Vaccine Take of RV3-BB Rotavirus Vaccine Observed in Indonesian Infants Regardless of HBGA Status.

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.

Intermittent screening and treatment for malaria complementary to routine immunisation in the first year of life in Papua, Indonesia: a cluster randomised superiority trial.

BACKGROUND: In Papua (Indonesia), infants with P. falciparum and/or P. vivax malaria are at risk of severe anaemia and death. We hypothesized that in an area of high malaria transmission, intermittent screening and treatment of infants with malaria (ISTi) will reduce morbidity compared to passive case detection (PCDi). METHODS: We conducted a cluster randomised, open label, superiority trial. A total of 21 clusters of village health posts (VHP) were randomised 1:1 to either IST for infants coinciding with 4 routine immunisation visits or PCDi. Healthy term infants born to consenting mothers enrolled into a maternal malaria cluster randomised trial were included in the study and followed for 12 months. Point of care malaria rapid diagnostic tests were used to detect peripheral parasitaemia at 2, 3, 4 and 9 months old in all infants in ISTi clusters and when symptomatic in PCDi clusters. Infants with detected peripheral parasitaemia were treated with dihydroartemisinin-piperaquine. The co-primary outcomes were the incidence rate of clinical malaria in the first year of life and the prevalence of parasitaemia at age 12 months. The incidence rate ratio and prevalence ratio between ISTi and PCDi were estimated using mixed-effects Poisson and log-binomial regression modelling (accounting for clustering at VHP level). RESULTS: Between May 2014 and February 2017, 757 infants were enrolled into the study, 313 into 10 ISTi clusters, and 444 into 11 PCDi clusters. Overall, 132 episodes of parasitaemia were detected, of whom 17 (12.9%) were in symptomatic infants. Over 12 months, the incidence rate (IR) of clinical malaria was 24 [95% CI, 10-50] per 1000 children-years at risk in the ISTi arm and 19 [95% CI, 8,38] per 1000 children-years in the PCDi arm (adjusted incidence rate ratio [aIRR] 1.77 [95% CI, 0.62-5.01]; p = 0.280). The prevalence of parasitaemia at 12 months was 13% (33/254) in the IST clusters and 15% (57/379) in the PCD clusters (adjusted prevalence ratio (aPR) = 0.92 (95% CI, 0.70-1.21), p = 0.55). There was no difference in the risk of anaemia between treatment arms. CONCLUSIONS: In high malaria transmission area outside of Africa, our study suggests that compared to PCDi, ISTi offers no significant benefit in reducing the risk of clinical malaria in infants born to women receiving effective protection from malaria during pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov NCT02001428 , registered on 20 Nov 2013.

Risk factors for healthcare-associated infection among children in a low-and middle-income country.

BACKGROUND: Healthcare-associated infections (HAI) are one of significant causes of morbidity and mortality. Evaluating risk factors associated with HAI are important to improve clinical outcomes. We aimed to evaluate the risk factors of HAI in children in a low-to middle-income country. METHODS: A prospective cohort study was conducted during 43 months at a teaching hospital in Yogyakarta, Indonesia. All consecutive patients admitted to pediatric ICU and pediatric wards > 48 h were eligible. Those eligible patients were observed daily to identify the presence of HAI based on CDC criteria. The risk factors of HAI were identified. Multivariable logistic regression was used to identify independent risk factors. RESULTS: Total of 2612 patients were recruited. Of 467 were diagnosed as HAI. The cumulative incidence of HAI was 17.9%. In the multivariable analysis; length of stay > 7 days, severe sepsis, use of urine catheter, central venous catheter (CVC), non-standardized antibiotics, and aged < 1 year were independently associated with increased risk of HAI with adjusted OR (95%CI): 5.6 (4.3-7.3), 1.9 (1.3-2.9), 1.9 (1.3-2.6), 1.8 (1.1-2.9), 1.6 (1.2-2.0), and 1.4 (1.1-1.8), respectively. CONCLUSIONS: This study found that length of stay > 7 days, use of urine catheter and CVC, non-standardized antibiotic use, aged < 1 year, and had a diagnosis of severe sepsis increased risk of HAI.

Human Neonatal Rotavirus Vaccine (RV3-BB) to Target Rotavirus from Birth.

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 .).

Predictive Factors for Cardiopulmonary Resuscitation Failure.

