Estimating the economic impact of pneumococcal conjugate,Haemophilus influenzae type b and rotavirus vaccines in India: National and state-level analyses

Background: To support vaccine decision-making we estimated from the societal perspective the potential health impact and costs averted through immunization with three vaccines – Haemophilus influenzae type b (Hib), pneumococcal conjugate vaccine (PCV) and rotavirus vaccine (RVV). Methods: Based on variability in disease burden, strength of health system and economic status, we selected four states in India: Bihar, New Delhi, Maharashtra and Tamil Nadu. We used secondary data sources to estimate the number of under-5 deaths averted from Hib, pneumococcus and rotavirus in each state and back-calculated the total cases averted. We synthesized available data to estimate the disease burden, treatment cost, caretaker productivity loss and vaccine coverage in each state. A Delphi Survey and roundtable among Indian experts was conducted to reach consensus on model inputs. Results: By scaling up coverage of Hib, PCV and RVV, India could save over US$1 billion (uncertainty range: US$0.9–US$2.4 billion) in economic benefits and avert more than 90,000 needless child deaths each year. An estimated US$1 billion (US$0.9–US$2 billion) or 88% of the total amount of cost savings would be attributable to lost productivity due to premature pneumococcal death. Another US$112.8 million (US$105–297 million), or 10% of the total cost would be accounted by costs related to loss of productivity due to disability as a result of these diseases. Treatment costs of Hib, pneumococcal disease and rotavirus gastroenteritis, would account for US$8.4 million (US$4–12 million) or <1% of the total costs of these diseases. Finally, caretaker productivity loss from seeking care would represent US$1.5 million (US$ 1–4.9 million). Cost savings varied by vaccine, coverage scenarios and states. Conclusions: Hib, PCV and RVV vaccine introduction in India can result in immediate benefits to the government and households in terms of savings.     

Response to conjugate pneumococcal and Haemophilus influenzae type b vaccines in asplenic patients

We determined the immunogenicity of conjugated Haemophilus influenzae type b and pneumococcal vaccines by quantitative analysis of the antibody response in asplenic patients. To that end, we vaccinated 92 patients with a conjugated Hib vaccine and 54 received two doses of conjugated pneumococcal vaccine (PCV7), followed at six months by a plain polysaccharide pneumococcal vaccine (PPV23). Antibody concentrations were measured before and three weeks after vaccination. After one dose of pneumococcal conjugate vaccine, 46% of the patients reached the antibody threshold of ≥1.0 μg/mL for all 7 tested vaccine serotypes. This percentage rose to 54% after the second dose of PCV7 and did not increase further after PPV23. Over 90% of patients had antibody concentrations ≥1.0 μg/mL for at least 5 out of the 7 conjugated pneumococcal serotypes after 2 doses of PCV7. For serotypes, included in the PPV23 vaccine only, 25% (PPS3)-100% (PPS19A) of the patients reached antibody concentrations ≥1.0 μg/mL after one dose of PPV23. For Hib, 97% of the patients reached the threshold concentration of ≥1.0 μg/mL after one dose of vaccine. It can be concluded that the majority of asplenic patients had a sufficient response to conjugated vaccines against Streptococcus pneumoniae and Hib, reflected by a ≥1.0 μg/mL antibody response. Inclusion of conjugated pneumococcal polysaccharide vaccines might be of additional value in the vaccination schedule for asplenic patients because of their high immunogenicity.     

Projected health benefits and costs of pneumococcal and rotavirus vaccination in Uganda

We determined impact and cost-effectiveness of pneumococcal and rotavirus vaccination programs among children < 5 years of age in Uganda from the public health system perspective. Disease-specific models compared the disease burden and cost with and without a vaccination program. If introduced, pneumococcal and rotavirus vaccine programs will save 10,796 and 5265 lives, respectively, prevent 94,071 Streptococcus pneumoniae and 94,729 rotavirus cases in children < 5 years, and save 3886 and 996 million Ugandan shillings ($2.3 and $0.6 million US dollars), respectively, in direct medical costs annually. At the GAVI price ($0.15/dose), pneumococcal vaccine will be cost-saving and rotavirus vaccine highly cost-effective.     

