Proportion of positive results, interquartile range (IQR), minimum-maximum range, and median per diagnostic test at three different time points (baseline) of 24 <i>S. haematobium</i>-positive subjects.

<p>Proportion of positive results, interquartile range (IQR), minimum-maximum range, and median per diagnostic test at three different time points (baseline) of 24 <i>S. haematobium</i>-positive subjects.</p

Spearman's correlation coefficients between values of each diagnostic tool before treatment, and two and 18 months post-treatment (N = 114).

<p>* <i>Note</i>: P-values <0.0001.</p><p>^** Values of real-time PCR are negative as low PCR Ct-values reflect high parasite-specific DNA loads and vice versa.</p

Cumulative percentages and median (IQR) of positive results for each diagnostic test, based on measurement of single urine samples, at three different examination time points of 114 selected <i>Schistosomiasis haematobium</i>-positive schoolchildren.

<p>* <i>Note</i>: missing data cSEA at two months post-treatment (N = 26).</p

Infection prevalence and intensity group as measured by real-time PCR (Ct-values) and microscopy (egg output) at the different examination time points.

<p>Infection prevalence and intensity group as measured by real-time PCR (Ct-values) and microscopy (egg output) at the different examination time points.</p

Evidence That Rhesus Macaques Self-Cure from a <i>Schistosoma japonicum</i> Infection by Disrupting Worm Esophageal Function: A New Route to an Effective Vaccine?

<div><p>Background</p><p>Rhesus macaques are unusual among schistosome hosts, self-curing from an established infection and thereafter manifesting solid immunity against a challenge, an ideal model for vaccine development. Previously, the immunological basis of self-cure was confirmed; surviving worms had ceased feeding but how immunological pressure achieved this was unclear. The schistosome esophagus is not simply a conduit for blood but plays a central role in its processing. Secretions from the anterior and posterior esophageal glands mix with incoming blood causing erythrocyte lysis and tethering and killing of leucocytes.</p><p>Methodology/Principal Findings</p><p>We have analysed the self-cure process in rhesus macaques infected with <i>Schistosoma japonicum</i>. Faecal egg output and circulating antigen levels were used to chart the establishment of a mature worm population and its subsequent demise. The physiological stress of surviving females at perfusion was especially evident from their pale, shrunken appearance, while changes in the structure and function of the esophagus were observed in both sexes. In the anterior region electron microscopy revealed that the vesicle secretory process was disrupted, the tips of lining corrugations being swollen by greatly enlarged vesicles and the putative sites of vesicle release obscured by intense deposits of IgG. The lumen of the posterior esophagus in starving worms was occluded by cellular debris and the lining cytoplasmic plates were closely adherent, also potentially preventing secretion. Seven proteins secreted by the posterior gland were identified and IgG responses were detected to some or all of them. Intrinsic rhesus IgG colocalized with secreted SjMEGs 4.1, 8.2, 9, 11 and VAL-7 on cryosections, suggesting they are potential targets for disruption of function.</p><p>Conclusions/Significance</p><p>Our data suggest that rhesus macaques self-cure by blocking esophagus function with antibody; the protein products of the glands provide a new class of potential vaccine targets.</p></div

Flowchart showing study participation.

<p>Flowchart detailing study participation and adherence of preschool-aged children for submitting two stool and two urine samples for the diagnosis of <i>S. mansoni</i>, <i>S. haematobium</i>, and soil-transmitted helminths before and after administration of praziquantel in the two study villages in the Azaguié district, south Côte d'Ivoire, in August and September 2011.</p

Agreement between Kato-Katz technique and POC-CCA cassette test for the diagnosis of <i>S. mansoni</i>.

<p>The study was carried out in Azaguié, south Côte d'Ivoire in August and September 2011.</p>*<p>κ indicating kappa; κ<0, no agreement; κ = 0–0.2, poor agreement; κ = 0.21–0.4, fair agreement; κ = 0.41–0.6, moderate agreement; κ = 0.61–0.8, substantial agreement; κ = 0.81–1.0, almost perfect agreement <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002109#pntd.0002109-Landis1" target="_blank">[35]</a>.</p><p>t−, trace negative; t+, trace positive.</p

Host antibody binds to the posterior esophagus which shows an altered cellular morphology.

<p>(A) TEM image of the posterior esophagus, showing the luminal plates (P) tightly packed and closely adherent. The lumen appears congested, occluded by debris and host cells (HC) in the center; electron dense structures (arrowed) are also visible around the edges of the debris. (B) SEM image of the plates in the posterior esophagus, showing that intervening spaces are largely absent. (C) TEM image at high magnification reveals the parallel tramline appearance of posterior esophageal plates. Where two adjacent plates are particularly closely adherent, membranous material is visible (MM, arrowed) bound to the luminal surface. The two lighter lines in the center of each plate denote the basal invagination (BI). (D) High magnification image of electron dense structures revealing they are aggregates of membranous material. Confocal images of male worm heads: (E) a longitudinal section, stained with AF488 labeled anti-monkey IgG, and (F) a transverse section, stained with Cy3 labelled anti-monkey IgG. (E) is counterstained with DAPI (blue) and phalloidin (orange) to highlight the nuclei and musculature and (F) with DAPI only. Both images reveal that intrinsic antibody (green in E, red in F) has bound to the post esophageal lining (PEL). The luminal edges of lining plates are strongly positive whilst the surface of the plates is more weakly stained. Scale bars: 20 μm (A, E, F), 2 μm (B), 200 nm (C, D).</p

Antibody targets the worm esophagus and shows distinct response patterns to worm and egg antigens.

<p>Permeabilized whole worms recovered from rhesus macaques, (A) female and (B) male, reacted with FITC-labeled anti-rhesus IgG, showed intrinsic antibodies (green) bound to the tegument, particularly in the head region, but more strikingly along the whole length of the esophageal lumen (arrowed). (C) Time course of antibody response against soluble worm antigen (SWAP), and egg antigen (SEA) preparations. Binding of antibody to both preparations was barely detected during the first 4 weeks. Thereafter the anti-SEA response rose dramatically to reach a high plateau at week 8, but the decline from week 10 onwards was not significant. In contrast, anti-SWAP reactivity rose only slowly from week 4, with its peak appearing as late as week 18. Scale bars: 50 μm (A), 20 μm (B).</p

Number of preschool-aged children falling in each POC-CCA test score before and after treatment.

<p><i>n</i> = 86, Day 1: first day of urine collection, Day 2: second day of urine collection.</p>a<p>Combined POC-CCA cassette test (days 1 and 2), as defined in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002109#pntd-0002109-t001" target="_blank">Table 1</a>.</p>b<p>The higher POC-CCA cassette test score from either day 1 or day 2 was considered as final score.</p