OBJECTIVES: Patients with chronic diseases are often admitted to the hospital through the emergency room of the hospital because of complaints of dyspnoea, urinary retention, decreased consciousness and cardiac arrest requiring resuscitation. The purpose of this study is to find predictive factors for failure of cardiopulmonary resuscitation (CPR) in patients of chronic diseases. MATERIALS AND METHODS: This cross-sectional study took medical records of patients who were carried out from primary healthcare center in Yogyakarta from 2017 to 2019. Bivariate statistical analysis used Fisher's exact test to determine the relative risk; if P < 0.25, then multivariate analysis with logistic regression continued with the backward method to obtain the odds ratio (OR). RESULTS: The results indicate that cardiac arrest patients with sepsis are most likely to fail at CPR, whereas male patients are 9.1 times (OR 9.1); patients with acidosis, 8.1 times (OR 8.1); and patients with asystole heart rhythm, 7.8 times (OR 7.8, P < 0.05). We can conclude that male patients with sepsis, acidosis or asystole heart rhythm will almost certainly fail to receive resuscitation. CONCLUSION: Sepsis or septic shock, the male gender, acidosis, and asystole rhythm can be determinants of mortality in patients with chronic diseases who undergo CPR. It is necessary for one to test the application of the checklist or data from other hospitals and score the predictive factors to make the determination of the success of CPR easier.

Malaria morbidity and mortality following introduction of a universal policy of artemisinin-based treatment for malaria in Papua, Indonesia: A longitudinal surveillance study.

BACKGROUND: Malaria control activities can have a disproportionately greater impact on Plasmodium falciparum than on P. vivax in areas where both species are coendemic. We investigated temporal trends in malaria-related morbidity and mortality in Papua, Indonesia, before and after introduction of a universal, artemisinin-based antimalarial treatment strategy for all Plasmodium species. METHODS AND FINDINGS: A prospective, district-wide malariometric surveillance system was established in April 2004 to record all cases of malaria at community clinics and the regional hospital and maintained until December 2013. In March 2006, antimalarial treatment policy was changed to artemisinin combination therapy for uncomplicated malaria and intravenous artesunate for severe malaria due to any Plasmodium species. Over the study period, a total of 418,238 patients presented to the surveillance facilities with malaria. The proportion of patients with malaria requiring admission to hospital fell from 26.9% (7,745/28,789) in the pre-policy change period (April 2004 to March 2006) to 14.0% (4,786/34,117) in the late transition period (April 2008 to December 2009), a difference of -12.9% (95% confidence interval [CI] -13.5% to -12.2%). There was a significant fall in the mortality of patients presenting to the hospital with P. falciparum malaria (0.53% [100/18,965] versus 0.32% [57/17,691]; difference = -0.21% [95% CI -0.34 to -0.07]) but not in patients with P. vivax malaria (0.28% [21/7,545] versus 0.23% [28/12,397]; difference = -0.05% [95% CI -0.20 to 0.09]). Between the same periods, the overall proportion of malaria due to P. vivax rose from 44.1% (30,444/69,098) to 53.3% (29,934/56,125) in the community clinics and from 32.4% (9,325/28,789) to 44.1% (15,035/34,117) at the hospital. After controlling for population growth and changes in treatment-seeking behaviour, the incidence of P. falciparum malaria fell from 511 to 249 per 1,000 person-years (py) (incidence rate ratio [IRR] = 0.49 [95% CI 0.48-0.49]), whereas the incidence of P. vivax malaria fell from 331 to 239 per 1,000 py (IRR = 0.72 [95% CI 0.71-0.73]). The main limitations of our study were possible confounding from changes in healthcare provision, a growing population, and significant shifts in treatment-seeking behaviour following implementation of a new antimalarial policy. CONCLUSIONS: In this area with high levels of antimalarial drug resistance, adoption of a universal policy of efficacious artemisinin-based therapy for malaria infections due to any Plasmodium species was associated with a significant reduction in total malaria-attributable morbidity and mortality. The burden of P. falciparum malaria was reduced to a greater extent than that of P. vivax malaria. In coendemic regions, the timely elimination of malaria will require that safe and effective radical cure of both the blood and liver stages of the parasite is widely available for all patients at risk of malaria.

Phylogenetic and immunoinformatic analysis of VP4, VP7, and NSP4 genes of rotavirus strains circulating in children with acute gastroenteritis in Indonesia.

