T cell-mediated immunity in CBA mice during Schistosoma japonicum infection.

Characterisation of the cellular immune response to schistosomiasis is well established for Schistosoma mansoni but a comprehensive description of T cell-mediated immune responses against S. japonicum infection is lacking. Accordingly, 20 CBA mice were infected with cercariae of S. japonicum and the immune response at different time points was determined. Mouse spleen and liver lymphocytes were isolated from the mice and stimulated with schistosomal adult worm antigen preparation (SWAP) and schistosomal soluble egg antigen (SEA). There was a relatively higher Th1 immune response to SWAP compared to SEA at the early phase of infection (up to week 5 post challenge). However, a Th2 immune response directed against SEA was dominant at week 6 post-infection, a time point when the highest IgG response against both SWAP and, especially, SEA was generated. The regulatory immune response was highest at the early phase of the immune response (up to week 5 post challenge) followed by a rapid decline at week 6-post infection. Before egg-laying, S. japonicum induced a regulatory T cell immune response which may limit the early Th1-mediated immune response that is believed to be protective in murine schistosomiasis. Following egg laying, the immune response was polarized to a Th2 immune response mainly directed against the eggs and this may contribute to parasite survival.

Correction to: Schistosomiasis-from immunopathology to vaccines.

The original version of this article inadvertently missed out to display the correct acknowledgement for Fig. 2. The corrected part of legend of Fig. 2 is given below.

Schistosomiasis-from immunopathology to vaccines.

Schistosomiasis (bilharzia) is a neglected tropical disease caused by trematode worms of the genus Schistosoma. The transmission cycle involves human (or other mammalian) water contact with surface water contaminated by faeces or urine, as well as specific freshwater snails acting as intermediate hosts. The main disease-causing species are S. haematobium, S. mansoni and S. japonicum. According to the World Health Organisation, over 250 million people are infected worldwide, leading to considerable morbidity and the estimated loss of 1.9 million disability-adjusted life years (DALYs), a likely underestimated figure. Schistosomiasis is characterised by focal epidemiology and an over-dispersed population distribution, with higher infection rates in children. Complex immune mechanisms lead to the slow acquisition of immune resistance, but innate factors also play a part. Acute schistosomiasis, a feverish syndrome, is most evident in travellers following a primary infection. Chronic schistosomiasis affects mainly individuals with long-standing infections residing in poor rural areas. Immunopathological reactions against schistosome eggs trapped in host tissues lead to inflammatory and obstructive disease in the urinary system (S. haematobium) or intestinal disease, hepatosplenic inflammation and liver fibrosis (S. mansoni and S. japonicum). An effective drug-praziquantel-is available for treatment but, despite intensive efforts, no schistosomiasis vaccines have yet been accepted for public use. In this review, we briefly introduce the schistosome parasites and the immunopathogenic manifestations resulting from schistosomiasis. We then explore aspects of the immunology and host-parasite interplay in schistosome infections paying special attention to the current status of schistosomiasis vaccine development highlighting the advancement of a new controlled human challenge infection model for testing schistosomiasis vaccines.

Schistosome Vaccines for Domestic Animals.

Schistosomiasis is recognized as a tropical disease of considerable public health importance, but domestic livestock infections due to Schistosoma japonicum, S. bovis, S. mattheei and S. curassoni are often overlooked causes of significant animal morbidity and mortality in Asia and Africa. In addition, whereas schistosomiasis japonica is recognized as an important zoonosis in China and the Philippines, reports of viable schistosome hybrids between animal livestock species and S. haematobium point to an underappreciated zoonotic component of transmission in Africa as well. Anti-schistosome vaccines for animal use have long been advocated as part of the solution to schistosomiasis control, benefitting humans and animals and improving the local economy, features aligning with the One Health concept synergizing human and animal health. We review the history of animal vaccines for schistosomiasis from the early days of irradiated larvae and then consider the recombinant DNA technology revolution and its impact in developing schistosome vaccines that followed. We evaluate the major candidates tested in livestock, including the glutathione S-transferases, paramyosin and triose-phosphate isomerase, and summarize some of the future challenges that need to be overcome to design and deliver effective anti-schistosome vaccines that will complement current control options to achieve and sustain future elimination goals.

In vivo efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria in Dembia District, northwest Ethiopia.

BACKGROUND: Artemether-lumefantrine (AL) has been used as a first-line treatment for uncomplicated Plasmodium falciparum malaria in Ethiopia since 2004. Antimalarial drug resistance is one of the major obstacles for malaria control and curtails the lifespan of several drugs. Thus, continued monitoring of the efficacy of AL is of great public health importance in malaria endemic areas. OBJECTIVE: This study aimed to investigate the therapeutic efficacy and safety of AL for the treatment of uncomplicated P. falciparum malaria in the Dembia district, northwest Ethiopia. METHODS: A prospective study was conducted from April 2015 to February 2016 at Kola Diba Health Center (KHC) in the Dembia district to determine the therapeutic efficacy and safety of AL for the treatment of uncomplicated P. falciparum monoinfection. Patients were treated with the six-dose regimen of AL over 3 days and followed up for 28 days as per the World Health Organization protocol. RESULTS: Of the total 80 patients enrolled in the AL efficacy study, 75 patients completed the 28 days follow-up. None of the participants reported major adverse events. No early treatment failure or late clinical failure were observed during the study, but there were 6 (8.0%) late parasitological failures. The uncorrected per protocol cure rate of AL was 92.0 (95% CI: 85.7-98.3). Treatment with AL cleared parasitemia and fever in >95% of the patients by day 3. CONCLUSION: This study showed that AL is well tolerated and remains efficacious for treatment of uncomplicated P. falciparum malaria in northwest Ethiopia. However, the observed late parasitological failures in this study are of a concern and warrant continued monitoring of drug efficacy as per the World Health Organization recommendations.

Schistosomiasis vaccines: where do we stand?

Schistosomiasis, caused mainly by S. mansoni, S. haematobium and S. japonicum, continues to be a serious tropical disease and public health problem resulting in an unacceptably high level of morbidity in countries where it is endemic. Praziquantel, the only drug currently available for treatment, is unable to kill developing schistosomes, it does not prevent re-infection and its continued extensive use may result in the future emergence of drug-resistant parasites. This scenario provides impetus for the development and deployment of anti-schistosome vaccines to be used as part of an integrated approach for the prevention, control and eventual elimination of schistosomiasis. This review considers the present status of candidate vaccines for schistosomiasis, and provides some insight on future vaccine discovery and design.