Rapidly boosted Plasma IL-5 induced by treatment of human <em>Schistosomiasis haematobium</em> is dependent on antigen dose, IgE and eosinophils

IgE specific to worm antigen (SWA) and pre-treatment eosinophil number, are associated with human immunity to re-infection with schistosomes after chemotherapeutic treatment. Treatment significantly elevates circulating IL-5 24-hr post-treatment of Schistosoma mansoni. Here we investigate if praziquantel treatment of human schistosomiasis haematobium also boosts circulating IL-5, the immunological and parasitological factors that predispose to this, and the relationship between these and subsequent immunity to post-treatment re-infection.The relationship between pre-treatment SWA-IgE, eosinophil number and infection intensity and the 24-hr post-treatment IL-5 boost was investigated in a Malian cohort (aged 5-40 yrs), exposed to S. haematobium. Eotaxin levels were measured at 24-hr post-treatment as a proxy of eosinophil migration. The relationship between the 24-hr post-treatment IL-5 boost and later eosinophil numbers and SWA-IgE levels (9-wk post-treatment) was examined, then investigated in the context of subsequent levels of re-infection (2-yr post-treatment). Circulating IL-5 levels increased 24-hr post-treatment and were associated with pre-treatment infection intensity, SWA-IgE levels, eosinophil number, as well as 24-hr post-treatment eotaxin levels. 24-hr IL-5 levels were, in turn, significantly associated with eosinophil number and elevated SWA-IgE 9-wk later. These SWA-IgE levels were significantly associated with immunity to re-infection.Early IL-5 production after treatment-induced exposure to S. haematobium worm antigen is positively associated with antigen dose (infection intensity), IgE availability for arming of effector cells at time of treatment and subsequent eosinophil migration response (as indicated by eotaxin levels). The IL-5 produced is positively associated with increased downstream eosinophil number and increases in specific IgE levels, implicating this cytokine boost and its down-stream consequences in the production and maintenance of IgE, and subsequent re-infection immunity

Linear regression models of boost in SWA-IgE at 9 weeks post-treatment.

*<p>p<0.05,</p>**<p>p<0.01.</p

Linear regression model of the boost in levels of plasma IL-5.

*<p>p<0.05,</p>***<p>p<0.001.</p

Linear regression models of the boost in eosinophil number at 9 weeks post-treatment.

*<p>p<0.05,</p>**<p>p<0.01,</p>***<p>p<0.001.</p

Logistic regression models of re-infection status.

*<p>p<0.05,</p>**<p>p<0.01,</p>***<p>p<0.001.</p

Baseline <i>S. haematobium</i> infection intensity and demographic characteristics of initial and post-treatment follow-up cohorts.

<p>Geometric mean and 95% confidence interval are shown for age and <i>S. haematobium</i> infection intensity.</p

Multiplex PCR for bacterial, viral and protozoal pathogens in persistent diarrhoea or persistent abdominal pain in Côte d'Ivoire, Mali and Nepal

In contrast to acute diarrhoea, the aetiology of persistent digestive disorders (≥14 days) is poorly understood in low-resource settings and conventional diagnostic approaches lack accuracy. In this multi-country study, we compared multiplex real-time PCR for enteric bacterial, parasitic and viral pathogens in stool samples from symptomatic patients and matched asymptomatic controls in Côte d’Ivoire, Mali and Nepal. Among 1826 stool samples, the prevalence of most pathogens was highest in Mali, being up to threefold higher than in Côte d’Ivoire and up to tenfold higher than in Nepal. In all settings, the most prevalent bacteria were EAEC (13.0–39.9%) and Campylobacter spp. (3.9–35.3%). Giardia intestinalis was the predominant intestinal protozoon (2.9–20.5%), and adenovirus 40/41 was the most frequently observed viral pathogen (6.3–25.1%). Signifcantly diferent prevalences between symptomatic and asymptomatic individuals were observed for Campylobacter, EIEC and ETEC in the two African sites, and for norovirus in Nepal. Multiple species pathogen infection was common in Côte d’Ivoire and Mali, but rarely found in Nepal. We observed that molecular testing detected multiple enteric pathogens and showed low discriminatory accuracy to distinguish between symptomatic and asymptomatic individuals. Yet, multiplex PCR allowed for direct comparison between diferent countries and revealed considerable setting-specifcity

Multiplex PCR for bacterial, viral and protozoal pathogens in persistent diarrhoea or persistent abdominal pain in Côte d’Ivoire, Mali and Nepal

Abstract In contrast to acute diarrhoea, the aetiology of persistent digestive disorders (≥ 14 days) is poorly understood in low-resource settings and conventional diagnostic approaches lack accuracy. In this multi-country study, we compared multiplex real-time PCR for enteric bacterial, parasitic and viral pathogens in stool samples from symptomatic patients and matched asymptomatic controls in Côte d’Ivoire, Mali and Nepal. Among 1826 stool samples, the prevalence of most pathogens was highest in Mali, being up to threefold higher than in Côte d’Ivoire and up to tenfold higher than in Nepal. In all settings, the most prevalent bacteria were EAEC (13.0–39.9%) and Campylobacter spp. (3.9–35.3%). Giardia intestinalis was the predominant intestinal protozoon (2.9–20.5%), and adenovirus 40/41 was the most frequently observed viral pathogen (6.3–25.1%). Significantly different prevalences between symptomatic and asymptomatic individuals were observed for Campylobacter, EIEC and ETEC in the two African sites, and for norovirus in Nepal. Multiple species pathogen infection was common in Côte d’Ivoire and Mali, but rarely found in Nepal. We observed that molecular testing detected multiple enteric pathogens and showed low discriminatory accuracy to distinguish between symptomatic and asymptomatic individuals. Yet, multiplex PCR allowed for direct comparison between different countries and revealed considerable setting-specificity