Attitudes and perceptions of private pediatricians regarding polio immunization in India

Background

India has faced considerable challenges in eradicating polio. Uttar Pradesh (UP) and Bihar are the two states in India where transmission of polio has never been interrupted. Private pediatricians are important stakeholders for vaccine delivery and maintaining public confidence in vaccines. The purpose of this study was to investigate the attitudes and perceptions of pediatricians in India regarding polio immunization and their opinions about various strategies regarding polio eradication in the country.

Methods

A random sample of 785 pediatricians belonging to the Indian Academy of Pediatrics (IAP) were selected for the survey with over sampling of members located in Bihar and UP. Potential participants were either contacted by phone or sent a self-administered anonymous questionnaire by mail. For this analysis both sets of responses were combined. Surveys were conducted from June 2009 to June 2010.

Results

A total of 398 surveys were completed (51%). Nearly all respondents indicated that polio eradication is still an important priority (99.7%). Ninety-six percent of pediatricians believed that strengthening routine immunization efforts remains the best way to eradicate polio in endemic areas. Other measures thought to be important in eradicating polio are mass campaigns with IPV (73%) and mass campaigns with bivalent OPV (59%). Pediatricians also identified several barriers to polio eradication which included parents’ lack of awareness of the importance of polio vaccination (88.8%), parents’ lack of confidence in polio vaccine (64.0%), religious beliefs (59.2%), fear of side effects (59.2%), lack of time or priority (56.6%), superstition (50.3%) and cultural beliefs (46.4%).

Conclusion

There is still strong support for polio eradication efforts among IAP members. Pediatricians in India strongly believe that improving the coverage of routine immunization remains the best way to eradicate polio. There is an urgent need to improve awareness, build confidence in the program, and remove barriers among parents.     

Pneumonia prevention: Cost-effectiveness analyses of two vaccines among refugee children aged under two years,Haemophilus influenzae type b-containing and pneumococcal conjugate vaccines,during a humanitarian emergency,Yida camp,South Sudan

By September 2013, war between Sudan and South Sudan resulted in >70,000 Sudanese refugees and high pneumonia incidence among the 20,000 refugees in Yida camp, South Sudan. Using Médecins Sans Frontières (MSF)-provided data and modifying our decision-tree models, we estimated if administering Haemophilus influenzae type b (Hib)-containing (pentavalent vaccine, also with diphtheria pertussis and tetanus [DPT] and hepatitis B) and pneumococcal conjugate (PCV) vaccines were cost-effective against hospitalized pneumonia. Among children <2 years old, compared with no vaccination, one- and two-doses of combined Hib-containing and PCV would avert an estimated 118 and 125 pneumonia cases, and 8.5 and 9.1 deaths, respectively. The cost per Disability-Adjusted-Life-Year averted for administering combined one- and two-doses was US$125 and US$209, respectively. MSF demonstrated that it was possible to administer these vaccines during an emergency and our analysis found it was highly cost-effective, even with just one-dose of either vaccine. Despite unknown etiology, there is strong field and now economic rationale for administering Hib and PCV during at least one humanitarian emergency.     

Antibodies against Haemophilus influenzae type b in The Gambia: Investigating the extent of protection across age groups

Following a landmark clinical trial, the vaccine against Haemophilus influenzae type b (Hib) was introduced in The Gambia in 1997. Whilst the immunogenicity of this vaccine is well established subsequent to the doses administered under the EPI schedule, little data exists assessing longevity of protection, using serology. Such data are needed however to predict the susceptibility to Hib at the population level.     

2008-2014年江苏省b型流感嗜血杆菌疫苗预防接种不良反应监测分析

摘要:目的　分析江苏省2008-2014年b型流感嗜血杆菌（Hib）疫苗预防接种不良反应的发生特征,评价Hib疫苗预防接种的安全性。方法　通过疑似预防接种异常反应信息管理系统和江苏省预防接种个案信息管理系统,收集江苏省2008-2014年报告的Hib疫苗不良反应个案数据和Hib疫苗接种数据,采用描述流行病学方法对相关指标进行分析。结果　2008-2014年江苏省共报告Hib疫苗不良反应5352例,平均报告发生率为77.98/10万剂,其中严重异常报告发生率为0.13/10万剂。所有不良反应中,一般反应4979例,占93.03%;异常反应373例,占6.97%。男、女性别比为1.51∶1,主要集中在≤1岁儿童和首剂接种后。一般反应的主要症状为发热、局部红肿和局部硬结,异常反应的诊断主要为过敏性皮疹。不良反应集中在接种后≤1d。结论　Hib疫苗不良反应以发热、红肿、硬结和过敏性皮疹为主,发生时间主要集中在接种后≤1 d。Hib疫苗具有较好的预防接种安全性,但仍需关注预防接种后急性过敏反应的发生信号。     

