Co-administration study in South African infants of a live-attenuated oral human rotavirus vaccine (RIX4414) and poliovirus vaccines

A double-blind, placebo-controlled phase II trial (e-Track 444563-014/NCT00346892) was conducted in South Africa to evaluate the co-administration of RIX4414 (live-attenuated human G1P[8] rotavirus vaccine) and oral poliovirus vaccine (OPV) administered simultaneously. Healthy infants (n=450) were randomized into three groups (RIX4414+OPV, RIX4414+IPV or Placebo+OPV) to receive two oral doses of RIX4414/placebo with OPV or IPV using two vaccination schedules (6-10 weeks and 10-14 weeks). Serum anti-rotavirus IgA antibodies (ELISA) and neutralizing antibodies (micro-neutralization assay) to poliovirus serotypes 1, 2 and 3 were measured. Co-administration of RIX4414 with OPV did not result in a decrease in the high sero-protection rates against poliovirus serotypes 1, 2 and 3 detected after the third OPV dose (98-100%). The anti-rotavirus IgA antibody sero-conversion rates were higher for the 10-14 weeks schedule (55-61%) compared to the 6-10 weeks schedule (36-43%). Solicited symptoms were reported at similar rates between RIX4414 and placebo groups and no serious adverse events related to RIX4414 were reported. This study provided evidence that RIX4414 can be co-administered with routine EPI immunizations including OPV and that two doses of RIX4414 were well tolerated and immunogenic in South African infants.     

Impact of rotavirus vaccine on rotavirus diarrhoea in countries of East and Southern Africa

BackgroundEstablished in 2006 with four countries conducting hospital-based rotavirus surveillance, the African rotavirus surveillance network has expanded over subsequent years. By 2015, 14 countries in the World Health Organization (WHO) East and Southern Africa sub-region (Eritrea, Ethiopia, Kenya, Lesotho, Madagascar, Mauritius, Namibia, Rwanda, Seychelles, Swaziland, Tanzania, Uganda, Zambia and Zimbabwe) were participating in the rotavirus surveillance network coordinated by WHO. We monitored the proportion of rotavirus diarrhoea among children under five years of age who were hospitalized for diarrhoea in the sentinel hospitals from 2010 to 2015 among countries that introduced rotavirus vaccine during or before 2013 (Rwanda, Tanzania, Zambia and Ethiopia) and compared with the other countries in the network.MethodsChildren under the age of five years hospitalized due to acute diarrhoea were enrolled into the sentinel surveillance system and had stool samples collected and tested for rotavirus antigens by enzyme immunoassay. We described trends in rotavirus positivity among tested stool samples before and after rotavirus vaccine introduction.ResultsIn countries that introduced rotavirus vaccine by 2013 (Rwanda, Tanzania, Zambia and Ethiopia), average rotavirus vaccine coverage from 2010 to 2015 improved from 0% in 2010 and 2011, 13% in 2012, 46% in 2013, 83% in 2014 to 90% in 2015. Annual average rotavirus positivity from 2010 to 2015 was 35%, 33%, 38%, 28%, 27%, and 19%, respectively. In countries that introduced rotavirus vaccine after 2013 or had not introduced by 2015, average rotavirus vaccine coverage was 0% in 2010–2013, 13% in 2014 and 51% in 2015. In these countries, rotavirus positivity was 44% in 2010, 32% in 2011, 33% in 2012, 41% in 2013, 40% in 2014 and 25% in 2015.ConclusionCountries that introduced rotavirus vaccine by 2013 had a lower proportion of rotavirus positive hospitalizations in 2013–2015 as compared to those that had not introduced rotavirus vaccine by 2013. The decrease in rotavirus positivity was inversely related to increase in rotavirus vaccine coverage showing impact of rotavirus vaccines.     

