• a. What is the immunologic basis for the reduced vaccine effectiveness in Malawian children vaccinated with rotavirus vaccine?
    b. Which rotavirus strains are circulating in Malawi and what is the impact of vaccine introduction on their evolution?
    c. Which arboviruses are circulating in Malawi and what is their burden of disease?
    d. What are the prevalence/incidence rates, and molecular characteristics of hepatitis viruses in Malawi?
    e. Is a cure possible for hepatitis infection in low income countries including Malawi?
  • a.      Rotavirus vaccine effectiveness (VE) is setting dependent as observed VE is over 90% in developed countries compared to around 60% in low-income settings where the highest burden of disease occurs. However, it is not known why there is a differential impact of rotavirus vaccines.

    b.      Wide rotavirus strains have been circulating in Malawi in the past two decades. It is not completely understood whether the monovalent vaccine currently in use in Malawi will completely cross-protect against all these strains and what will be the impact of vaccine use on the evolution of various circulating wild type rotavirus strains.

    c.       Sporadic reports from suggest that flaviviruses are circulating in Malawi due to the detection of antibody to Zika, Chikungunya, Dengue viruses in febrile patients. In addition, there has been in increase in detection of acute non-malaria febrile cases of which their causative agents are unknown.

    d.      Viral hepatitis, simply an inflammation of the liver is primarily caused by five unrelated hepatotropic viruses (i.e. hepatitis virus A, B, C, D, and E). They are known to cause mild, acute, or occasionally severe chronic infections. Although these viruses cause liver inflammation, their pathogenesis, mechanisms of resistance, and genetic classifications are different. Liver-related deaths due to complications of chronic hepatitis, cirrhosis, and hepatocellular carcinoma are widely common.
  • a.      What is the immunologic basis for the reduced vaccine effectiveness in Malawian children vaccinated with rotavirus vaccine?

            i.      To characterise B-cell subsets and immunoglobulin sequence repertoires in infants immunized with human rotavirus vaccine in Malawi

            ii.      To determine whether the presence of neutralizing maternal antibodies relate to failure to seroconvert

           iii.      To determine whether the level of neutralizing antibodies related to the frequency and functionality of RV-specific T Cells

    b.      Which rotavirus strains are circulating in Malawi?

              i.      To molecularly characterise rotavirus strains circulating in Malawi post vaccine introduction

              ii.      To determine the impact of vaccine introduction on the evolution of circulating rotavirus strains

    c.       Which arboviruses are circulating in Malawi?

         i.      Map vectors of arboviruses and estimate the incidence of arbovirus infections in febrile human cases in Malawi

         ii.      Understand the biology of circulating arboviruses through next generation sequencing studies.

         iii.      Investigate immunological profile elicited by arbovirus infection in Malawian population.

    d.      What are the prevalence/incidence rates, and molecular characteristics of hepatitis viruses in Malawi?

       i.      Determine the epidemiological and molecular characterisation of hepatitis viruses among non-remunerated blood donors screened at MBTS; and other risk groups in Malawi.
     ii.      To assess the HBV, HCV, and HIV false positivity rate among same cohort of blood donors.

    e.      Is a cure possible for hepatitis infection in low income countries including Malawi?

      i.      To assess the sustained virological response rate for hepatitis patients treated with interferon based therapy in Malawi.