Comparison of serum bactericidal and antibody titers induced by two Haemophilus influenzae type b conjugate vaccines: A phase III randomized double-blind study

Haemophilus influenzae type b (Hib) conjugate vaccines have drastically reduced disease incidence worldwide. Protection against Hib infection has relied on the serum bactericidal activity (SBA) of antibodies to the Hib capsular polysaccharide (polyribosylribitol phosphate). However, licensure usually relies on measuring induction of antibodies to PRP as a surrogate for SBA. In a phase III clinical trial we compared a PRP-conjugate vaccine using the nontoxic diphtheria toxin mutant, CRM₁₉₇, as carrier protein with the licensed tetanus toxoid conjugate when administered subcutaneously as a three dose primary series in Japanese infants. As an addition to the phase III study, we have now evaluated SBA and show PRP-CRM₁₉₇ induces higher levels of SBA than PRP-T four weeks after the primary series, with a statistically significant correlation with anti-PRP titers. This data confirms the superior immunogenicity of PRP-CRM₁₉₇ compared with PRP-T assessed as SBA following a three-dose primary series by subcutaneous administration.Clinical trial registry: Registered on ClinicalTrials.gov (NCT01379846).     

Effect of HIV-exposure and timing of antiretroviral treatment initiation in children living with HIV on antibody persistence and memory responses to Haemophilus influenzae type b and pneumococcal polysaccharide-protein conjugate vaccines

BackgroundWe investigated the effect of in utero HIV-exposure, timing of antiretroviral treatment (ART) initiation, and ART interruption on memory responses and persistence of immunity induced by pneumococcal (PCV) and Haemophilus influenzae type b (HibCV) polysaccharide-protein conjugate vaccines.MethodsChildren were enrolled (6–12 weeks of age), and vaccinated with a three-dose primary series of 7-valent PCV (PCV7) and HibCV at 6, 10 and 14 weeks of age. Study groups included infants infected with HIV perinatally with CD4+ ≥ 25% initiating ART following immunological or clinical deterioration (ART-Def), or immediately upon enrolment followed by interruption at 40 (ART-Immed/40w) or 96 weeks (ART-Immed/96w); and HIV-uninfected infants with (HEU), and without HIV (HIV-unexpsoed) exposure in utero. Within each group, children were randomized to receive either a booster dose of PCV7 or HibCV at 15 months of age. PCV serotype-specific and polyribosyl ribitol phosphate (PRP) IgG were measured pre-boost, two-weeks post-boost and at two-years of age. Opsonophagocytic activity (OPA) to serotypes 9V, 19F and 23F was measured post-booster dose.ResultsPersistence of IgG to PCV vaccine–serotypes and anti-PRP was similar in all groups of children living with HIV (CLWH) compared to HIV-unexposed children. Anamnestic responses to PCV and HibCV were also similar in all three groups of CLWH compared to HIV-unexposed children. CLWH, however, tended to have lower functional antibody (OPA) titers than HIV-unexposed children after the PCV booster dose for some serotypes. Immunity to PCV and HibCV was similar between the ART-Immed/40w and ART-Immed-96w groups. There were no differences in IgG kinetics between HEU and HIV-unexposed children.ConclusionsA three dose primary series, with or without PCV or HibCV booster doses in CLWH initiated on ART during infancy, would likely be similarly effective in preventing invasive bacterial disease as in HIV-unexposed children.     

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.     

