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.     

Impact of rotavirus vaccines in Sub-Saharan African countries

By the end of 2017, 32 (68%) of 47 countries in the World Health Organization’s African Region had introduced rotavirus vaccine into their national immunization programs, including 27 countries that received financial support from the Gavi, the Vaccine Alliance. Several early introducing African countries previously evaluated the impact, vaccine effectiveness, and/or cost effectiveness of their routine rotavirus vaccination programs and found that rotavirus vaccine was effective and resulted in substantial declines in hospitalizations due to rotavirus. This Special Issue of Vaccine provides additional rotavirus vaccine effectiveness and impact data from a broader range of African countries, describes the longer term impact and potential indirect benefits of rotavirus vaccination programs, describes trends in circulating genotypes in the pre- and post-vaccine introduction eras, and evaluates the cost-effectiveness of a rotavirus vaccination program in a post-introduction setting. As countries begin transitioning from Gavi support, the findings of these studies provide evidence of the impact and effectiveness of rotavirus vaccination programs under conditions of routine use.     

Interference of oral poliovirus vaccine on RIT 4237 oral rotavirus vaccine

A vaccination trial, performed on 86 3-month-old infants, has shown that the ability of the RIT 4237 live attenuated rotavirus strain to induce seroconversion is dramatically reduced when administered with live poliovirus vaccine. In a subsequent trial performed on 93 infants the attempt to overcome the poliovirus interference by administering two doses of associated vaccines was unsuccessful. No interference by the RIT 4237 strain on live attenuated polioviruses was observed.     

Immunogenicity, reactogenicity and safety of the human rotavirus vaccine RIX4414 oral suspension (liquid formulation) in Finnish infants

The lyophilized formulation of a human rotavirus vaccine, Rotarix™ (RIX4414) is highly immunogenic. In order to comply with the World Health Organization's (WHO) recommendation, a liquid formulation of the vaccine that does not require reconstitution was developed. The immunogenicity, reactogenicity and safety of the liquid formulation were compared with lyophilized formulation in two Finnish studies.In Study A infants aged 6-12 weeks received two doses of the lyophilized or liquid formulation of the vaccine or placebo following a 0,1 month schedule. In Study B, infants aged 10-17 weeks received two doses of either liquid or lyophilized formulation of the vaccine. In both studies, anti-rotavirus IgA antibodies were assessed pre-vaccination and one month post-Dose 2. In Study A, the anti-rotavirus seroconversion rate was 90% (95% CI: 81.2-95.6%) and 83.7% (95% CI: 74.2-90.8%) in the groups that received the liquid and the lyophilized formulation of RIX4414, respectively; the respective anti-rotavirus IgA seroconversion rates in Study B were 88.6% (95% CI: 86.1-90.8%) and 90.5% (95% CI: 86.2-93.8%). Reactogenicity and safety profiles of the two vaccine formulations were similar.Liquid formulation of the rotavirus vaccine allows greater flexibility in supply and reduces logistical costs.     

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.     

Low fecal rotavirus vaccine virus shedding is significantly associated with non-secretor histo-blood group antigen phenotype among infants in northern Pretoria,South Africa

Histo-blood group antigens are recognized by rotaviruses in a P- genotype dependent manner and their frequency in a population can influence fecal virus shedding. This study investigated the rate of fecal shedding of Rotarix vaccine and its association with HBGA phenotype distribution in South Africa. Stool and saliva specimens were collected from 150 infants attending immunization on the day of both first and second doses and 7 days later. Virus shedding was detected by real-time qPCR while HBGA phenotypes in saliva were determined by enzyme linked immunosorbent assay. Vaccine virus shedding was higher (23.6%) after the first dose than the second dose (4.7%). About 77% of virus-shedding infants were secretors (OR = 129; 95% CI, 6.088 – 2733), compared with none of non-virus shedding infants. Non-secretor status was significantly associated with low vaccine virus shedding while the likelihood of shedding was significantly higher in secretors.     