Impact of rotavirus vaccine on all-cause diarrhea and rotavirus hospitalizations in Madagascar

BackgroundRotavirus vaccine was introduced into the Extended Program on Immunization in Madagascar in May 2014. We analyzed trends in prevalence of all cause diarrhea and rotavirus hospitalization in children <5 years of age before and after vaccine introduction and assessed trend of circulating rotavirus genotypes at Centre Hospitalier Universitaire Mère Enfant Tsaralalàna (CHU MET).MethodsFrom January 2010 to December 2016, we reviewed the admission logbook to observe the rate of hospitalization caused by gastroenteritis among 19619 children <5 years of age admitted at the hospital. In June 2013–December 2016, active rotavirus surveillance was also conducted at CHUMET with support from WHO. Rotavirus antigen was detected by EIA from stool specimen of children who are eligible for rotavirus gastroenteritis surveillance at sentinel site laboratory and rotavirus positive specimens were further genotyped at Regional Reference Laboratory by RT-PCR.ResultsDiarrhea hospitalizations decreased after rotavirus vaccine introduction. The median proportion of annual hospitalizations due to diarrhea was 26% (range: 31–22%) before vaccine introduction; the proportion was 25% the year of vaccine introduction, 17% in 2015 and 16% in 2016. Rotavirus positivity paralleled patterns observed in diarrhea. Before vaccine introduction, 56% of stool specimens tested positive for rotavirus; the percent positive was 13% in 2015, 12% in 2016. Diverse genotypes were detected in the pre-vaccine period; the most common were G3P[8] (n = 53; 66%), G2P[4] (n = 12; 15%), and G1P[8] (n = 11; 14%). 6 distinct genotypes were found in 2015; the most common genotype was G2P[4] (n = 10; 67%), the remaining, 5, G12[P8], G3[P8], G1G3[P4], G3G12[P4][P8] and G1G3[NT] had one positive specimen each.ConclusionsFollowing rotavirus vaccine introduction all-cause diarrhea and rotavirus-specific hospitalizations declined dramatically. The most common genotypes detected in the pre-vaccine period were G3P[8] and G2P[4] in 2015, the post vaccine period.     

Impact of maternal and pre-existing antibodies on immunogenicity of inactivated rotavirus vaccines

Rotavirus (RV) is a major pathogen causing severe diarrhea in infants and children aged less than 5 years. Vaccination is an economically feasible and effective strategy to prevent rotavirus infections. However, immune efficacy of live vaccines could be interfered by maternal antibodies and pre-existing antibodies of children. To develop an inactivated rotavirus vaccine (IRV), we had previously isolated a wild-type human rotavirus strain ZTR-68-A (G1P[8]) from the fecal samples of infants having severe diarrhea in a region endemic for the presence of this pathogen. In our present study, we assessed whether the presence of maternal and pre-existing antibodies in newborn BALB/c mice affected the immunogenicity of IRV administered to these animals. Our results indicate that maternal antibodies, generated from either vaccine immunization or rotavirus infection, showed partial influence with the immune responses generated by two doses of IRV vaccination. Increasing the number of immunizations can significantly improve the titer of serum neutralizing antibody and a seroconversion rate of up to 100%. In newborn mice, single-virus infection did not elicit detectable levels of serum neutralizing antibodies. After an IRV vaccination, the immune responses of these mice remained unaffected, with no significant differences in titers compared with those of control-group mice. In summary, choosing a suitable immunization dose and dosing frequency is essential for the immune effectiveness of IRV. The results of this study will provide animal experimental support for the IRV clinical research in future.     

Impact of routine rotavirus vaccination on all-cause and rotavirus hospitalizations during the first four years following vaccine introduction in Rwanda

BackgroundRwanda introduced pentavalent rotavirus vaccine into its national immunization program in 2012. To determine the long-term impact of rotavirus vaccine on disease burden in a high burden setting, we examined trends in rotavirus and all-cause diarrhea hospitalizations in the first four years following rotavirus vaccine introduction.MethodsWe used data from an active surveillance system, from a review of pediatric ward registries, and from the Health Management Information System to describe trends in rotavirus and all-cause diarrhea hospitalizations from January 2009 through December 2016. Percent reductions were calculated to compare the number of all-cause and rotavirus diarrhea hospitalizations pre- and post-rotavirus vaccine introduction.ResultsThe proportion of diarrhea hospitalizations due to rotavirus declined by 25–44% among all children <5 years of age during 2013–2015 with a shift in rotavirus hospitalizations to older age groups. The proportion of total hospitalizations due to diarrhea among children <5 years of age decreased from 19% pre-vaccine introduction to 12–13% post-vaccine introduction. In the national hospital discharge data, substantial decreases were observed in all-cause diarrhea hospitalizations among children <5 years of age in 2013 and 2014 but these gains lessened in 2015–2016.DiscussionContinued monitoring of long-term trends in all-cause diarrhea and rotavirus hospitalizations is important to ensure that the impact of the vaccination program is sustained over time and to better understand the changing age dynamics of diarrhea and rotavirus hospitalizations in the post-vaccine introduction era.     

