Search

Background: Histo-blood group antigen (HBGA) status may affect vaccine efficacy due to rotavirus strains binding to HBGAs in a P genotype-dependent manner. This study aimed to determine if HBGA status affected vaccine take of the G3P[6] neonatal vaccine RV3-BB., Methods: DNA was extracted from stool samples collected in a subset (n = 164) of the RV3-BB phase IIb trial in Indonesian infants. FUT2 and FUT3 genes were amplified and sequenced, with any single-nucleotide polymorphisms analyzed to infer Lewis and secretor status. Measures of positive cumulative vaccine take were defined as serum immune response (immunoglobulin A or serum-neutralizing antibody) and/or stool excretion of RV3-BB virus. Participants were stratified by HBGA status and measures of vaccine take., Results: In 147 of 164 participants, Lewis and secretor phenotype were determined. Positive vaccine take was recorded for 144 (97.9%) of 147 participants with the combined phenotype determined. Cumulative vaccine take was not significantly associated with secretor status (relative risk, 1.00 [95% CI, .94-1.06]; P = .97) or Lewis phenotype (relative risk, 1.03 [95% CI, .94-1.14]; P = .33), nor was a difference observed when analyzed by each component of vaccine take., Conclusions: The RV3-BB vaccine produced positive cumulative vaccine take, irrespective of HBGA status in Indonesian infants., Competing Interests: Potential conflicts of interest. Murdoch Children's Research Institute holds the license for the RV3-BB vaccine. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: 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., Methods: 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., Results: 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., Conclusion: 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)., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [J.F., R.M.S. and N.S.B. are employees of PT Bio Farma who provided funds to support this study and plan to manufacture RV3 rotavirus vaccine (Bio Farma). All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.]., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Rotavirus is a major cause of diarrhea in Indonesian children. However, rotavirus vaccines have not been introduced in the national immunization program of Indonesia. Understanding the genetic diversity and conserved antigenic regions of circulating strains are therefore essential to assess the potential efficacy of rotavirus vaccines. We collected fecal samples from hospitalized children less than 5 years of age with acute diarrhea. Rotavirus genotyping was performed by reverse transcriptase polymerase chain reaction, followed by sequencing of the VP4, VP7, and NSP4 genes of representative strains. Phylogenetic analysis was performed to investigate their relationship with globally circulating strains. Conservational analysis, immunoinformatics, and epitope mapping in comparison to vaccine strains were also performed. The sequence analyses showed that differences of multiple amino acid residues existed between the VP4, VP7, and NSP4 antigenic regions of the vaccine strains and the Indonesian isolates. However, many predicted conserved epitopes with higher antigenicity were observed in the vaccine and Indonesian strains, conferring the importance of these epitopes. The identified epitopes showed a higher potential of rotavirus vaccine to be employed in Indonesia. It could also be helpful to inform the design of a peptide vaccine based on the conserved regions and epitopes in the viral proteins., (© 2019 Wiley Periodicals, Inc.)

Rotaviruses and noroviruses are the most important viral causes of acute gastroenteritis in children. While previous studies of acute gastroenteritis in Indonesia mainly focused on rotavirus, here, we investigated the burden and epidemiology of norovirus and rotavirus disease. Children less than five years of age hospitalized with acute gastroenteritis were enrolled in this study from January to December 2015 at three participating hospitals. Rotavirus was detected by enzyme immunoassay (EIA), followed by genotyping by reverse transcription PCR (RT-PCR). Norovirus genogroups were determined by TaqMan-based quantitative RT-PCR. Among 406 enrolled children, 75 (18.47%), 223 (54.93%) and 29 (7.14%) cases were positive for norovirus, rotavirus and both viruses (mixed infections), respectively. Most cases clinically presented with fever, diarrhea, vomiting and some degree of dehydration. The majority (n = 69/75 [92%]) of the noroviruses identified belonged to genogroup II, and several genotypes were identified by sequencing a subset of samples. Among 35 samples tested for rotavirus genotype, the most prevalent genotype was G3P[8] (n = 30/35 [85.6%]). Our study suggests that the burden of norovirus diseases in Indonesian children should not be underestimated. It also shows the emergence of rotavirus genotype G3P[8] in Indonesia.