Impact of enterovirus and other enteric pathogens on oral polio and rotavirus vaccine performance in Bangladeshi infants

BackgroundOral polio vaccine (OPV) and rotavirus vaccine (RV) exhibit poorer performance in low-income settings compared to high-income settings. Prior studies have suggested an inhibitory effect of concurrent non-polio enterovirus (NPEV) infection, but the impact of other enteric infections has not been comprehensively evaluated.MethodsIn urban Bangladesh, we tested stools for a broad range of enteric viruses, bacteria, parasites, and fungi by quantitative PCR from infants at weeks 6 and 10 of life, coincident with the first OPV and RV administration respectively, and examined the association between enteropathogen quantity and subsequent OPV serum neutralizing titers, serum rotavirus IgA, and rotavirus diarrhea.ResultsCampylobacter and enterovirus (EV) quantity at the time of administration of the first dose of OPV was associated with lower OPV1-2 serum neutralizing titers, while enterovirus quantity was also associated with diminished rotavirus IgA (−0.08 change in log titer per tenfold increase in quantity; P = 0.037), failure to seroconvert (OR 0.78, 95% CI: 0.64–0.96; P = 0.022), and breakthrough rotavirus diarrhea (OR 1.34, 95% CI: 1.05–1.71; P = 0.020) after adjusting for potential confounders. These associations were not observed for Sabin strain poliovirus quantity.ConclusionIn this broad survey of enteropathogens and oral vaccine performance we find a particular association between EV carriage, particularly NPEV, and OPV immunogenicity and RV protection. Strategies to reduce EV infections may improve oral vaccine responses.ClinicalTrials.gov Identifier: NCT01375647.     

The fecal microbiome and rotavirus vaccine immunogenicity in rural Zimbabwean infants

BackgroundOral rotavirus vaccine (RVV) immunogenicity is considerably lower in low- versus high-income populations; however, the mechanisms underlying this remain unclear. Previous evidence suggests that the gut microbiota may contribute to differences in oral vaccine efficacy.MethodsWe performed whole metagenome shotgun sequencing on stool samples and measured anti-rotavirus immunoglobulin A in plasma samples from a subset of infants enrolled in a cluster randomized 2 × 2 factorial trial of improved water, sanitation and hygiene and infant feeding in rural Zimbabwe (SHINE trial: NCT01824940). We examined taxonomic microbiome composition and functional metagenome features using random forest models, differential abundance testing and regression analyses to explored associations with RVV immunogenicity.ResultsAmong 158 infants with stool samples and anti-rotavirus IgA titres, 34 were RVV seroconverters. The median age at stool collection was 43 days (IQR: 35–68), corresponding to a median of 4 days before the first RVV dose. The infant microbiome was dominated by Bifidobacterium longum. The gut microbiome differed significantly between early (≤42 days) and later samples (>42 days) however, we observed no meaningful differences in alpha diversity, beta diversity, species composition or functional metagenomic features by RVV seroconversion status. Bacteroides thetaiotaomicron was the only species associated with anti-rotavirus IgA titre. Random forest models poorly classified seroconversion status by both composition and functional microbiome variables.ConclusionsRVV immunogenicity is low in this rural Zimbabwean setting, however it was not associated with the composition or function of the early-life gut microbiome in this study. Further research is warranted to examine the mechanisms of poor oral RVV efficacy in low-income countries.     

A multinational,randomized, placebo-controlled trial to assess the immunogenicity,safety, and tolerability of live attenuated influenza vaccine coadministered with oral poliovirus vaccine in healthy young children

Live attenuated influenza vaccine (LAIV) provides a useful tool to rapidly immunize populations in the developing world to prevent influenza outbreaks. In this noninferiority trial conducted in Asia and South America, where oral poliovirus vaccine (OPV) is still used, 2503 children aged 6 to <36 months with three polio immunizations were randomized to receive LAIV + OPV, placebo + OPV, or LAIV only. Immune responses in children receiving concomitant LAIV + OPV were noninferior to those observed in recipients of either vaccine alone. Response rates for different poliovirus types were similar in recipients of LAIV + OPV and placebo + OPV. Response rates to all influenza strains were similar in LAIV + OPV and LAIV-only recipients. Concomitant OPV and LAIV were safely administered to young children.     

Development and introduction of inactivated poliovirus vaccines derived from Sabin strains in Japan

During the endgame of global polio eradication, the universal introduction of inactivated poliovirus vaccines is urgently required to reduce the risk of vaccine-associated paralytic poliomyelitis and polio outbreaks due to wild and vaccine-derived polioviruses. In particular, the development of inactivated poliovirus vaccines (IPVs) derived from the attenuated Sabin strains is considered to be a highly favorable option for the production of novel IPV that reduce the risk of facility-acquired transmission of poliovirus to the communities. In Japan, Sabin-derived IPVs (sIPVs) have been developed and introduced for routine immunization in November 2012. They are the first licensed sIPVs in the world. Consequently, trivalent oral poliovirus vaccine was used for polio control in Japan for more than half a century but has now been removed from the list of vaccines licensed for routine immunization. This paper reviews the development, introduction, characterization, and global status of IPV derived from attenuated Sabin strains.     