Randomised, controlled trial of concomitant pneumococcal and meningococcal conjugate vaccines

A randomised, open-label study compared the immunogenicity and safety of 7-valent pneumococcal conjugate vaccine (PCV7) and meningococcal C conjugate vaccine (MnCC vaccine) administered concomitantly and individually. Infants received PCV7 + MnCC vaccine (n = 265), PCV7 alone (n = 268) or MnCC vaccine alone (n = 178). PCV7 was administered at 2, 3½, 6 and 12 months, and MnCC vaccine at 2, 6 and 12 months. For the 7 pneumococcal serotypes tested (4, 6B, 9V, 14, 18C, 19F and 23F), proportions of subjects with pneumococcal serotype-specific immunoglobulin G (IgG) antibody concentrations ≥0.35 μg/mL post-infant series were non-inferior for the PCV7 + MnCC vaccine (91.5–99.6%) and PCV7 (89.0–99.6%) groups. Proportions of subjects achieving serogroup C meningococcal serum bactericidal assay titres ≥1:8 post-infant series were non-inferior for the PCV7 + MnCC vaccine (99.6%) and MnCC vaccine groups (98.8%). Pneumococcal IgG antibody levels were similar in the PCV7 + MnCC vaccine and PCV7 groups at each time point. Post-infant and post-toddler meningococcus C serum bactericidal assay titres and IgG levels were similar in the PCV7 + MnCC vaccine and MnCC groups, although pre-toddler, the levels were lower in the PCV7 + MnCC vaccine group than the MnCC vaccine group. Immune response rates to diphtheria antigen approached 100% for all vaccine groups. Local reactions were mostly similar among the treatment groups. The MnCC vaccine group had lower rates of some systemic events than the PCV7 + MnCC vaccine group. Immune responses to PCV7 + MnCC vaccine were non-inferior compared with those seen with each vaccine administered alone.     

Methods and challenges in measuring the impact of national pneumococcal and rotavirus vaccine introduction on morbidity and mortality in Malawi

BackgroundPneumonia and gastroenteritis are leading causes of vaccine-preventable childhood morbidity and mortality. Malawi introduced pneumococcal conjugate and rotavirus vaccines to the immunisation programme in 2011 and 2012, respectively. Evaluating their effectiveness is vital to ensure optimal implementation and justify sustained investment.Methods/DesignA national evaluation platform was established to determine vaccine effectiveness and impact in Malawi. Impact and effectiveness against vaccine-type invasive pneumococcal disease, radiological pneumonia and rotavirus gastroenteritis are investigated using before-after incidence comparisons and case-control designs, respectively. Mortality is assessed using a prospective population cohort. Cost-effectiveness evaluation is nested within the case-control studies. We describe platform characteristics including strengths and weaknesses for conducting vaccine evaluations.DiscussionIntegrating data from individual level and ecological methods across multiple sites provides comprehensive information for policymakers on programme impact and vaccine effectiveness including changes in serotype/genotype distribution over time. Challenges to robust vaccine evaluation in real-world conditions include: vaccination ascertainment; pre-existing rapid decline in mortality and pneumococcal disease in the context of non-vaccine interventions; and the maintenance of completeness and quality of reporting at scale and over time. In observational non-randomised designs ascertainment of vaccine status may be biased particularly in infants with fatal outcomes. In the context of multiple population level interventions targeting study endpoints attribution of reduced incidence to vaccine impact may be flawed. Providing evidence from several independent but complementary studies will provide the greatest confidence in assigning impact. Welcome declines in disease incidence and in child mortality make accrual of required sample sizes difficult, necessitating large studies to detect the relatively small but potentially significant contribution of vaccines to mortality prevention. Careful evaluation of vaccine effectiveness and impact in such settings is critical to sustaining support for vaccine programmes. Our evaluation platform covers a large population with a high prevalence of HIV and malnutrition and its findings will be relevant to other settings in sub-Saharan Africa.     

Bacterial meningitis and Haemophilus influenzae type b conjugate vaccine, Malawi

A retrospective database review showed that Haemophilus influenzae type b conjugate vaccine decreased the annual number of cases of H. influenzae type b meningitis in children in Blantyre, Malawi. Among young bacterial meningitis patients, HIV prevalence was high (36.7% during 1997-2009), and pneumococcus was the most common etiologic agent (57% in 2009).     