Impact of rotavirus vaccination on rotavirus hospitalizations in Taiwanese children

In 2006, two rotavirus vaccines were licensed in Taiwan but were not added to the national immunization schedule. National Health Insurance data from 2003 through 2017 were used to compare rotavirus-associated pediatric hospitalizations before and after vaccine introduction. Rotavirus hospitalization rates among children < 5 years of age significantly declined by 24% (95% confidence interval [CI] 23 – 25%) in post-vaccine compared to pre-vaccine rotavirus seasons. Rotavirus hospitalization rates declined by 42% (95% CI 39 – 44%) among infants < 12 months of age, and by 38% (95% CI 36 – 40%) among children 12 – 23 months of age. These findings suggest that, despite not being included in the national immunization schedule, rotavirus vaccines had a measurable impact on reducing rotavirus hospitalization burden among Taiwanese children.     

Potential epidemiological and economical impact of two rotavirus vaccines in Colombia

A complete economic study was carried out to assess the economical impact of two rotavirus vaccine in Colombia. A Markov decision model was built to assess the health outcomes from birth to 24 months of age for three hypothetical cohorts: one unvaccinated, one vaccinated with 2 doses of Rotarix™ and the third, with 3 doses of Rotateq™. Without vaccination, the annual number of medical visits by diarrhea in children under 2 years would be 1,293,159 cases, with 105,378 medical visits and 470 deaths (IC95% 295–560) related to rotavirus. Without vaccination, rotavirus disease would cost around USD$8 millions including direct and indirect costs. Assuming a cost per dose of USD$7.5, average cost-effectiveness ratio would be USD$663/DALY with Rotarix and USD$1391 with Rotateq. When price per dose falls below USD$7 both vaccines yield a similar average cost-effectiveness ratio (USD$1063/DALY). Incremental cost-effectiveness ratio of Rotateq versus Rotarix was USD$7787/DALY. Cost-effectiveness ratio was influenced mainly by vaccine cost and cost per case hospitalized. Other programmatic aspects such as number of doses to be applied, likelihood of completing vaccination schedule with shorter versus longer schedules, and storage space within the chain cold should be considered to make decisions on which vaccine should be introduced. In conclusion, vaccinating against rotavirus in Colombia with either vaccine would be very cost effective. If cost per vaccinated children falls below USD$3 per dose vaccination would be cost saving.     

Predictors of oral rotavirus vaccine immunogenicity in rural Zimbabwean infants

BackgroundOral rotavirus vaccines (RVV) have poor immunogenicity in low-income countries, for reasons that remain unclear. This study identified the determinants of RVV immunogenicity among infants in rural Zimbabwe.MethodsAnti-rotavirus IgA titres were measured among a sub-group of infants enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial (NCT01824940). SHINE was a cluster-randomized trial of improved infant and young child feeding, and improved water, sanitation and hygiene (WASH) in two rural Zimbabwean districts. Infants received RVV as part of the national immunisation programme. Among HIV-unexposed infants in the non-WASH trial arms, we evaluated associations between potential risk factors (vaccine schedule and dose, maternal and infant nutritional status, infant diarrhoea, and household environment) and RVV immunogenicity (seroconversion, seropositivity and geometric mean titres) using multivariable regression.ResultsAmong 219 infants with seroconversion data, 43 (20%) successfully seroconverted and 176 (80%) failed to seroconvert to RVV. Seroconversion was positively associated with a higher length-for-age Z-score (LAZ) around the time of vaccination (adjusted RR 1.27 (95% CI 1.04, 1.55), P = 0.021), and negatively associated with concurrent OPV and RVV administration (adjusted RR 0.36 (0.19, 0.71), P = 0.003). Among 472 infants with post-vaccination titres, a higher LAZ score was associated with increased seropositivity (aRR 1.21 (95% CI 1.06, 1.38), P = 0.004), and higher birthweight was associated with increased IgA titres (0.45 (95%CI 0.18, 1.09) U/mL greater per 100 g gain in birthweight; P = 0.001).ConclusionsInfant ponderal and linear growth were positively associated with RVV immunogenicity, while concurrent administration of OPV was negatively associated with RVV immunogenicity. Together, these findings suggest that improving foetal growth and separating RVV and OPV administration are plausible approaches to increasing RVV immunogenicity.     

