discontinuation of this two‐month therapy in RCTs (5 studies, 134 events) was 20.5% (versus 4.3% among controls) and 10.4% in other five studies (125 events).
Authors' conclusions
Despite the evidence that TT reduced parasite‐related outcomes, the low quality and inconsistency of the data for patient‐important outcomes must be treated with caution. More geographically diverse RCTs testing newer forms of TT are warranted in order to 1. estimate efficacy more precisely, 2. explore factors potentially responsible for the heterogeneity of results and 3. increase knowledge on the efficacy/tolerance balance of conventional TT.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>24867876</pmid><doi>10.1002/14651858.CD003463.pub2</doi><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Cochrane Library |
| subjects | Animals Cardiomyopathy Chagas Cardiomyopathy Chagas Cardiomyopathy - prevention & control Chagas Disease Chagas disease (American trypanosomiasis) Chagas Disease - drug therapy Child health Chronic Disease H. Chagas Cardiomyopathy H.1 Drugs Heart & circulation Humans Infectious disease Medicine General & Introductory Medical Sciences Neglected tropical diseases Observational Studies as Topic Randomized Controlled Trials as Topic Trypanocidal Agents Trypanocidal Agents - therapeutic use Trypanosoma cruzi |
| title | Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection |
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