Date Published: October 16, 2014
Publisher: Public Library of Science
Author(s): Martial L. Ndeffo Mbah, Laura Skrip, Scott Greenhalgh, Peter Hotez, Alison P. Galvani, Judd L. Walson. http://doi.org/10.1371/journal.pntd.0003234
Abstract: BackgroundSub-Saharan Africa harbors the majority of the global burden of malaria and schistosomiasis infections. The co-endemicity of these two tropical diseases has prompted investigation into the mechanisms of coinfection, particularly the competing immunological responses associated with each disease. Epidemiological studies have shown that infection with Schistosoma mansoni is associated with a greater malaria incidence among school-age children.MethodologyWe developed a co-epidemic model of malaria and S. mansoni transmission dynamics which takes into account key epidemiological interaction between the two diseases in terms of elevated malaria incidence among individuals with S. mansoni high egg output. The model was parameterized for S. mansoni high-risk endemic communities, using epidemiological and clinical data of the interaction between S. mansoni and malaria among children in sub-Saharan Africa. We evaluated the potential impact of the S. mansoni–malaria interaction and mass treatment of schistosomiasis on malaria prevalence in co-endemic communities.Principal FindingsOur results suggest that in the absence of mass drug administration of praziquantel, the interaction between S. mansoni and malaria may reduce the effectiveness of malaria treatment for curtailing malaria transmission, in S. mansoni high-risk endemic communities. However, when malaria treatment is used in combination with praziquantel, mass praziquantel administration may increase the effectiveness of malaria control intervention strategy for reducing malaria prevalence in malaria- S. mansoni co-endemic communities.Conclusions/SignificanceSchistosomiasis treatment and control programmes in regions where S. mansoni and malaria are highly prevalent may have indirect benefits on reducing malaria transmission as a result of disease interactions. In particular, mass praziquantel administration may not only have the direct benefit of reducing schistosomiasis infection, it may also reduce malaria transmission and disease burden.
Partial Text: Malaria is highly endemic throughout sub-Saharan Africa in which 85% of global malaria cases and 90% of malaria deaths occur . Schistosoma mansoni (the causative agent of intestinal schistosomiasis) is likewise prevalent in many sub-Saharan African countries , , accounting for approximately one-third of the total cases of schistosomiasis in the region . Both malaria and intestinal schistosomiasis share similar epidemiological distributions and present challenges to public health and socio-economic development throughout these regions . Due to their coendemicity, there has been increased investigation into the interactive pathology between malaria and S. mansoni–.
To quantify the potential impact of S. mansoni infection and mass praziquantel administration on malaria transmission, we developed a compartmental deterministic model for co-endemic communities in sub-Saharan Africa. Specifically, our model describes the joint dynamics of malaria and S. mansoni transmission among children younger than 15 years old. This age group is the most at risk for both malaria and schistosomiasis transmission in sub-Saharan Africa .
By comparing malaria prevalence in the presence and absence of S. mansoni co-endemicity, we showed that the impact of schistosomiasis co-infection on increasing malaria prevalence was higher in areas of low malaria transmission than areas of high malaria transmission (Figures 1 & S1). For example, disease interaction was shown to increase malaria prevalence by 3.0–4.5% for an AEIR of 10 ibpy and by 0.6–1.5% for an AEIR of 100 ibpy, depending on malaria treatment coverage, ranging from 30–90% (Figure 1). The effect of S. mansoni co-infection on malaria prevalence plateaued from 100 ibpy upwards (Figure 1).
We developed a co-epidemic model of malaria and S. mansoni transmission dynamics to take into account elevated susceptibility to malaria mediated by S. mansoni infection. We used this model to investigate the potential effect of malaria-S. mansoni interaction on the effectiveness of ACT and mass praziquantel administration for schistosomiasis for reducing malaria prevalence in co-endemic communities. Our results suggested that co-infection with schistosomiasis in low malaria transmission settings increases malaria prevalence. We further showed that in the absence of mass praziquantel administration, the interaction between S. mansoni and malaria may have contributed to reductions in population-level effectiveness of malaria treatment in areas of stable malaria transmission. In regions of low malaria treatment coverage, co-infection with schistosomiasis led to the greatest increase in per person malaria episodes, independent of whether malaria transmission was high or low. Our finding is consistent with epidemiological observations and laboratory studies that have suggested that presence of S. mansoni infections may affect the efficacy of malaria control measures, including a potential vaccine in co-endemic communities , . The interaction between the two diseases may increase the health benefits of mass praziquantel administration by generating the additional indirect benefit of reducing malaria transmission in co-endemic communities. Our results indicated that this benefit was particularly strong in low malaria transmission regions that experienced increased malaria susceptibility due to schistosomiasis co-infection. Malaria is associated with a Th1 immune response , while S. mansoni infection is associated with a Th2 response and had been demonstrated to impair immune responses to malaria , . By reducing S. mansoni worm burden of infected individuals, praziquantel treatment may reduce the Th2 immune response associated with S. mansoni infection which may in turn result in a shift in the Th1/Th2 immune balance ,  towards the Th1 response that protects against malaria parasite. Though our study focused on Plasmodium falciparum, our results may be applicable to other forms of malaria such as Plasmodium ovale and Plasmodium vivax, which may also interact with S. mansoni. Prototype vaccines for both malaria  and S. mansoni intestinal schistosomiasis  are under development, such that the two vaccines could be co-formulated or combined . Our results suggest that a co-formulated or combined vaccine may be more efficacious in reducing malaria transmission in S. mansoni endemic communities than a vaccine targeting malaria alone.