A human in vitro model system for investigating genome-wide host responses to SARS coronavirus infection

Background

Schistosoma mansoni and Plasmodium falciparum are common infections of school aged children in Kenya. They both cause enlargement of the spleen, but their relative contribution to the condition of splenomegaly remains unknown in areas where both infections are endemic. Here, we have investigated whether relatively high exposure to both infections has a clinically measurable effect on this condition.

Methods

96 children aged 6–16 years living along a ten kilometre stretch and within 4 km south of a river that is a source of both S. mansoni and malaria infections were examined clinically for splenomegaly along the mid clavicular line (MCL) and mid axillary line (MAL). The survey was conducted outside the malaria transmission season. The consistency of the organ was recorded as soft, firm or hard. Mapping of the locations of houses and the course of the river was undertaken. Egg counts were mapped at the household level, as were IgG3 responses to Plasmodium falciparum schizont antigen (anti-Pfs IgG3), in order to identify areas with relatively high exposure to both infections, either infection or neither infection. ANOVA was used to test for differences in egg counts, IgG3 levels and the magnitude of spleen enlargement between these areas.

Results

4 contiguous sectors were identified, one where anti-Pfs IgG3 responses and S. mansoni egg counts were both high, one where only anti-Pfs IgG3 responses were high, one where only egg counts were high, and one where both anti-Pfs IgG3 responses and egg counts were low. Spleen MAL and MCL values were significantly higher amongst children from the sector with highest IgG3 levels and highest egg counts but similar amongst children from elsewhere. Both egg counts and anti-Pfs IgG3 responses were significantly higher in children with MAL values >=4 cm. Hardening of spleens was associated with proximity of domicile to the river.

Conclusions

Micro-geographical variation in exposure to S. mansoni and malaria infections can be exploited to investigate the chronic impact of these two infections. These results provide firm evidence that relatively high exposure to both infections exacerbates splenomegaly even outside the malaria transmission season. Major implications include assessing the burden of infection in school age-children.