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.

Norovirus and rotavirus infections in children less than five years of age hospitalized with acute gastroenteritis in Indonesia.

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.

Religious and community leaders' acceptance of rotavirus vaccine introduction in Yogyakarta, Indonesia: a qualitative study.

BACKGROUND: In Indonesia, oral rotavirus vaccines are available but not funded on the National Immunization Program (NIP). New immunization program introduction requires an assessment of community acceptance. For religiously observant Muslims in Indonesia, vaccine acceptance is further complicated by the use of porcine trypsin during manufacturing and the absence of halal labeling. In Indonesia, religious and community leaders and the Majelis Ulama Indonesia (MUI) are important resources for many religiously observant Muslims in decisions regarding the use of medicines, including vaccines. This study aimed to explore the views of religious and community leaders regarding the rotavirus vaccine to inform future communication strategies. METHODS: Twenty semi-structured in-depth interviews were undertaken with religious leaders and community representatives from two districts of Yogyakarta Province, Indonesia. Thematic analysis was undertaken. RESULTS: Although there was recognition childhood diarrhoea can be severe and a vaccine was needed, few were aware of the vaccine. Participants believed a halal label was required for community acceptance, and maintenance of trust in their government and leaders. Participants considered themselves to be key players in promoting the vaccine to the community post-labeling. CONCLUSIONS: This study highlights the need for better stakeholder engagement prior to vaccine availability and the potentially important role of religious and community leaders in rotavirus vaccine acceptability in the majority Muslim community of Yogyakarta, Indonesia. These findings will assist with the development of strategies for new vaccine introduction in Indonesia.

Clinical profile of congenital rubella syndrome in Yogyakarta, Indonesia.

BACKGROUND: Congenital rubella syndrome (CRS) has many severe neurological manifestations and other systemic consequences. Although various studies have been done in Indonesia, there are no conclusive results on CRS incidence. The aim of this study was therefore to investigate the incidence, clinical manifestations and outcomes of CRS in Yogyakarta, Indonesia. METHODS: A descriptive study involving a review of congenital anomalies associated with CRS was carried out at Dr Sardjito Hospital, Yogyakarta, Indonesia, from July 2008 to June 2013. CRS was categorized according to the World Health Organization (WHO) classification. This study involved children aged <1 year old, and was conducted at the outpatient clinic, pediatric and neonatology wards. RESULTS: A total of 201 children met the criteria for suspected CRS during the 5 year study. Of those patients, 6% were classified as having laboratory-confirmed CRS, 21.4% as having clinically compatible CRS, and 72.6% as having discarded CRS (i.e. a suspected case that does not meet the criteria for CRS). The estimated incidence of laboratory-confirmed CRS and laboratory-confirmed and clinically compatible CRS in Yogyakarta, Indonesia during the study period was 0.05:1,000 and 0.25:1,000 live births, respectively. Of the laboratory-confirmed CRS patients, 83.3% of children had congenital heart disease (CHD), 75% had hearing impairment, 66.7% had congenital cataract and 50% had microcephaly. Furthermore, none of the mothers was vaccinated against rubella. CONCLUSIONS: The incidence of CRS in infants in Yogyakarta Indonesia is considered high, with most clinical manifestations being CHD, hearing impairment and congenital cataract. This emphasizes the necessity for epidemiological study of CRS in other hospitals and the importance of establishing a national rubella vaccination program in Indonesia.

True Pathogen or Contamination: Validation of Blood Cultures for the Diagnosis of Nosocomial Infections in a Developing Country.

Background: Blood culture results are frequently used to guide antibiotic decision-making, but culture contaminants need to be distinguished from true pathogens. Aims: To assess the contamination rate of blood cultures and validate a method to distinguish between true bacteraemia and contamination. Methods: We analysed blood culture results from children who were admitted to the paediatric ICU and paediatric wards at the Sardjito Hospital, Yogyakarta, Indonesia between December 2010 and February 2013. For each positive culture result, the type of isolated organism, time to positivity, and the number of positive culture sites were considered to classify the isolate as representing a true bacteraemia or contaminant. Results: There were 1293 cultures obtained from blood and 308 (23.8%) were positive for bacterial growth. Fifty-three (4.1%) of the total cultures drawn fulfilled criteria for contaminants. The most common blood culture contaminants were coagulase-negative staphylococci. Conclusion: Using standardized criteria, it is possible to implement a working method to identify true nosocomial infection from blood culture contaminant, and thus limit the effect of contaminated blood culture on irrational antibiotic use.