Longitudinal study on Streptococcus pneumoniae,Haemophilus influenzae and Staphylococcus aureus nasopharyngeal colonization in HIV-infected and -uninfected infants vaccinated with pneumococcal conjugate vaccine

BackgroundStreptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus are all potentially pathogenic, which frequently colonize the nasopharynx (NP) prior to causing disease.We studied bacterial NP-colonization in 321 HIV-infected and 243 HIV-uninfected children vaccinated with 7-valent pneumococcal conjugate vaccine (PCV7) at 6, 10 and 14 weeks of age.MethodsHIV-uninfected infants included those born to HIV-uninfected (HUU) and HIV-infected women (HEU); HIV-infected children with CD4+ lymphocyte ≥25% were randomized to initiate antiretroviral therapy immediately (ART-Immed) or when clinically indicated (ART-Def). Nasopharyngeal swabs for bacterial culture were taken prior to each PCV7 dose (Visits 1–3) and at 20, 39, 47 and 67 weeks of age (Visits 4–7). Swabs were cultured by standard methods and pneumococcal serotyping done by the Quellung method.ResultsColonization patterns for pneumococcus, H. influenzae and S. aureus did not differ between HUU and HEU children; and were also generally similar between ART-Def and ART-Immed children. Prevalence of PCV7-serotype colonization was similar between HIV-infected and HIV-uninfected children, however, overall pneumococcal and specifically non-vaccine serotype colonization tended to be lower in HIV-infected children. HIV-infected children also had a 44% lower prevalence of S. aureus colonization at Visit-1 (p = 0.010); and H. influenzae colonization was also lower among HIV-infected than HIV-uninfected children at Visit-2, Visit-3, Visit-6 and Visit-7.ConclusionVaccine-serotype colonization is similar in PCV-immunized HIV-infected and HIV-uninfected children. We, however, identified a lower prevalence of overall-pneumococcal and H. influenzae colonization in HIV-infected children post-PCV vaccination, the clinical-relevance of which warrants further study.     

Impact of Haemophilus influenzae type b conjugate vaccination on hospitalization for invasive disease in children fifteen years after its introduction in Italy

In Italy, Hib conjugate vaccine was introduced for infants in 1999 and included in the DTaP-HBV-IPV-Hib combination in 2001, with an uptake of 83.4% in 2002, >90% by 2005, and >95% by 2011. We estimated the impact of Hib vaccination on hospitalizations for H. influenzae invasive disease in children <5 years.Age-specific hospitalization rates and hospitalization risk ratios (HRRs) with 95%CI during 2001–2013 were calculated performing time-series analysis. The number of cases reported to the national surveillance of invasive bacterial diseases was compared to the number of hospitalizations between 2007–2013.Hospitalization rates declined from 2.3 in 2001 to 0.9 × 100,000 in 2002 (HRR = 0.4, 95%CI = 0.3–0.6, p < 0.05) among children 1–4 years and from 5.4 in 2001 to 2.4 × 100,000 in 2005 (HRR = 0.4, 95%CI = 0.2–0.9, p < 0.05) among infants.During 2007–2013: 401 cases were reported, 242 were typed, 12.4% were by serotype b; 861 hospital admissions were recorded. Applying the percentage of typed b strains retrieved from the surveillance to the number of hospitalizations for invasive H. influenzae disease, an estimated 107 episodes could be attributable to serotype b.These findings provided reassuring data on the impact of Hib vaccination on the burden of hospitalization for invasive disease in Italian children.     

Development and technology transfer of Haemophilus influenzae type b conjugate vaccines for developing countries

This paper describes the development of a Haemophilus influenzae type b (Hib) conjugate vaccine at the National Institute for Public Health and the Environment/Netherlands Vaccine Institute (RIVM/NVI, Bilthoven, The Netherlands), and the subsequent transfer of its production process to manufacturers in developing countries. In 1998, at the outset of the project, the majority of the world's children were not immunized against Hib because of the high price and limited supply of the conjugate vaccines, due partly to the fact that local manufacturers in developing countries did not master the Hib conjugate production technology. To address this problem, the RIVM/NVI has developed a robust Hib conjugate vaccine production process based on a proven model, and transferred this technology to several partners in India, Indonesia, Korea and China. As a result, emerging manufacturers in developing countries acquired modern technologies previously unavailable to them. This has in turn facilitated their approach to producing other conjugate vaccines. As an additional spin-off from the project, a World Health Organization (WHO) Hib quality control (QC) course was designed and conducted at the RIVM/NVI, resulting in an increased regulatory capacity for conjugate vaccines in developing countries at the National Regulatory Authority (NRA) level. For the local populations, this has translated into an increased and sustainable supply of affordable Hib conjugate-containing combination vaccines. During the course of this project, developing countries have demonstrated their ability to produce large quantities of high-quality modern vaccines after a successful transfer of the technology.     

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.     

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.