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: A strategy of administering a neonatal rotavirus vaccine at birth to target early prevention of rotavirus gastroenteritis may address some of the barriers to global implementation of a rotavirus vaccine., Methods: We conducted a randomized, double-blind, placebo-controlled trial in Indonesia to evaluate the efficacy of an oral human neonatal rotavirus vaccine (RV3-BB) in preventing rotavirus gastroenteritis. Healthy newborns received three doses of RV3-BB, administered according to a neonatal schedule (0 to 5 days, 8 weeks, and 14 weeks of age) or an infant schedule (8 weeks, 14 weeks, and 18 weeks of age), or placebo. The primary analysis was conducted in the per-protocol population, which included only participants who received all four doses of vaccine or placebo within the visit windows, with secondary analyses performed in the intention-to-treat population, which included all participants who underwent randomization., Results: Among the 1513 participants in the per-protocol population, severe rotavirus gastroenteritis occurred up to the age of 18 months in 5.6% of the participants in the placebo group (28 of 504 babies), in 1.4% in the neonatal-schedule vaccine group (7 of 498), and in 2.7% in the infant-schedule vaccine group (14 of 511). This resulted in a vaccine efficacy of 75% (95% confidence interval [CI], 44 to 91) in the neonatal-schedule group (P<0.001), 51% (95% CI, 7 to 76) in the infant-schedule group (P=0.03), and 63% (95% CI, 34 to 80) in the neonatal-schedule and infant-schedule groups combined (combined vaccine group) (P<0.001). Similar results were observed in the intention-to-treat analysis (1649 participants); the vaccine efficacy was 68% (95% CI, 35 to 86) in the neonatal-schedule group (P=0.001), 52% (95% CI, 11 to 76) in the infant-schedule group (P=0.02), and 60% (95% CI, 31 to 76) in the combined vaccine group (P<0.001). Vaccine response, as evidenced by serum immune response or shedding of RV3-BB in the stool, occurred in 78 of 83 participants (94%) in the neonatal-schedule group and in 83 of 84 participants (99%) in the infant-schedule group. The incidence of adverse events was similar across the groups. No episodes of intussusception occurred within the 21-day risk period after administration of any dose of vaccine or placebo, and one episode of intussusception occurred 114 days after the third dose of vaccine in the infant-schedule group., Conclusions: RV3-BB was efficacious in preventing severe rotavirus gastroenteritis when administered according to a neonatal or an infant schedule in Indonesia. (Funded by the Bill and Melinda Gates Foundation and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612001282875 .).

Background: Rotavirus has been identified as the most common pathogen associated with severe diarrhoea. Two effective vaccines against the pathogen have been licensed. However, many countries including Indonesia have yet to introduce the vaccine into their national immunisation programs. This study aimed to examine the attitudes of healthcare providers (HCPs) and other health stakeholders towards the pathogen and the vaccine., Methods: Semi-structured in-depth interviews were undertaken in two districts of Yogyakarta Province, Indonesia with nurses, midwives, primary care providers, pediatricians and other health stakeholders. Thematic analysis was undertaken., Results: Fourteen interviews were conducted between August and October 2013. We identified that while participants do not consider diarrhea to be an important problem in Indonesia, they do acknowledge that it can be serious if not properly treated. While the majority had some level of knowledge about rotavirus, not all participants knew that a vaccine was available. There were mixed feelings towards the need for the vaccine. Some felt that the vaccine is not ranked as a priority as it is not listed on the national program. However, others agreed there is a rationale for its use in Indonesia. The cost of the vaccine (when sold in the private sector) was perceived to be the primary barrier impacting on its use., Conclusions: The high cost and the low priority given to this vaccine by the public health authorities are the biggest obstacles impacting on the acceptance of this vaccine in Indonesia. HCPs need to be reminded of the burden of disease associated with rotavirus. In addition, reminding providers about the costs associated with treating severe cases versus the costs associated with prevention may assist with improving the acceptance of HCPs towards the vaccine. Promotion campaigns need to target the range of HCPs involved in the provision of care to infants and pregnant women.

