Vaccine Studies: Clinical Trials for Enteric Virus Vaccines
Diarrhoea is the second-leading cause of death worldwide among children under the age of five, killing an estimated three quarters of a million children annually and hospitalizing millions more, mostly in developing countries. The most common cause of severe childhood diarrhoea is rotavirus. It is responsible for up to 40% of deaths from diarrhoea, resulting in excess of 200,000 deaths in children younger than five years old globally, followed by Shigella causing 212,000 deaths, Norovirus (200,000 deaths), Vibrio cholerae (107,000 deaths), Adenovirus (93,000 deaths), non-typhoidal Salmonella (NTS) (87,000 deaths), Campylobacter (75,000 deaths), Cryptosporidium (57,000 deaths), and enterotoxigenic Escherichia coli (ETEC) (51,000 deaths). Vaccination offers the best hope for protecting all infants, regardless of economic status against diarrhoea disease and remains an effective public health strategy recommended by the WHO to reduce the burden of severe infections.
Our research interest includes evaluating the efficacy of the different rotavirus vaccines against severe acute gastroenteritis in Ghana in the first two years of life, as well as in the first and second years of life, separately. We are also interested in assessing the impact of vaccine introduction on acute gastroenteritis hospitalizations as well as estimating vaccine effectiveness of any current rotavirus vaccines introduced into the country’s National Expanded Immunization Programme. Our research also focuses on Post-marketing intussusception monitoring after the introduction of any oral rotavirus vaccines in Ghana. Because oral rotavirus vaccines typically display lower efficacy in low- and middle -income countries as compared to developed countries, we are also interested in assessing the efficacy, safety and immunogenicity of parenterally administered rotavirus vaccine in children.
Through the establishment of various rotavirus surveillance sentinel sites across the country, we were able to provide evidence of the burden of rotavirus-associated gastroenteritis among Ghanaian children. We were also able to show through various clinical trials that yes, rotavirus vaccines worked in Ghana. This “country-owned” evidence-based data on the burden of rotavirus disease and epidemiology as well as the data generated from the different clinical trials made it possible for the advocacy and demand for the introduction of rotavirus vaccines into the National immunization programme which was successfully implemented in April 2012. Through post-marketing intussusception monitoring, we were also able to show that these vaccines were safe when used in the first year of life of the Ghanaian child. We generated a lot of data on the economic impact (how much you spend if you take off vaccination, and how much you save because of vaccination) and the cost benefits of vaccination.
- A Phase 3 double-blind, randomized, active comparator-controlled, group-sequential, multinational trial to assess the safety, immunogenicity and efficacy of a trivalent P2-VP8 subunit rotavirus vaccine in prevention of severe rotavirus gastroenteritis in healthy infants (2021 – to date)
- Evaluation of the impact and effectiveness of Rotavac rotavirus vaccine in Ghana (2021 – to date)
- Post-marketing intussusception monitoring after introduction of oral rotavirus vaccines in Ghana. (2018 – to date)
- Model-guided assessment of rotavirus vaccine impact in developing countries (2021- to date)
- Effectiveness of the monovalent rotavirus vaccine (RotarixTM) against severe rotavirus diarrhea in Ghana (2013- 2020)
- Correlation between histo-blood group antigens (HBGAs) and serum antibody response to rotavirus vaccine in Ghanaian children (2016 – 2019)
- Nested case-control analysis of the influence of the microbiome on human rotavirus vaccine (RotarixTM) immunogenic response in infants in rural Ghana (2016 – 2019)
- Efficacy, immunogenicity, and safety of two doses of a tetravalent rotavirus vaccine RRV-TV in Ghana (2009)
- Kim AH, Armah G, Dennis F, Wang L, Rodgers R, Droit L, Baldridge MT, Handley SA, Harris VC. 2022. Enteric virome negatively affects seroconversion following oral rotavirus vaccination in a longitudinally sampled cohort of Ghanaian infants. Cell Host Microbe 30:110-123 e5.