Safety and immunogenicity of live attenuated quadrivalent human-bovine (UK) reassortant rotavirus vaccine administered with childhood vaccines to infants

The safety and immunogenicity of an orally administered, live rotavirus vaccine comprised of four strains, each with a titer of 10^5.3 or 10^5.8 pfu, and each having 10 genes from the UK bovine strain and the VP7 gene from human rotavirus serotype 1, 2, 3, or 4, were evaluated in adults, young children and infants in randomized, double-blind phase 1 trials. Three doses of rotavirus vaccine or placebo given with childhood immunizations to infants at 2, 4, and 6 months of age were well tolerated and did not inhibit antibody responses to childhood vaccines which included DTP, Hib, hepatitis B and OPV. Serum rotavirus antibody responses were detected in 12 of 20 infants after 1 dose, and in 19/19 of the vaccinees after three doses. Neutralizing antibody responses were detected more often against the bovine rotavirus UK strain (95%) than to human rotavirus VP7 serotypes 1 (37%), 2 (32%), 3 (32%) or 4 (32%). The efficacy of this quadrivalent rotavirus vaccine needs to be evaluated further.     

Economic analysis for national immunization program planning: A case of rotavirus vaccines in Burundi

BackgroundIn Burundi, diarrhea is the third leading cause of mortality among children under five years of age. This study conducted an economic analysis of rotavirus vaccination program in Burundi.MethodsA Markov model was constructed to simulate clinical and economic outcomes for the 2019 birth cohort for a period of 5 years. Empirical costing data were collected. ICER per episode averted, ICER per death averted, ICER per DALY averted, net present value, and budget impact were estimated for 4 brands of WHO pre-qualified rotavirus vaccines. One-way and probabilistic sensitivity analysis as well as threshold analysis were performed.ResultsFor the base case, while all four WHO pre-qualified rotavirus vaccines were cost-effective (ICER < 3 GDP per capita), three of them (i.e. Rotarix, Rotavac and Rotasiil) were very cost-effective (ICER <1 GDP per capita) from both the provider and societal perspectives. The vaccines were still very cost-effective at a price increase of up to US$ 5.09, US$ 3.16, US$ 3.89, and US$ 2.69 for Rotarix, RotaTeq, Rotavac, and Rotasiil, respectively. Probabilistic sensitivity analysis indicated that vaccination programs with Rotarix, RotaTeq, Rotavac, and Rotasiil are cost-effective at a probability of 93.8%, 27%, 99.1%, and 92.7%, respectively. All vaccination programs were cost-beneficial with a net present value in the range of US$ 5,214,912 and US$ 11,135,997.The budget required to run the vaccination program, estimated with break-even prices, ranged between US$ 42,249,498 and US$ 53,487,935 for a 5-year time period. When compared to the GDP of Burundi in 2019, these are are less than 2%.ConclusionThe rotavirus vaccine is good value for money. Findings from this study offer evidence on potential economic benefits as well as the required budget for different rotavirus vaccination programs, which could be useful for future planning related to rotavirus vaccine coverage in Burundi after graduation from GAVI.     

The efficacy and safety of rotavirus vaccines in countries in Africa and Asia with high child mortality

Rotavirus remains a leading cause of diarrhoeal morbidity and mortality in young children and rotavirus vaccines are critical for reducing global disease burden. This report addresses the performance of rotavirus vaccines in countries with high child mortality. We performed a sensitivity analysis as part of a systematic review on rotavirus vaccines to inform development of World Health Organization vaccine recommendations. The efficacy of four prequalified vaccines against severe rotavirus gastroenteritis was similar across high mortality settings in Asia and Africa. Within the first year following vaccination, vaccine efficacy for the four vaccines ranged from 48% to 57% while in the second year, efficacy ranged from 29% to 54%. The four vaccines showed no increase in intussusception risk in these settings. All four vaccines appear to prevent significant numbers of severe rotavirus gastroenteritis episodes with no measurable increase in intussusception risk in high mortality settings in Africa and Asia.     