Background: Diarrhea is a major public health concern throughout the world because the prevalence of morbidity of diarrhea has not changed significantly in the past decade. It remains the third leading cause of death among children less than 5 years of age. Recent surveillance studies have shown that rotavirus is a significant cause of pediatric hospitalization and death due to diarrhea. Indonesia has limited data on risk factors, disease burden, and deaths in children due to rotavirus diarrhea. The objective of this study was to examine the above mentioned factors related to rotavirus diarrhea in hospitalized children in Sanglah Hospital, Denpasar., Methods: A prospective cohort study was conducted at Sanglah Hospital Denpasar from April 2009 to December 2011. The present study was part of a nationwide study on Extension for Hospital-based Surveillance and Strain Characterization of Rotavirus Diarrhea Indonesia involving four hospitals throughout Indonesia as a part of the Asian Rotavirus Surveillance Network. We studied children aged <5 years who were hospitalized with acute diarrhea, and analyzed their stool samples using an immunoassay that detects the rotavirus antigen., Results: A total of 656 patients met the inclusion criteria for this study. Of 5805 patients under the age of 5 who were hospitalized between April 2009 and December 2011, the prevalence of diarrhea among hospitalized pediatric patients was 11.3% and the prevalence of rotavirus diarrhea was 49.8%. The male to female ratio of those affected by rotavirus was 1.6:1. The occurrence of vomiting was significantly higher in rotavirus diarrhea than in non-rotavirus diarrhea (RR, 1.4; 95% CI, 1.08 to 1.70; p = 0.004)., Conclusions: Diarrhea remains an important cause of hospitalization in children, and rotavirus was the most important etiology. We found that boys had a greatest risk of rotavirus infection than girls. Good nutritional status and breastfeeding provided the same protection against rotavirus and non-rotavirus diarrhea.

Introduction: Past experience with live oral vaccines including licensed rotavirus vaccines demonstrates a trend towards reduced vaccine efficacy in developing countries compared with developed countries. The reasons behind this disparity are not well understood. Transplacental transfer of maternal antibodies and breast milk ingestion may attenuate vaccine responses in infants in developing countries where rotavirus infections are endemic, and maternal antibody levels are high. We examined the prevalence and level of rotavirus antibody in maternal and cord serum, colostrum and breast milk in a developing country setting., Methods: 100 mother-infant pairs were prospectively recruited from December 2008 to February 2009 at Dr. Sardjito Hospital, Yogyakarta, Indonesia. Maternal and cord sera were collected during delivery. Colostrum and transitional breast milk were collected between day 0-3 and day 7-10 postpartum respectively. Rotavirus-specific IgA and IgG were estimated for all specimens and virus neutralization assays were conducted on a subset of milk specimens., Results: All maternal and cord serum samples were positive for rotavirus-specific IgG antibodies with a strong correlation between levels of rotavirus-specific IgG in mothers and levels transferred to infants in cord blood (r=0.86; p=0.001). 78% of colostrum and 67% of transitional breast milk specimens were positive for rotavirus-specific IgA. There was a median 4-fold decrease in rotavirus-specific IgA from colostrum to transitional breast milk. Neutralizing antibodies were present in 56% of colostrum specimens assayed (19/34) and in 41% of transitional milk specimens assayed (14/34)., Conclusions: Maternal serum and breast milk antibodies to rotavirus are highly prevalent in a developing country setting. Evaluation of the impact of maternal anti-rotavirus serum and breast milk antibody upon vaccine immunogenicity would help to inform rotavirus vaccination strategies, especially in developing settings., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

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.