Immunogenicity of four doses of oral poliovirus vaccine when co-administered with the human neonatal rotavirus vaccine (RV3-BB)

BackgroundThe RV3-BB human neonatal rotavirus vaccine was developed to provide protection from severe rotavirus disease from birth. The aim of this study was to investigate the potential for mutual interference in the immunogenicity of oral polio vaccine (OPV) and RV3-BB.MethodsA randomized, placebo-controlled trial involving 1649 participants was conducted from January 2013 to July 2016 in Central Java and Yogyakarta, Indonesia. Participants received three doses of oral RV3-BB, with the first dose given at 0–5 days (neonatal schedule) or ~8 weeks (infant schedule), or placebo. Two sub-studies assessed the immunogenicity of RV3-BB when co-administered with either trivalent OPV (OPV group, n = 282) or inactivated polio vaccine (IPV group, n = 333). Serum samples were tested for antibodies to poliovirus strains 1, 2 and 3 by neutralization assays following doses 1 and 4 of OPV.ResultsSero-protective rates to poliovirus type 1, 2 or 3 were similar (range 0.96–1.00) after four doses of OPV co-administered with RV3-BB compared with placebo. Serum IgA responses to RV3-BB were similar when co-administered with either OPV or IPV (difference in proportions OPV vs IPV: sIgA responses; neonatal schedule 0.01, 95% CI −0.12 to 0.14; p = 0.847; infant schedule −0.10, 95% CI −0.21 to −0.001; p = 0.046: sIgA GMT ratio: neonatal schedule 1.23, 95% CI 0.71–2.14, p = 0.463 or infant schedule 1.20, 95% CI 0.74–1.96, p = 0.448).ConclusionsThe co-administration of OPV with RV3-BB rotavirus vaccine in a birth dose strategy did not reduce the immunogenicity of either vaccine. These findings support the use of a neonatal RV3-BB vaccine where either OPV or IPV is used in the routine vaccination schedule.     

Safety and immunogenicity of RIX4414 live attenuated human rotavirus vaccine in adults, toddlers and previously uninfected infants

A live attenuated human rotavirus (HRV) vaccine, strain RIX4414, was tested sequentially in adults, previously infected toddlers, and previously uninfected infants. A single dose was given to adults and toddlers and found well tolerated. Next, a dose ranging (three different viral concentrations) safety and immunogenicity study was conducted in rotavirus IgA antibody negative infants (N= 192), who received two doses of RIX4414 vaccine or placebo at 2 and 4 months of age. No side effects were seen after vaccination. Specifically, administration of RIX4414 vaccine was not temporally associated with fever, diarrhea, or increase in liver transaminases. Rotavirus IgA seroconversion ranged from 50 to 88% after one dose and from 73 to 96% after two doses, depending on vaccine titer. After the first dose, on days 7-9 post vaccination, between 38 and 60% of the infants shed the vaccine virus, whereas after the second dose only 0 to 13% of the vaccinees shed the vaccine virus. It is concluded that RIX4414 strain HRV vaccine is virtually non-reactogenic and, at high titer, highly immunogenic in susceptible infants.     

Cost-effectiveness of infant vaccination with RIX4414 (Rotarix™) in the UK

This study estimated the cost-effectiveness of infant rotavirus vaccination with Rotarix™ in the UK, taking into account community rotavirus infections that do not present to the healthcare system. A Markov model compared the costs and outcomes of vaccination versus no vaccination in a hypothetical birth cohort of children followed over a lifetime, from a societal perspective and the perspective of the National Health Service (NHS). The model estimated costs and quality-adjusted life-years (QALYs) lost due to death, hospitalisation, general practitioner (GP) consultation, emergency attendance and calls to NHS Direct for rotavirus infection in children aged <5 years. Time lost from work and parents’ travel costs were also included in the societal perspective. The base case cost-effectiveness ratio for vaccination compared with no vaccination was £23,298/QALY from the NHS perspective and £11,459 from the societal perspective. In sensitivity analysis, the most important parameters were hospitalisation cost and number of GP consultations. Addition of Rotarix™ to the paediatric vaccination schedule would be a cost-effective policy option in the UK at the threshold range (£20,000–30,000/QALY) currently adopted by the National Institute for Health and Clinical Excellence.     