Evidence of the impact of monovalent rotavirus vaccine on childhood acute gastroenteritis hospitalization in Togo

BackgroundMonovalent rotavirus vaccine (RV1) was introduced in the immunization schedule of Togo in June 2014. We evaluated the impact of rotavirus vaccines on acute gastroenteritis (AGE) and rotavirus-associated hospitalizations in Togolese children.MethodsSentinel surveillance for AGE (defined as ≥3 liquid or semi-liquid stools/24 h lasting <7 days) hospitalizations among children <5 years of age was conducted in two sites in the capital city, Lome. ELISA was used for diagnosis of rotavirus infection in children with AGE. Additionally, review of hospitalization registers was performed at five hospitals to assess trends in AGE hospitalizations among children aged <5 years. For the vaccine impact assessment, pre-rotavirus vaccine introduction (July 2010-June 2014) and post-rotavirus vaccine introduction (July 2014-June 2016) periods were compared for annual changes in proportions of hospitalizations associated with AGE and rotavirus.ResultsDuring the pre-vaccine period, sentinel surveillance showed that 1017 patients were enrolled and 57% (range, 53–62%) tested positive for rotavirus, declining to 42% (23% reduction) in the first post-vaccine year and to 26% (53% reduction) in the second post-vaccine year; declines were most marked among infants. The patient register review showed that, compared with pre-vaccine rotavirus seasons, declines in hospitalizations due to all-cause AGE during post-vaccine rotavirus seasons were 48% among <1 year age-group in both first and second years following vaccine introduction. Among 1–4 year olds no reduction was noted in the first year and a 19% decline occurred in the second year.ConclusionsWe report rapid and marked reduction in the number of AGE hospitalizations and the proportion of AGE hospitalizations attributable to rotavirus in the first two years post- RV1 implementation in Togo. It is necessary to monitor long-term vaccine impact on rotavirus disease burden through continued surveillance.     

Cost-effectiveness of rotavirus vaccination in children under five years of age in 195 countries: A meta-regression analysis

BackgroundRotavirus caused an estimated 151,714 deaths from diarrhea among children under 5 in 2019. To reduce mortality, countries are considering adding rotavirus vaccination to their routine immunization program. Cost-effectiveness analyses (CEAs) to inform these decisions are not available in every setting, and where they are, results are sensitive to modeling assumptions, especially about vaccine efficacy. We used advances in meta-regression methods and estimates of vaccine efficacy by location to estimate incremental cost-effectiveness ratios (ICERs) for rotavirus vaccination in 195 countries.MethodsBeginning with Tufts University CEA and Global Health CEA registries we used 515 ICERs from 68 articles published through 2017, extracted 938 additional one-way sensitivity analyses, and excluded 33 ICERs for a sample of 1,418. We used a five-stage, mixed-effects, Bayesian metaregression framework to predict ICERs, and logistic regression model to predict the probability that the vaccine was cost-saving. For both models, covariates were vaccine characteristics including efficacy, study methods, and country-specific rotavirus disability-adjusted life-years (DALYs) and gross domestic product (GDP) per capita. All results are reported in 2017 United States dollars.ResultsVaccine efficacy, vaccine cost, GDP per capita and rotavirus DALYs were important drivers of variability in ICERs. Globally, the median ICER was $2,289 (95% uncertainty interval (UI): $147–$38,993) and ranged from $85 per DALY averted (95% UI: $13–$302) in Central African Republic to $70,599 per DALY averted (95% UI: $11,030–$263,858) in the United States. Among countries eligible for support from Gavi, The Vaccine Alliance, the mean ICER was $255 per DALY averted (95% UI: $39–$918), and among countries eligible for the PAHO revolving fund, the mean ICER was $2,464 per DALY averted (95% UI: $382–$3,118).ConclusionOur findings incorporate recent evidence that vaccine efficacy differs across locations, and support expansion of rotavirus vaccination programs, particularly in countries eligible for support from Gavi, The Vaccine Alliance.     