Unsupervised primaquine for the treatment of Plasmodium vivax malaria relapses in southern Papua: A hospital-based cohort study.

BACKGROUND: Primaquine is the only licensed drug for eradicating Plasmodium vivax hypnozoites and, therefore, preventing relapses of vivax malaria. It is a vital component of global malaria elimination efforts. Primaquine is efficacious when supervised in clinical trials, but its effectiveness in real-world settings is unknown. We aimed to determine whether unsupervised primaquine was effective for preventing re-presentation to hospital with vivax malaria in southern Papua, Indonesia. METHODS AND FINDINGS: Routinely-collected hospital surveillance data were used to undertake a pragmatic comparison of the risk of re-presentation to hospital with vivax malaria in patients prescribed dihydroartemisinin-piperaquine (DHP) combined with primaquine versus those patients prescribed DHP alone. The omission of primaquine was predominantly due to 3 stock outages. Individual clinical, pharmacy, and laboratory data were merged using individual hospital identification numbers and the date of presentation to hospital. Between April 2004 and December 2013, there were 86,797 documented episodes of vivax malaria, of which 62,492 (72.0%) were included in the analysis. The risk of re-presentation with vivax malaria within 1 year was 33.8% (95% confidence Interval [CI] 33.1%-34.5%) after initial monoinfection with P. vivax and 29.2% (95% CI 28.1%-30.4%) after mixed-species infection. The risk of re-presentation with P. vivax malaria was higher in children 1 to <5 years of age (49.6% [95% CI 48.4%-50.9%]) compared to patients 15 years of age or older (24.2% [95% CI 23.4-24.9%]); Adjusted Hazard Ratio (AHR) = 2.23 (95% CI 2.15-2.31), p < 0.001. Overall, the risk of re-presentation was 37.2% (95% CI 35.6%-38.8%) in patients who were prescribed no primaquine compared to 31.6% (95% CI 30.9%-32.3%) in those prescribed either a low (≥1.5 mg/kg and <5 mg/kg) or high (≥5 mg/kg) dose of primaquine (AHR = 0.90 [95% CI 0.86-0.95, p < 0.001]). Limiting the comparison to high dose versus no primaquine in the period during and 12 months before and after a large stock outage resulted in minimal change in the estimated clinical effectiveness of primaquine (AHR 0.91, 95% CI 0.85-0.97, p = 0.003). Our pragmatic study avoided the clinical influences associated with prospective study involvement but was subject to attrition bias caused by passive follow-up. CONCLUSIONS: Unsupervised primaquine for vivax malaria, prescribed according to the current World Health Organization guidelines, was associated with a minimal reduction in the risk of clinical recurrence within 1 year in Papua, Indonesia. New strategies for the effective radical cure of vivax malaria are needed in resource-poor settings.

Hospital-based surveillance of congenital rubella syndrome in Indonesia.

Congenital rubella syndrome (CRS) has serious consequences, such as miscarriage, stillbirth, and severe birth defects in infants, resulting from rubella virus infection during pregnancy. However, rubella vaccine has not yet been implemented in Indonesia. This study aimed (1) to estimate the incidence of CRS in Indonesia, (2) describe the clinical features of CRS at our referral hospital, and (3) pilot a CRS surveillance system to be extended to other hospitals. We conducted a 4-month prospective surveillance study of infants aged <1 year with suspected CRS in 2013 at an Indonesian hospital. Infants with suspected CRS were examined for rubella-specific IgM antibody or rubella IgG antibody levels. Of 47 suspected cases of CRS, 11/47 (23.4%), 9/47 (19.1%), and 27/47 (57.5%) were diagnosed as laboratory-confirmed, clinically compatible, and discarded CRS, respectively. The most common defects among laboratory-confirmed CRS cases were hearing impairment (100%), congenital cataracts (72.7%), microcephaly (72.7%), and congenital heart defects (45.5%). CONCLUSION: The number of laboratory-confirmed CRS cases among Indonesian infants is high. Furthermore, hearing impairment is the most common clinical feature of CRS in infants. Our findings indicate the importance of implementation of rubella vaccine in Indonesia. Conducting hospital-based surveillance of CRS in other hospitals in Indonesia may be appropriate. What is Known: •Congenital rubella syndrome (CRS) has serious consequences in infants resulting from rubella virus infection during pregnancy. •The incidence of CRS in most developed countries has greatly decreased since implementation of rubella vaccination. •Rubella vaccine has not yet been implemented in many developing countries. What is New: •The number of laboratory-confirmed CRS cases among Indonesian infants was high. •Implementation of rubella vaccine into immunization programs in Indonesia is important because of the high number of CRS cases. •Our study highlights the need for ongoing prospective surveillance of CRS in Indonesia.