Shedding of oral pentavalent bovine-human reassortant rotavirus vaccine indicates high uptake rate of vaccine and prominence of G-type G1

BackgroundLive oral pentavalent bovine-human reassortant rotavirus (RV) vaccine, RotaTeq®, contains bovine rotaviruses reassorted with human G-types G1, G2, G3 and G4, and P-type P[8]. Shedding of RotaTeq® vaccine, as studied by RT-PCR, has been shown to be more common than initially reported, and may include formation of vaccine-derived double-reassortant G1P[8] RVs. We studied the extent and duration of RotaTeq® vaccine virus shedding, genotypes shed, and clinical symptoms associated with shedding.Material and methodsWe enrolled a total of 301 infants who received RotaTeq® vaccine according to Finnish schedule at 2, 3 and 5 months of age. Stool samples were collected 5–10 days after the first and 0–7 days before the third dose of the vaccine. Additional stool samples 6 and 12 weeks later were collected if the second stool sample was positive. All stools were studied with RT-PCR for RV VP7, VP4 and VP6. Parents filled a symptom diary for a week after each vaccine dose.ResultsWe found that 93% of the vaccinees shed vaccine related viral particles in one sample taken 5–10 days after the first dose, indicating that stool shedding is very common and may be regarded as a marker of successful vaccination. Genotype G1 was the predominant genotype in shedding, often in association with P[8], and the only genotype found in long-term shedding. Also G4 was commonly detected whereas other vaccine G-types and bovine-type P[5] were not.ConclusionsShedding of RotaTeq® vaccine-derived viruses is a sign for successful vaccination. Intense shedding of G1 with or without P[8]reflects effective multiplication and may be an important factor in the induction of protective immunity. Shedding of G1 containing vaccine viruses may be prolonged up to 8 months of age. These results suggest that the pentavalent vaccine functions largely like a monovalent G1 vaccine.Eudra-CT: 2014-004252-60.     

Efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RV5) in healthy Chinese infants: A randomized,double-blind,placebo-controlled trial

BackgroundA randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RotaTeq™, RV5) against rotavirus gastroenteritis (RVGE).Methods4040 participants aged 6–12 weeks were enrolled and randomly assigned to either 3 oral doses of RV5 (n = 2020) or placebo (n = 2020), administered ∼4 weeks apart. The participants also received OPV and DTaP in a concomitant or staggered fashion. The primary objective was to evaluate vaccine efficacy (VE) against naturally-occurring RVGE at least 14 days following the third dose. Key secondary objectives included: VE against naturally-occurring severe RVGE and VE against severe and any-severity RVGE caused by rotavirus serotypes contained in the vaccine, occurring at least 14 days after the third dose. All adverse events (AEs) were collected for 30 days following each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. (ClinicalTrials.gov registry: NCT02062385).ResultsVE against RVGE of any-severity caused by any serotype was 69.3% (95% CI: 54.5, 79.7). The secondary efficacy analysis showed an efficacy of: 78.9% (95% CI: 59.1, 90.1) against severe RVGE caused by any serotype; 69.9% (95% CI: 55.2, 80.3) and 78.9% (95% CI: 59.1, 90.1) against any-severity and severe RVGE caused by serotypes contained in the vaccine, respectively. Within 30 days following any vaccination, 53.5% (1079/2015) and 53.3% (1077/2019) of participants reported at least one AE, and 5.8% (116/2015) and 5.7% (116/2019) reported SAEs in the vaccine and placebo groups, respectively. No SAEs were considered vaccine-related in recipients of RV5. Two intussusception cases were reported in recipients of RV5 who recovered after receiving treatment. Neither was considered vaccine-related.ConclusionsIn Chinese infants, RV5 was efficacious against any-severity and severe RVGE caused by any serotype and generally well-tolerated with respect to AEs.     

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.     

A short report on the highlights of world-wide development of RIX4414: a North American experience comparative evaluation of safety and immunogenicity of two dosages of an oral live attenuated human rotavirus vaccine (RIX4414) in infants in the United States and Canada

This randomized, double-blind trial conducted in the US and Canada was conducted to compare the safety and immunogenicity of two dosages of live attenuated oral monovalent G1 human rotavirus (HRV) vaccine administered orally at a 2-month interval concomitantly with routine childhood vaccines to healthy infants 5-15 weeks of age. No SAEs considered related to vaccine were reported. The incidence of solicited symptoms was similar among treatment groups during the 15-day post-vaccination surveillance periods. No significant difference in vaccine take after 2 doses (88.0% in high dose group and 81.5% in low dose group) was seen between vaccine groups. Two doses of either dosage level of HRV vaccine administered concurrently with routine childhood vaccines to healthy infants were well tolerated and elicited excellent vaccine takes.     

