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Uganda Virus Research Institute

REPUBLIC OF UGANDA

Immune responses in Schistosoma mansoni infection and treatment using Aurora spectral flow cytometry

Dr Mawa and team in the field recruiting participants

Project title: Exploring immune responses in primary and more advanced Schistosoma mansoni infection and treatment of preschool-age children using Aurora spectral flow cytometry

Principal Investigator: Dr. Akusa Patrice Mawa

Sponsor: Uganda National Health Research Organisation

Funder: European and Developing Countries Clinical Trials Partnership (EDCTP)

Background

Up to 50 million preschool-age children (PSAC, ≤5 years old) in Africa, infected by Schistosoma mansoni (S. mansoni) are vulnerable to morbidities that affect their growth and development such as anemia, malnutrition, pervasive learning disabilities and linear growth stunting.

Immunity in schistosome infections has been mainly studied in school-age children (SAC, ≥6 years old), and adults, yet infections occur early in preschool-age. Immune responses at primary infection or during early stages of infection, especially in PSAC, are therefore poorly understood. Infections in early life have potential effects on the infant’s developing immune system and thus may determine later life outcomes. It is essential that these responses are probed and understood. 

Schistosomiasis morbidity control relies on use of praziquantel (PZQ), which alone, may not eliminate the disease. A recent model study suggests use of both MDA and vaccination to eliminate schistosomiasis, and PZQ has been demonstrated to work in synergy with the immune system of the host. The immunological responses to PZQ in PSAC are not fully understood due to current treatment guidelines, which largely exclude PSAC. This constitutes a public health inequity. 

Aim

To profile immune responses in primary and more advanced S. mansoni infection and treatment of PSAC using a state-of-the-art multi-parameter Aurora spectral flow cytometry. Using spectral flow cytometry and dimensionality reduction algorithms would provide a powerful discovery-oriented approach to characterize the phenotype and function of immune cells in PSAC, linking S. mansoni infection to vaccine-specific immune responses and immunotherapeutic targets. 

Objectives

  1. To characterize immune responses of PSAC in primary and more advanced S. mansoni infection
  2. To determine the effect of PZQ treatment of S. mansoni on immune responses in PSAC

Study design

A longitudinal cohort study nested within a phase II trial of PZQ in PSAC living in an area endemic for schistosomiaisis in Uganda. Samples will be collected before, and at 4 weeks and 6 months post treatment. Children will be categorised by intensity of infection. Some of the children who initially test negative for S. mansoni will be followed to infection. A questionnaire on demographic characteristics will be administered. Clinical assessment of primary S. mansoni infection will be conducted. Spectral flow cytometry will be performed on peripheral blood mononuclear cells. 

Significance

The data generated will expand our understanding of immune responses in S. mansoni infection and treatment of PSAC. These may have implications for vaccines or alternative immunotherapeutic interventions against schistosomiasis.

"The fellowship will allow me to be trained in the use of Aurora spectral flow cytometry and in the analysis, interpretation and presentation of complex data.

I will use the data generated to apply for further funding enabling me to establish myself as an independent researcher and a team leader."- Dr. Akusa Patrice Mawa.

Progress

The recruitment and follow-up to six (6) months of the infected children have been completed. Recruitment of the uninfected children is planned for the end of the year 2022. This will constitute the control group.