Re-evaluating the cost and cost-effectiveness of rotavirus vaccination in Bangladesh,Ghana, and Malawi: A comparison of three rotavirus vaccines

IntroductionDiarrhea is a leading cause of mortality worldwide and rotavirus accounts for many of these deaths. As of August 2018, 96 countries have introduced rotavirus vaccines into their immunization programs. Two rotavirus vaccines, Rotarix® and RotaTeq®, have been WHO-prequalified since 2009, with Rotarix® being the preferred product of most Gavi-supported countries. ROTAVAC® and ROTASIIL® have both been prequalified recently.Materials and methodsWe reevaluated the costs and cost-effectiveness of rotavirus vaccination in Bangladesh, Ghana, and Malawi and compared Rotarix®, ROTAVAC®, and ROTASIIL® in each country. For consistency with previously published analyses in these countries, we used the same Excel-based cohort model and much of the same data as the original analyses. We varied the expected price (with and without Gavi subsidy), wastage, and incremental health system costs associated with each vaccine. We assumed the same efficacy and waning assumptions following administration of two or three doses for the respective product.ResultsThe discounted cost per DALY averted compared to no vaccination ranged from 0.3 to 1.3 times GNI per capita for each vaccine. With the Gavi subsidy, the average cost-effectiveness ratios were below 0.3 times GNI per capita in all three countries. Though critical empirical cost data are not yet available, Rotarix® is the least costly and most cost-effective product in the countries examined in this modelling study. However, small decreases in the incremental health system cost for other products could result in cost and cost-effectiveness outcomes that match or surpass those of Rotarix®.ConclusionCountries may wish to consider new rotavirus vaccines entering the market. Countries should carefully examine multiple product attributes including price and the incremental health system costs associated with each vaccine. These costs will vary by country and may be a defining factor in determining the least costly and most cost-effective product for the population.     

The effect of rotavirus immunization on rotavirus gastroenteritis hospitalization rates in military dependents

We conducted a retrospective review of all U.S. military dependents less than 5 years old hospitalized with rotavirus-associated gastroenteritis from July 2003 to June 2009. The two post-vaccine seasons showed a significant reduction of 62.4% (95% CI, 58.6-65.8, P < 0.001) in rotavirus gastroenteritis hospitalization rate compared to the three pre-vaccine seasons. Infants less than 12 months old showed the greatest reduction in incidence at 75.3%. A substantial decrease was also seen in unvaccinated children as well. Vaccine efficacy against hospitalization was 86.0% (95% CI, 77.7-91.3) after just a single dose. The overwhelming majority of children hospitalized for rotavirus since the introduction of the vaccine (ranging from 91.8 to 100% per season) had not received any of the rotavirus vaccine series.     

Cost-effectiveness of rotavirus vaccination programs in Taiwan

Background

In Taiwan, two rotavirus vaccines are available on the private market, but are not included in the National Immunization Program (NIP). To help assess whether to include rotavirus vaccines in the NIP, we examined the potential impact and cost-effectiveness of vaccination, from the health care system perspective alone.

Methods

We used a Microsoft Excel-based model to assess rotavirus vaccination impact on rotavirus disease burden and the cost-effectiveness of 2-dose and 3-dose vaccination programs among a birth cohort of Taiwanese children followed for 5 years. Principal model inputs included data on rotavirus disease burden and related healthcare costs, vaccination cost and coverage rates, and vaccine efficacy. Principal model outputs included the number of health-related events and costs averted and incremental cost per disability-adjusted life year averted.

Results

A national rotavirus vaccination program, regardless of number of doses per course, would prevent 4 deaths, >10,500 hospitalizations, and >64,000 outpatient visits due to rotavirus infection among children <5 years annually, resulting in ∼80%, 90%, and 70% declines in these outcomes, respectively, and a ∼$7 million decline in annual medical costs. A national 2- or 3-dose vaccination program would be cost-saving up to $13.30/dose ($26.60/course) or $7.98/dose ($23.94/course), respectively; very cost-effective up to $24.08 per dose ($48.16/course) or $15.18/dose ($45.54/course), respectively; and cost-effective up to $45.65/dose ($91.30/course) or $29.59/dose ($88.77/course), respectively.

Conclusions

A national rotavirus vaccination program could substantially reduce rotavirus disease burden among Taiwanese children and be potentially cost-effective, depending on the vaccine price.     