Immunodeficiency-associated vaccine-derived poliovirus type 3 in infant, South Africa, 2011

Patients with primary immunodeficiency are prone to persistently excrete Sabin-like virus after administration of live-attenuated oral polio vaccine and have an increased risk for vaccine-derived paralytic polio. We report a case of type 3 immunodeficiency-associated vaccine-derived poliovirus in a child in South Africa who was born with X-linked immunodeficiency syndrome.     

Evaluation of cost-effectiveness of live oral pentavalent reassortant rotavirus vaccine introduction in Ghana

Background

Globally, rotavirus gastroenteritis is the most common identifiable cause of severe diarrhea in children under 5. Recently introduced rotavirus vaccines from Merck &; Co. and GlaxoSmithKline have the potential to save hundreds of thousands of lives. Efficacy results in Ghana suggest Merck &; Co.’s live oral pentavalent rotavirus vaccine (RotaTeq^®) prevents 65.0% of severe gastroenteritis due to rotavirus infection in children under 5. The announcement by Merck and GSK to make their rotavirus vaccines available for developing nations at reduced prices provides Ghana with the opportunity to introduce rotavirus vaccines into the national immunization program after investigation of the medical, economic and political implications.

Methods

We estimated the average costs of treating children with diarrhea in the Ashanti region of Ghana as inpatients and outpatients. Using these results, data from rotavirus surveillance studies, and recent rotavirus vaccine efficacy evaluation, we estimated the cost-effectiveness of introducing RotaTeq in Ghana.

Results

Based on our prospective calculations, we estimated an average inpatient and outpatient costs of $233.97 and $17.09, respectively, for treating childhood diarrhea. Using the 2003 birth cohort, RotaTeq introduction could save 1554 lives and avert 93,109 disability-adjusted life-years (DALYs) annually. At a market price of $5 per dose, introducing RotaTeq would have a base-case cost of $62.26 per DALY averted, at a market price of $3.50 per dose, a base-case cost of $39.59 per DALY averted and at market cost of $1 per dose, a base-case cost of $1.81 per DALY averted. All three values are below the 2009 Ghana per capita GDP. Thus, RotaTeq introduction into Ghana will be very cost-effective. Sensitivity analyses suggest these results are robust.

Conclusions

RotaTeq vaccination for children under five in Ghana would be a highly cost-effective public health intervention. Ghanaian health officials should seek GAVI funding and evaluate how to maximize RotaTeq access.     

Uptake of oral rotavirus vaccine and timeliness of routine immunization in Brazil's National Immunization Program

Introduction

In March, 2006, oral rotavirus vaccine was added to Brazil's infant immunization schedule with recommended upper age limits for initiating (by age 14 weeks) and completing (by age 24 weeks) the two-dose series to minimize age-specific risk of intussusception following rotavirus vaccination. Several years after introduction, estimated coverage with rotavirus vaccine (83%) was lower compared to coverage for other recommended childhood immunizations (≥94%).

Methods

We analyzed data from Brazil's national immunization program on uptake of oral rotavirus vaccine by geographic region and compared administrative coverage estimates for first and second doses of oral rotavirus vaccine (Rota1 and Rota2) with first and second doses of diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine (DTP-Hib1 and DTP-Hib2). For 27 Brazilian cities, we compared differences between estimated rotavirus and DTP-Hib coverage in 2010 with delayed receipt of DTP-Hib vaccine among a cohort of children surveyed before rotavirus introduction.

Results

In 2010, infant vaccination coverage was 99.0% for DTP-Hib1 versus 95.2% for Rota1 (3.8% difference), and 98.4% for DTP-Hib2 versus 83.0% for Rota2 (15.4% difference), with substantial regional variation. Differences between DTP-Hib and rotavirus vaccination coverage in Brazilian cities correlated with delay in DTP-Hib vaccination among children surveyed. Age restrictions for initiating and completing the rotavirus vaccination series likely contributed to lower coverage with rotavirus vaccine in Brazil.

Conclusion

To maximize benefits of rotavirus vaccination, strategies are needed to improve timeliness of routine immunizations; monitoring rotavirus vaccine uptake and intussusception risk is needed to guide further recommendations for rotavirus vaccination.