ANTIBIOTIC RESISTANCE AND MORTALITY IN CHILDREN WITH NOSOCOMIAL BLOODSTREAM INFECTION IN A TEACHING HOSPITAL IN INDONESIA.

Nosocomial infection is a major problem in hospitals worldwide. Understanding patterns of bacterial etiology and antibiotic susceptibility are important factors to combating nosocomial infection. Among children with nosocomial bloodstream infection (BSI), we identified pathogens and determined antibiotics resistance patterns and mortality rates for antibiotic-susceptible and multidrugresistant (MDR) infection in patients with nosocomial BSI in pediatric wards and PICU at Dr Sardjito Hospital, Indonesia during December 2010 to February 2013. Of 174 isolates from 170 patients, 168 pathogens were bacteria, of which 148 were gram-negative. Pseudomonas aeruginosa, Klebsiella spp, Enterobacteriaceae, Acinetobacter baumanii, and Escherichia coli was found in 55%, 6%, 4%, 1%, and <1%, respectively of the isolates. Imipenem, amikacin, ciprofloxacin, and ceftazadime had the highest sensitivity to nosocomial pathogens at 86%, 84%, 84%, and 75%, respectively. Eleven patients had MDR-infections, 7 of whom died. Among 153 patients infected with bacteria resistant to <3 classes of antibiotics (non-MDR), mortality was 40%, and among 4 patients with fully drug-susceptible sepsis only one died. Thus, substantial mortality was observed in children with nosocomial-BSI, particularly with MDR pathogens. Given the further high risk of resistance with wider use of carbapenems, third generation cephalosporins and flouroquinolones, prevention should be given highest priority in combating hospital-acquired infection.

Knowledge and attitudes towards rotavirus diarrhea and the vaccine amongst healthcare providers in Yogyakarta Indonesia.

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.

What works to improve duration of exclusive breastfeeding: lessons from the exclusive breastfeeding promotion program in rural Indonesia.

The aim of the study was to identify determinants of exclusive breastfeeding (EBF) at the individual, family, community, and organizational level. This study was a secondary analysis of data from a multilevel promotion of EBF program in two rural public health centers (PHCs) in the Demak district, Central Java, Indonesia. The program was a quasi-experimental study with a pretest-posttest control group. A total of 599 participants were enrolled, consisting of 163 mother infant pairs, 163 fathers, 163 grandmothers, 82 community leaders, and 28 midwives. EBF duration and its determinants were measured and analyzed using Cox proportional-hazard model. Mothers with a high level of breastfeeding knowledge had the greatest EBF duration. Mothers who had a knowledge score >80 had a 73 % (HR 0.27, 95 % CI 0.15, 0.48) greater chance of EBF compared to mothers who had a knowledge score of <60. Factors which shortened EBF duration were grandmother's lack of support for EBF (HR 2.04, 95 % CI 1.33, 3.14), received formula samples at discharge (HR 1.99, 95 % CI 1.25, 3.16), and maternal experience of breast engorgement (HR 1.97, 95 % CI 1.32, 2.94). High maternal breastfeeding knowledge was the only factor associated with longer duration of EBF. Barriers to EBF were breast engorgement, receiving formula samples at discharge, and a grandmother's lack of support for EBF.

Risk factors of rotavirus diarrhea in hospitalized children in Sanglah Hospital, Denpasar: a prospective cohort study.

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.

Direct and indirect costs of acute diarrhea in children under five years of age in Indonesia: Health facilities and community survey.