- Glover-Addy H, Ansong D, Enweronu-Laryea C, Tate JE, Amponsa-Achiano K, Sarkodie B, Mwenda JM, Diamenu S, Owusu SK, Nimako B, Mensah NK, Armachie J, Narh C, Pringle K, Grytdal SP, Binka F, Lopman B, Parashar UD, Armah G. 2021. Epidemiology of intussusception in infants less than one year of age in Ghana, 2012-2016. Pan Afr Med J 39:8.
- Pindyck T, Parashar U, Mwenda JM, Tadesse A, Armah G, Omore R, Ngwira B, Jani B, Mpabalwani EM, Mbuwayesango B, Tate J, African Intussusception Surveillance N. 2020. Risk Factors Associated With Increased Mortality From Intussusception in African Infants. J Pediatr Gastroenterol Nutr 70:20-24.
- Armah GE, Cortese MM, Dennis FE, Yu Y, Morrow AL, McNeal MM, Lewis KDC, Awuni DA, Armachie J, Parashar UD. 2019. Rotavirus Vaccine Take in Infants Is Associated With Secretor Status. J Infect Dis 219:746-749.
- Pindyck T, Tate JE, Bonkoungou IJO, Armah G, Mujuru HA, Rugambwa C, Mwenda JM, Parashar U. 2019. Timeliness of rotavirus vaccination at sentinel sites in four early-adopter African countries. Vaccine 37:6002-6007.
- Enweronu-Laryea CC, Armah G, Sagoe KW, Ansong D, Addo-Yobo E, Diamenu SK, Mwenda JM, Parashar UD, Tate JE. 2018. Sustained impact of rotavirus vaccine introduction on rotavirus gastroenteritis hospitalizations in children <5years of age, Ghana, 2009-2016. Vaccine doi:10.1016/j.vaccine.2018.02.058.
- Tate JE, Mwenda JM, Armah G, Jani B, Omore R, Ademe A, Mujuru H, Mpabalwani E, Ngwira B, Cortese MM, Mihigo R, Glover-Addy H, Mbaga M, Osawa F, Tadesse A, Mbuwayesango B, Simwaka J, Cunliffe N, Lopman BA, Weldegebriel G, Ansong D, Msuya D, Ogwel B, Karengera T, Manangazira P, Bvulani B, Yen C, Zawaira FR, Narh CT, Mboma L, Saula P, Teshager F, Getachew H, Moeti RM, Eweronu-Laryea C, Parashar UD, African Intussusception Surveillance N. 2018. Evaluation of Intussusception after Monovalent Rotavirus Vaccination in Africa. N Engl J Med 378:1521-1528.
- Troeger C, Khalil IA, Rao PC, Cao S, Blacker BF, Ahmed T, Armah G, Bines JE, Brewer TG, Colombara DV, Kang G, Kirkpatrick BD, Kirkwood CD, Mwenda JM, Parashar UD, Petri WA, Jr., Riddle MS, Steele AD, Thompson RL, Walson JL, Sanders JW, Mokdad AH, Murray CJL, Hay SI, Reiner RC, Jr. 2018. Rotavirus Vaccination and the Global Burden of Rotavirus Diarrhea Among Children Younger Than 5 Years. JAMA Pediatr doi:10.1001/jamapediatrics.2018.1960.
- Nonvignon J, Atherly D, Pecenka C, Aikins M, Gazley L, Groman D, Narh CT, Armah G. 2018. Cost-effectiveness of rotavirus vaccination in Ghana: Examining impacts from 2012 to 2031. Vaccine 36:7215-7221.
- Harris VC, Armah G, Fuentes S, Korpela KE, Parashar U, Victor JC, Tate J, de Weerth C, Giaquinto C, Wiersinga WJ, Lewis KD, de Vos WM. 2017. Significant Correlation Between the Infant Gut Microbiome and Rotavirus Vaccine Response in Rural Ghana. J Infect Dis 215:34-41.