      ii.      To provide convincing data to support formulation of cost-effective hepatitis virus diagnosis and treatment options in Malawi.
  • i. Bennett A, Pollock L, Jere KC, Pitzer VE, Parashar U, Tate JE, Heyderman RS, Mwansambo C, French N, Nakagomi O, Iturriza-Gomara M, Everett D, Cunliffe NA, Bar-Zeev N; VacSurv Direct and possible indirect effects of vaccination on rotavirus hospitalisations among children in Malawi four years after programmatic introduction. Vaccine. 2018 Jun 7. pii: S0264-410X(18)30513-9. doi: 10.1016/j.vaccine.2018.04.030. [Epub ahead of print]

    ii. Jere KC, Chaguza C, Bar-Zeev N, Lowe J, Peno C, Kumwenda B, Nakagomi O, Tate JE, Parashar UD, Heyderman RS, French N, Cunliffe NA, Iturriza-Gomara M. Emergence of Double- and Triple-Gene Reassortant G1P[8] Rotaviruses Possessing a DS-1-Like Backbone after Rotavirus Vaccine Introduction in Malawi. J Virol. 2018 Jan 17;92(3). pii: e01246-17. doi: 10.1128/JVI.01246-17. Print 2018 Feb 1.

    iii. Bwogi J, Jere KC, Karamagi C, Byarugaba DK, Namuwulya P, Baliraine FN, Desselberger U, Iturriza-Gomara M. Whole genome analysis of selected human and animal rotaviruses identified in Uganda from 2012 to 2014 reveals complex genome reassortment events between human, bovine, caprine and porcine strains. PLoS One. 2017 Jun 22;12(6):e0178855. doi: 10.1371/journal.pone.0178855. eCollection 2017.

    iv. Hull JJ, Cunliffe N, Jere KC, Moon SS, Wang Y, Parashar U, Jiang B. Rotavirus antigen, cytokine, and neutralising antibody profiles in sera of children with and without HIV infection in Blantyre, Malawi. Malawi Med J. 2017 Mar;29(1):24-28.

    v. Nakagomi T, Do LP, Agbemabiese CA, Kaneko M, Gauchan P, Doan YH, Jere KC, Steele AD, Iturriza-Gomara M, Nakagomi O, Cunliffe NA. Whole-genome characterisation of G12P[6] rotavirus strains possessing two distinct genotype constellations co-circulating in Blantyre, Malawi, 2008. Arch Virol. 2017 Jan;162(1):213-226. doi: 10.1007/s00705-016-3103-5. Epub 2016 Oct 7.

    vi. Arana A, Montes M, Jere KC, Alkorta M, Iturriza-Gómara M, Cilla G. Emergence and spread of G3P[8] rotaviruses possessing an equine-like VP7 and a DS-1-like genetic backbone in the Basque Country (North of Spain), 2015. Infect Genet Evol. 2016 Oct;44:137-144. doi: 10.1016/j.meegid.2016.06.048. Epub 2016 Jun 28.

    vii. Bar-Zeev N, Tate JE, Pecenka C, Chikafa J, Mvula H, Wachepa R, Mwansambo C, Mhango T, Chirwa G, Crampin AC, Parashar UD, Costello A, Heyderman RS, French N, Atherly D, Cunliffe NA; VACSURV Consortium. Cost-Effectiveness of Monovalent Rotavirus Vaccination of Infants in Malawi: A Postintroduction Analysis Using Individual Patient-Level Costing Data. Clin Infect Dis. 2016 May 1;62 Suppl 2:S220-8. doi: 10.1093/cid/civ1025.
  • Prof Nigel Cunliffe (University of Liverpool), Prof Miren Iturriza-Gomara (University of Liverpool), Prof Carl Goodyear (University of Glasgow), Prof Gagandeep Kang (Christian Medical College, Vellore), Prof Mapaseka Seheri (Diarrhoea Pathogens Research Unit, Medunsa, Pretoria), Prof Geoffrey Mpahlele (Medical Research Council of South Africa), Dr Al Leslie (AHRI), Prof Trudi O’Neill (University of Free State), Prof Felicity Burt (University of Free State), Dr Martin Nyaga (University of Free State), Dr Francis Denis (University of Ghana), Dr Valentine Ndze (University of Yaonde), Dr Carl Anderson (Sanger Institute), Prof Carl Kirkwood (BMGF), Prof Julie Bines (MCRI, Melbourne), Prof Katie Flanagan (RMIT).