BACKGROUND: Diarrhea remains a major cause of child morbidity and mortality in low- and middle-income countries. Reliable data on the economic burden of diarrhea is required to support the selection of appropriate health intervention programs. This study aimed to estimate the costs of acute diarrhea in children under five years of age in Indonesia, a large middle-income country with a substantial diarrheal burden. METHODS: Direct medical cost data were extracted retrospectively for 1050 children under five years of age with acute diarrhea receiving inpatient care across 45 health facilities in seven Indonesian provinces during 2017-2020. Direct medical costs for children treated in outpatient settings were estimated by collecting unit costs associated with standard diarrhea case management in children. A structured interview of 240 caregivers of inpatients was also conducted retrospectively to estimate direct non-medical costs as well as indirect costs from caregiver income loss. RESULTS: The weighted average direct medical cost for treatment of acute diarrhea as an inpatient and outpatient across health facility types was US$99.8 (SD±$56.8)(35% room costs, 29% professional fees, 26% medication costs, 10% diagnostic costs) and US$7.6 (SD±$4.3) (34% diagnostic costs, 28% medication costs, 27% professional fees, 10% registration fees), respectively. The average direct non-medical household cost for an acute diarrheal admission was US$4.90 and the indirect cost was US$9.90. CONCLUSION: There is a significant economic burden associated with acute diarrhea in children in Indonesia. This study, based on a wide variety of health care settings and geographical regions, provides data to inform the economic evaluation of rotavirus vaccines and other diarrheal prevention programs. FUNDING: This work was supported by a research grant from the Murdoch Children's Research Institute (MCRI) and PATH; and the Indonesian Technical Advisory Group on Immunization (ITAGI).

Evaluation of stool microbiota signatures in two cohorts of Asian (Singapore and Indonesia) newborns at risk of atopy.

BACKGROUND: Studies have suggested that demographic and lifestyle factors could shape the composition of fecal microbiota in early life. This study evaluated infant stool microbiota signatures in two Asian populations, Singapore (n = 42) and Indonesia (n = 32) with contrasting socioeconomic development, and examined the putative influences of demographic factors on these human fecal associated bacterial signatures. RESULTS: Longitudinal analysis showed associations of geographical origin with Clostridium leptum, Atopobium and Bifidobacterium groups. Mode of delivery had the largest effect on stool microbiota signatures influencing the abundance of four bacterial groups. Significantly higher abundance of bacterial members belonging to the Bacteroides-Prevotella, Bifidobacterium and Atopobium groups, but lower abundance of Lactobacilli-Enterococci group members, were observed in vaginal delivered compared to caesarean delivered infants. Demographic factors influencing the structure of infants stool microbiota during the first year of life included breastfeeding, age of weaning, sibship size and exposure to antibiotics. CONCLUSIONS: Differences in stool microbiota signatures were observed in relation to various demographic factors. These features may confound studies relating to the association of the structure of fecal microbiota and the predisposition to human modern disease.

The incidence of acute respiratory infection in Indonesian infants and association with vitamin D deficiency.

BACKGROUND: Vitamin D deficiency has been associated with acute respiratory infection (ARI) in early life, but this has not been evaluated in Indonesia. We aimed to determine the incidence of ARI in Indonesian infants, and to evaluate the association with vitamin D deficiency. METHODS: From 23 December 2015 to 31 December 2017, we conducted a community-based prospective cohort study in Yogyakarta province. We enrolled 422 pregnant women and followed their infants from birth until 12 months of age for ARI episodes. Vitamin D status was measured at birth and at age six months. We performed Cox proportional hazard regression analysis to evaluate the association between vitamin D deficiency and pneumonia incidence. RESULTS: At study completion, 95% (400/422) of infants retained with a total of 412 child years of observation (CYO). The incidence of all ARI and of WHO-defined pneumonia was 3.89 (95% CI 3.70-4.08) and 0.25 (95% CI 0.21-0.30) episodes per CYO respectively. Vitamin D deficiency at birth was common (90%, 308/344) and associated with more frequent episodes of ARI non-pneumonia (adjusted odds ratio 4.48, 95% CI:1.04-19.34). Vitamin D status at birth or six months was not associated with subsequent pneumonia incidence, but greater maternal sun exposure during pregnancy was associated with a trend to less frequent ARI and pneumonia in infants. CONCLUSION: ARI, pneumonia, and vitamin D deficiency at birth were common in Indonesian infants. Minimising vitamin D deficiency at birth such as by supplementation of mothers or safe sun exposure during pregnancy has the potential to reduce ARI incidence in infants in this setting.