Schistosomiasis is a water-borne parasitic disease of great public health importance mainly
in sub-Saharan African countries. The majority of current control programmes use the
antihelminthic drug praziquantel to reduce disease burden in endemic areas. Praziquantel
treatment has been reported to accelerate the development of protective immunity against
re-infection that otherwise takes years to develop. To date, there is no licensed vaccine for
schistosomiasis in humans but an attenuated schistosome parasite vaccine has been tested in
animal models.
Employing systematic review and meta-analysis approaches, my PhD research has four main
objectives relating to attenuated schistosome vaccine and praziquantel treatment: 1) to
identify predictors that determine protection levels after treatment with attenuated
Schistosoma mansoni vaccines in the mouse model, 2) to quantify the influence of host and
schistosome parasite species on attenuated parasite vaccine efficacy, 3) to explore the
direction of change (increase/decrease) in schistosome parasite-specific antibody isotypes
after praziquantel treatment in humans, 4) to identify predictors of praziquantel efficacy in
humans.
My analyses revealed three factors that have an influence on the protection levels provided
by attenuated schistosome parasite vaccines: increasing numbers of immunizing parasites
had a positive effect on the levels of protection whereas increasing the radiation dose and the
time to challenge infection had negative effects. Analyses showed that the attenuated
schistosome vaccine has the potential to achieve protection levels as high as 79% after a
single dose in mice. Alongside this, baboon studies consistently reported protective effects of
attenuated schistosome vaccines against re-infection. These results show there is a high
potential for an attenuated schistosome parasite vaccine to be effective in humans.
A meta-analysis of the influence of praziquantel treatment on the direction of change in
schistosome-specific antibody isotypes was conducted. The analysis revealed considerable
variability in the antibodies’ direction of change among populations. The results also
demonstrated an increase of anti-worm IgA and IgE in the majority of studies. These
antibodies have been reported to have a protective effect against re-infection. The
combination of age and infection intensity, and the number of days after treatment were
identified as influential predictors for some antibody isotypes, but there was no single
predictor that consistently affected all antibody isotypes in the same way.
Praziquantel efficacy levels in humans were investigated and the analyses revealed that cure
rates for schistosomiasis increase with praziquantel dose, and were affected by the identity of
the schistosome parasite species (S. mansoni vs. S. haematobium) and the age of the
participants (children: 0-19 years old vs. adults: ≥ 20 years old). There has been no clear
efficacy level reduction over the treatment years (1979-2013) suggesting that praziquantel is
still effective in the treatment of schistosomiasis despite concerns about possible resistance.
The development of a schistosome vaccine will benefit from a closer investigation into the
mechanisms through which protection is acquired in attenuated schistosome parasite vaccine
studies showing high potential efficacy in animal models. Nevertheless, it will take time to
develop a schistosome vaccine for human use. The uptake of the vaccine will be made even
more challenging by the lack of adequate infrastructure in schistosomiasis endemic areas. In
the meantime, close monitoring of praziquantel efficacy levels is necessary to confirm the
effectiveness of schistosomiasis control in endemic areas
