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Abstract: This study estimates rotavirus disease burden in children under age 3 years presenting with acute gastroenteritis to hospitals in Purworejo district and Yogyakarta city from August 2001 to April 2004. Among a total of 8929 hospitalized children, 1397 (16%) presented with acute gastroenteritis and of the 1321 stool samples tested, 705 (53%) were positive for rotavirus. Rotavirus infections were most common among children aged 7–23 months and rotavirus was more common during the dry season (June through August). Logistic regression analysis showed no differences in socioeconomic indicators between the rotavirus positive and negative admissions. Rotavirus vaccination may prevent a large proportion of all hospitalizations of young children under 3 years of age presenting with acute gastroenteritis. [Copyright &y& Elsevier]

Rotavirus (RV) remains the most common cause of morbidity and mortality due to acute gastroenteritis (AGE) in children under five. In Indonesia, RV is responsible for 60 % of severe AGE and 40 % of non-severe AGE in these children. This study assessed the cost-effectiveness of introduction of rotavirus vaccines (RVV) into the National Immunization Program in Indonesia. We conducted a cost-effectiveness analysis (CEA) of RVV introduction in Indonesia, assuming a three-dose vaccine schedule based on the planned introduction proposed by the Strategic Advisory Group of Experts on Immunization. The analysis involved an initial introduction of an imported RVV (Rotavac®, Bharat Biotech, India) followed by a staged implementation of the locally produced RVV (Bio Farma, Indonesia) from both health system and societal perspectives. The primary outcome measure was the incremental cost (2019 USD) per disability-adjusted life year (DALY) averted, compared to no vaccination. We took model inputs from an Indonesian cost-of-illness study, national information systems and scientific literature, covering disease incidence, hospitalization, mortality, healthcare costs, and vaccine related factors. Our analyses included univariate and probabilitistic sensitivity analyses to assess various parameters. The cost of a 10-year vaccination program is 82.6 million USD and can potentially prevent 7.3 million cases of rotavirus and 0.42 million DALYs. From a societal perspective, the incremental cost-effectiveness ratio (ICER) for the staged program is 464 USD per DALY averted (12 % of Indonesia's gross domestic product (GDP) per capita). From a healthcare sector perspective, ICER is similar at 479 USD (13 % GDP per capita). The introduction of RVV into the National Immunization Program is likely to be highly cost-effective in Indonesia. This work was supported by funding agreement with the Murdoch Children's Research Institute (MCRI), PATH, and the Indonesian Technical Advisory Group on Immunization (ITAGI). [ABSTRACT FROM AUTHOR]

Despite safe and effective WHO prequalified rotavirus vaccines, at least 84 million children remain unvaccinated. A birth dose schedule of the RV3-BB vaccine was reported to be highly efficacious against severe rotavirus disease in Indonesian infants and is under further development at PT Bio Farma, Indonesia. The aim is to develop a rotavirus vaccine starting from birth that could improve the implementation, safety, and effectiveness of vaccines. A multi-site phase I study of a human neonatal RV3 rotavirus vaccine (Bio Farma) in adults, children, neonates in Indonesia from April 2018 to March 2019. The adult and child cohorts were open-labeled single-dose, while the neonatal cohort was randomized, double-blind, and placebo-controlled three-doses at the age of 0–5 days, 8–10 weeks, and 12–14 weeks. The primary objective was to assess the safety of vaccines with the immunogenicity and vaccine virus fecal shedding as the secondary endpoints in neonates. Twenty-five adults, 25 children, and 50 neonates were recruited, and all but one in the neonatal cohort completed all study procedures. Three serious adverse events were reported (1 adult & 2 neonates), but none were assessed related to investigational product (IP). The neonatal vaccine group had a significantly higher positive immune response (cumulative seroconverted SNA and IgA) 28 days after three doses than those in the placebo group (72% vs. 16.7%, respectively). The GMT of serum IgA in the vaccine group was significantly higher at post IP dose 1 (p < 0.05) and post IP dose 3 (p < 0.001) compared to the placebo group. The trial results show that the RV3 rotavirus vaccine (Bio Farma) is well tolerated in all participant cohorts (adults, children, and neonates). Three doses of this vaccine administered in a neonatal schedule were immunogenic. These promising results support further clinical development of the RV3 rotavirus vaccine (Bio Farma). [ABSTRACT FROM AUTHOR]