- Nonvignon J, Atherly D, Pecenka C, Aikins M, Gazley L, Groman D, Narh CT, Armah G. 2017. Cost-effectiveness of rotavirus vaccination in Ghana: Examining impacts from 2012 to 2031. Vaccine doi:10.1016/j.vaccine.2017.11.080.
- Armah G, Pringle K, Enweronu-Laryea CC, Ansong D, Mwenda JM, Diamenu SK, Narh C, Lartey B, Binka F, Grytdal S, Patel M, Parashar U, Lopman B. 2016. Impact and Effectiveness of Monovalent Rotavirus Vaccine Against Severe Rotavirus Diarrhea in Ghana. Clin Infect Dis 62 Suppl 2:S200-7.
- Armah G, Lewis KD, Cortese MM, Parashar UD, Ansah A, Gazley L, Victor JC, McNeal MM, Binka F, Steele AD. 2016. A Randomized, Controlled Trial of the Impact of Alternative Dosing Schedules on the Immune Response to Human Rotavirus Vaccine in Rural Ghanaian Infants. J Infect Dis doi:10.1093/infdis/jiw023.
- Armah GE, Binka FN. 2014. Sustaining rotavirus vaccination in Africa: measuring vaccine effectiveness. Lancet Infect Dis 14:1031-2.
- Enweronu-Laryea CC, Boamah I, Sifah E, Diamenu SK, Armah G. 2014. Decline in severe diarrhea hospitalizations after the introduction of rotavirus vaccination in Ghana: a prevalence study. BMC Infect Dis 14:431.
- Armah GE, Kapikian AZ, Vesikari T, Cunliffe N, Jacobson RM, Burlington DB, Ruiz LP, Jr. 2013. Efficacy, immunogenicity, and safety of two doses of a tetravalent rotavirus vaccine RRV-TV in Ghana with the first dose administered during the neonatal period. J Infect Dis 208:423-31.
- Abbott C, Tiede B, Armah G, Mahmoud A. 2012. Evaluation of cost-effectiveness of live oral pentavalent reassortant rotavirus vaccine introduction in Ghana. Vaccine 30:2582-7.
- Armah GE, Breiman RF, Tapia MD, Dallas MJ, Neuzil KM, Binka FN, Sow SO, Ojwando J, Ciarlet M, Steele AD. 2012. Immunogenicity of the pentavalent rotavirus vaccine in African infants. Vaccine 30 Suppl 1:A86-93.
- Breiman RF, Zaman K, Armah G, Sow SO, Anh DD, Victor JC, Hille D, Ciarlet M, Neuzil KM. 2012. Analyses of health outcomes from the 5 sites participating in the Africa and Asia clinical efficacy trials of the oral pentavalent rotavirus vaccine. Vaccine 30 Suppl 1:A24-9.
- Tapia MD, Armah G, Breiman RF, Dallas MJ, Lewis KD, Sow SO, Rivers SB, Levine MM, Laserson KF, Feikin DR, Victor JC, Ciarlet M, Neuzil KM, Steele AD. 2012. Secondary efficacy endpoints of the pentavalent rotavirus vaccine against gastroenteritis in sub-Saharan Africa. Vaccine 30 Suppl 1:A79-85.
- Armah GE, Sow SO, Breiman RF, Dallas MJ, Tapia MD, Feikin DR, Binka FN, Steele AD, Laserson KF, Ansah NA, Levine MM, Lewis K, Coia ML, Attah-Poku M, Ojwando J, Rivers SB, Victor JC, Nyambane G, Hodgson A, Schodel F, Ciarlet M, Neuzil KM. 2010. Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomised, double-blind, placebo-controlled trial. Lancet 376:606-14.
- Arvay ML, Curns AT, Terp S, Armah G, Wontuo P, Parashar UD, Binka F, Glass RI, Widdowson MA. 2009. How much could rotavirus vaccines reduce diarrhea-associated mortality in northern Ghana? A model to assess impact. J Infect Dis 200 Suppl 1:S85-91.