Meta-analysis of five studies assessing miltefosine compared to meglumine antimoniate in clinical failure at 6 months of follow up.

<p>Meta-analysis of five studies assessing miltefosine compared to meglumine antimoniate in clinical failure at 6 months of follow up.</p

Interventions for American Cutaneous and Mucocutaneous Leishmaniasis: A Systematic Review Update

<div><p>Introduction</p><p>Leishmaniasis is an important public health problem in the Americas. A Cochrane review published in 2009 analyzed 38 randomized controlled trials (RCT). We conducted a systematic review to evaluate the effects of therapeutic interventions for American cutaneous and mucocutaneous leishmaniasis.</p><p>Methods</p><p>All studies were extracted from PubMed, Embase, Lilacs (2009 to July, 2012 respectively), the Cochrane Central Register of Controlled Trials (6-2012) and references of identified publications. RCTs’ risk of bias was assessed.</p><p>Results</p><p>We identified 1865 references of interest; we finally included 10 new RCTs. The risk of bias scored low or unclear for most domains. Miltefosine was not significantly different from meglumine antimoniate in the complete cure rate at 6 months (4 RCT; 584 participants; ITT; RR: 1.12; 95%CI: 0.85 to 1.47; I2 78%). However a significant difference in the rate of complete cure favoring miltefosine at 6 months was found in L. panamensis and L. guyanensis (2 RCTs, 206 participants; ITT; RR: 1.22; 95%CI: 1.02 to 1.46; I2 0%). One RCT found that meglumine antimoniate was superior to pentamidine in the rate of complete cure for L. braziliensis (80 participants, ITT; RR: 2.21; 95%CI: 1.41 to 3.49), while another RCT assessing L. guyanensis did not find any significant difference. Although meta-analysis of three studies found a significant difference in the rate of complete cure at 3 months favoring imiquimod versus placebo (134 participants; ITT; RR: 1.45; 95%CI: 1.12 to 1.88; I2 0%), no significant differences were found at 6 and 12 months. Thermotherapy and nitric oxide were not superior to meglumine antimoniate.</p><p>Conclusion</p><p>Therapeutic interventions for American cutaneous and mucocutaneous leishmaniasis are varied and should be decided according to the context. Since mucosal disease is the more neglected form of leishmaniasis a multicentric trial should be urgently considered.</p></div

Main finding from Cochrane review and this update for complete cure.

*<p>Significant difference favoring this intervention.</p

Meta-analysis of four RCTs assessing miltefosine compared to meglumine antimoniate in the complete cure rate at 6 months of follow up.

<p>Meta-analysis of four RCTs assessing miltefosine compared to meglumine antimoniate in the complete cure rate at 6 months of follow up.</p

Frequency and severity of histological lesions in guinea pig dams and their fetuses in response to infection by <i>Trypanosoma cruzi</i>.

<p>Frequency and severity of histological lesions in guinea pig dams and their fetuses in response to infection by <i>Trypanosoma cruzi</i>.</p

Serological and parasitological analysis of fetuses of guinea pigs infected with <i>T</i>. <i>cruzi</i>.

<p>Female guinea pigs were infected before gestation (IBG) or during gestation (IDG). <b>(A&B)</b> Sera samples of fetuses were obtained close to parturition, and analyzed by an ELISA <b><i>(A)</i></b> and indirect immunofluorescence assay <b>(B)</b>. Bar graphs show the percentage of fetuses in each group that were positive for anti-<i>T</i>. <i>cruzi</i> antibodies. <b>(C)</b> Fetal tissue parasite load was monitored by quantitative PCR as described in Materials and Methods. Control (n = 9); IBG (n = 9); IDG (n = 5) samples were analyzed in triplicate. Data in panel A & B are presented as absolute values, and data in panel C are presented as mean value ± SD. (**P <0.01, IDG vs. IBG).</p

Serological and parasitological analysis of guinea pig dams infected with <i>T</i>. <i>cruzi</i>.

<p><b>(A)</b> Chronogram of female guinea pigs infected before gestation (IBG) and infected during gestation (IDG). The time-points (days) of breeding (⚤), <i>T</i>. <i>cruzi</i> (<i>Tc</i>) inoculation (black arrow), and euthanasia (marked by X) are shown. Females that were mated but not infected were used as controls. <b>(B&C)</b> An ELISA <b>(B)</b> and Western blotting <b>(C)</b> were performed to monitor the anti-T. <i>cruzi</i> antibodies in sera samples of control, IBG and IDG dams at parturition. Bar graphs show the percentage of dams that were positive for anti-<i>T</i>. <i>cruzi</i> antibodies. <b>(D&E)</b> Quantitative PCR evaluation of blood <b>(D)</b> and heart tissue <b>(E)</b> parasite load in control, IBG and IDG dams is shown. * P<0.05.</p

Histological evaluation of the heart of dams.

<p>Guinea pigs were infected with <i>T</i>. <i>cruzi</i> before (IBG) or during (IDG) gestation, and harvested close to parturition, as described in Materials and Methods and <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006222#pntd.0006222.g001" target="_blank">Fig 1A</a>. Shown are the representative images of the H&E staining of the heart tissue sections from <b>(A)</b> Control, <b>(B)</b> IBG, and <b>(C)</b> IDG dams. Semi-quantitative score of inflammatory infiltrate is presented in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006222#pntd.0006222.t001" target="_blank">Table 1</a>.</p

Effect of T. <i>cruzi</i> infection on fetal growth.

<p>Female guinea pigs were infected before gestation (IBG) or during gestation (IDG) as shown in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006222#pntd.0006222.g001" target="_blank">Fig 1A</a>. Guinea pigs that were mated but not infected were used as controls. Fetal characteristics, including number of fetuses carried per guinea pig <b>(A)</b>, fetal weight <b>(B)</b>, fetal abdominal width <b>(C)</b> and fetal crown-rump length <b>(D)</b> were monitored close to parturition. Data are presented as mean value ± SD, and significance (* P < 0.05, control vs. infected) is plotted.</p

TPP for point-of-care diagnosis for patients in the acute phase of Chagas disease.

<p>TPP for point-of-care diagnosis for patients in the acute phase of Chagas disease.</p