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.

Globally, rotavirus is the leading cause of diarrhea-related hospitalizations and deaths among young children, but the burden of rotavirus disease in Indonesia is poorly documented. From January through December 2006, we conducted prospective surveillance (inpatient and outpatient) among children aged <5 years at 6 hospitals in 6 provinces of Indonesia, using standardized methodology. Of 2240 enrolled children hospitalized for diarrhea, 1345 (60%) were rotavirus positive. Of 176 children enrolled in outpatient clinics in 3 hospitals, 73 (41%) were rotavirus positive. Among children hospitalized for diarrhea, dehydration was more common among those who tested positive for rotavirus than among those who did not (91% vs 82%; P < .05), as was vomiting (86% vs 67%; P < .05). Children aged 6-23 months experienced 72% of all rotavirus episodes. Rotavirus prevalence increased slightly in the cool, dry season. The most commonly detected genotypes were G9 (30%) and P[6] (56%). G1P[6] and G9P[6] accounted for 34% and 21% of strains, respectively. A high proportion of genotype P[6] was detected, in combination with the common G types G1 and G9. Available rotavirus vaccines would likely be efficacious against the most common circulating strains, but continued monitoring of uncommon genotypes is needed.

Background: Globally, group A rotavirus causes significant morbidity and mortality among children. Limited data exist on the epidemiology of rotavirus disease among Indonesian children., Objectives: We describe the epidemiology of rotavirus-associated diarrhea among Indonesian children <6 years of age, including clinical symptoms and genotypes., Study Design: We conducted a hospital-based, case series study at four referral hospitals between February 2004 and February 2005 among children with diarrhea. Rotavirus positivity was defined by a positive result from either EIA or RT-PCR. A semi-nested RT-PCR was used to determine specific rotavirus genotypes., Results: 1660 stools were tested for pathogens. The overall rotavirus prevalence was 45.5%. Children with rotavirus-associated diarrhea were significantly younger (p<0.0001) and more likely to be hospitalized (81.3% versus 72.2%; p<0.0001). Symptoms associated with rotavirus included, vomiting, fever, nausea, fatigue and dehydration, while bloody stool was significantly less common with rotavirus-associated diarrhea., Conclusion: Rotavirus was an important contributor of morbidity to our study sample. Rotavirus genotyping demonstrated a temporal shift from G1-G4 to G9, but this was highly associated with the P[8] gene, suggesting that a multivalent rotavirus vaccine, incorporating G9 P[8] antigen, may reduce the burden of diarrheal illnesses among Indonesian children.

Rotavirus remains the most common cause of severe, dehydrating diarrhea among children worldwide. Several rotavirus vaccines are under development. Decisions about new vaccine introduction will require reliable data on disease impact. The Asian Rotavirus Surveillance Network, begun in 2000 to facilitate collection of these data, is a regional collaboration of 36 hospitals in nine countries or areas that conduct surveillance for rotavirus hospitalizations using a uniform World Health Organization protocol. We summarize the Network's organization and experience from August 2001 through July 2002. During this period, 45% of acute diarrheal hospitalizations among children 0-5 years were attributable to rotavirus, higher than previous estimates. Rotavirus was detected in all sites year-round. This network is a novel, regional approach to surveillance for vaccine-preventable diseases. Such a network should provide increased visibility and advocacy, enable more efficient data collection, facilitate training, and serve as the paradigm for rotavirus surveillance activities in other regions.

Nine different electropherotypes of rotaviruses occurred among 85 children with rotavirus diarrhea in Yogyakarta, Indonesia. Eighty percent of the electropherotypes had a "long" RNA pattern characteristic of human subgroup 2.