Reaching every child with rotavirus vaccine: Report from the 10th African rotavirus symposium held in Bamako,Mali

The Center for Vaccine Development – Mali (CVD – Mali), the World Health Organization’s regional office in Africa (WHO/AFRO), and the CVD at the University of Maryland School of Medicine hosted the 10th African Rotavirus Symposium in Bamako, Mali on 1–2 June 2016. The symposium is coordinated by WHO/AFRO, the Regional Rotavirus Reference Laboratories, and the African Rotavirus Network (ARN), with support from the Bill & Melinda Gates Foundation. The event brings together leading rotavirus researchers, scientists, and policy-makers from across Africa and the world. Over 150 participants, from 31 countries, including 27 in Africa, joined forces to address the theme “Reaching Every Child in Africa with Rotavirus Vaccines.” This symposium, the first in francophone Africa, occurred at an unprecedented time when 33 African countries had introduced rotavirus vaccines into their national immunization programs. The symposium concluded with a Call to Action to introduce rotavirus vaccines in the 21 remaining African countries, to increase access in countries with existing vaccination programs, and to continue surveillance and research on rotavirus and other diarrheal diseases.     

A decade of rotavirus vaccination in Africa - Saving lives and changing the face of diarrhoeal diseases: Report of the 12th African Rotavirus Symposium

The African Rotavirus Network organised the 12^th African Rotavirus Symposium (ARS) from 30 July to 1 August 2019 in Johannesburg, South Africa. The symposium theme “A decade of rotavirus vaccination in Africa - Saving lives and changing the face of diarrhoeal diseases”, included sessions aimed at sharing ideas and expertise on prevention and control of diarrhoeal disease in Africa. Inter alia, the delegates reviewed global and regional epidemiological trends on rotavirus diarrhoea, progress and experiences on rotavirus vaccine introduction, including vaccine safety monitoring and impact in Africa, scientific advances in developing newer rotavirus vaccines, surveillance and research on other diarrhoeal pathogens, and providing an enabling environment for networking. Importantly, the 12^th ARS served to commemorate the 20^th anniversary of the African Rotavirus Network (AfrRN) coinciding with the 50th anniversary of the South African Medical Research Council.Four oral, live-attenuated rotavirus vaccines are currently prequalified by the WHO (Rotarix, RotaTeq, Rotavac and RotaSiil). African countries utilising rotavirus vaccines in routine national immunisation programmes are realising their effectiveness and impact on diarrhoeal disease morbidity. An ~40% reduction in hospitalisations of <5-year-olds with acute gastroenteritis following rotavirus vaccine introduction, was reported between 2006 and 2018 in 92,000 children from the WHO-coordinated African Rotavirus Surveillance Network (AfrRSN) comprising 33 Member States. This was corroborated by a meta-analysis of published data, sourced from January 2000 to August 2018 that reported substantial reductions in rotavirus hospitalisations in countries using rotavirus vaccines. However, it was highlighted that the transition of some countries from Gavi-eligibility and vaccine supply shortfalls present significant challenges to achieving the full impact of rotavirus immunization in Africa. The wide diversity of rotavirus genotypes continues in Africa, with variation observed both geographically and temporally. There is currently no evidence to suggest that the emergence of rotavirus strains not included in the current vaccines do escape vaccine-induced immunity.     

Effects of rotavirus NSP4 protein on the immune response and protection of the SR69A-VP8* nanoparticle rotavirus vaccine

Rotavirus causes severe diarrhea and dehydration in young children. Even with the implementation of the current live vaccines, rotavirus infections still cause significant mortality and morbidity, indicating a need for new rotavirus vaccines with improved efficacy. To this end, we have developed an S_R69A-VP8*/S₆₀-VP8* nanoparticle rotavirus vaccine candidate that will be delivered parenterally with Alum adjuvant. In this study, as parts of our further development of this nanoparticle vaccine, we evaluated 1) roles of rotavirus nonstructural protein 4 (NSP4) that is the rotavirus enterotoxin, a possible vaccine target, and an immune stimulator, and 2) effects of CpG adjuvant that is a toll-like receptor 9 (TLR9) ligand and agonist on the immune response and protection of our S_R69A-VP8*/S₆₀-VP8* nanoparticle vaccine. The resulted vaccine candidates were examined for their IgG responses in mice. In addition, the resulted mouse sera were assessed for i) blocking titers against interactions of rotavirus VP8* proteins with their glycan ligands, ii) neutralization titers against rotavirus replication in cell culture, and iii) passive protection against rotavirus challenge with diarrhea in suckling mice. Our data showed that the Alum adjuvant appeared to work better with the S_R69A-VP8*/S₆₀-VP8* nanoparticles than the CpG adjuvant, while an addition of the NSP4 antigen to the S_R69A-VP8*/S₆₀-VP8* vaccine may not help to further increase the immune response and protection of the resulted vaccine.