• IgA in breast milk was not associated with reduced RV3-BB vaccine take in Indonesia. • IgG titre in cord blood was associated with lower vaccine immunogenicity after one, not three doses of vaccine. • RV3-BB vaccine appears to be able to be given with breast-feeding in high rotavirus disease burden settings. Placental or breast milk maternal antibodies can potentially reduce oral rotavirus vaccine efficacy in developing countries. We aimed to examine the relationship between the level of rotavirus specific immunoglobulin A (IgA) and neutralising antibodies (NA) in colostrum and breast milk and cord IgG, with cumulative vaccine take following one and three doses of oral RV3-BB rotavirus vaccine within a Phase IIb trial in Indonesia. 196 infants received three doses of RV3-BB in a randomized, double-blinded trial, using a neonatal schedule (first dose at 0–5 days of age, n = 61), an infant schedule (first dose at ~ 8 weeks of age, n = 67) or placebo (n = 68). Rotavirus specific IgA and NA in colostrum and breast milk, rotavirus specific cord IgG, Serum IgA and stool excretion were measured. There was little evidence of an association between IgA in colostrum or breast milk and cumulative vaccine take after three doses in the neonatal or infant groups. In the neonatal group, there was a negative association between IgG titre in cord blood and cumulative vaccine take (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.92–1.00; p = 0.03) and serum IgA response (OR 0.94; 95%CI 0.89–0.99; p = 0.02) after one dose of vaccine, which were not evident after three doses in the neonatal or infant groups. Amongst Indonesian infants we did not find an association between IgA in colostrum or breast milk and vaccine take after 3 doses of RV3-BB vaccine. Maternal rotavirus antibodies in breast milk appear to have minimal impact on RV3-BB vaccine take when administered with a short delay in breast-feeding in settings with a high rotavirus disease burden. [ABSTRACT FROM AUTHOR]

• Both OPV and rotavirus vaccines contain live, attenuated strains that replicate in the gut. • OPV and rotavirus vaccine co-administration has been associated with lower rotavirus immune responses. • RV3-BB is a novel human neonatal rotavirus vaccine that provides protection from rotavirus disease from birth. • OPV and RV3-BB co-administration did not reduce immunogenicity of either vaccine. • These findings support the use of RV3-BB where either OPV or IPV is used in the routine schedule. The 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. A 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. Sero-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). The 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. [ABSTRACT FROM AUTHOR]

Highlights • The annual prevalence of rotavirus remains high, nearly 50% of hospitalized children. • Rotavirus diarrhea occurred mostly in children under 2 years of age. • The most prevalent genotypes were G1P8 in 2010–2012 and G3P8 in 2013–2015. Abstract Context Rotavirus diarrhea is a common disease worldwide which mostly affects children under five years old. Rotavirus infection causes severe diarrhea and leads to substantial health care costs. In Indonesia the rotavirus vaccine has been available since 2011, however it has not been included into the National Immunization Program. This study aims to describe the proportion of rotavirus in children under 5 in Indonesia, the clinical characteristics of rotavirus infections, and the rotavirus strains circulating in the country during 2010–2015. Methods Children under five years of age with acute watery diarrhea were prospectively identified and enrolled through the active diarrhea surveillance system in 5 sites in four provinces in Indonesia during 2010–2015. The rotavirus specimens were tested using Enzyme Immunoassay. Bivariate logistic regression tests were performed to compare rotavirus positive and negative results with respect to the collected demographic and clinical variables. Results From January 2010 to December 2015, the average annual rotavirus prevalence among children hospitalized with acute watery diarrhea in four provinces in Indonesia was 47.5%. Rotavirus diarrhea occurred mostly in children under 2 years of age. Of all age groups, children aged 6–11 and 12–23 months had the highest prevalence of rotavirus diarrhea in all years (54.2% and 50.6%, respectively). This study found that the most prevalent of G and P genotypes were G1P8 in 2010 (63.2%), 2011 (64.1%) and 2012 (74.6%) and G3P8 in 2013 (49.7%), 2014 (82.5%) and 2015 (84.4%) Conclusions This study demonstrates that rotavirus is a major cause of diarrhea in hospitalized children in Indonesia. These findings highlight the need for inclusion of the rotavirus vaccine to the National Immunization Program in Indonesia. [ABSTRACT FROM AUTHOR]

Abstract: An economic evaluation was undertaken to assess the potential for introducing rotavirus vaccine into Indonesia''s National Immunization Program. For a projected birth cohort of 4.2 million children was followed until 5 years of age, a routine rotavirus vaccination programme could potentially avert 488,547 cases of diarrhoea treated in outpatient hospital facilities, 176,375 hospitalizations, and 8148 deaths. Assuming a cost of US$ 14 per vaccine course, the incremental cost-effectiveness ratio would equal US$ 120.46 per disability adjusted life years averted, making routine vaccination highly cost-effective given Indonesia''s Gross National Income per capita of US$ 1560. At a cost per vaccine course of US$ 3.79 (societal perspective) or US$ 2.70 (health-care system perspective), routine rotavirus vaccination could be potentially cost-saving in Indonesia. [Copyright &y& Elsevier]