Differences in Micronutrient Intakes of Exclusive and Partially Breastfed Indonesian Infants from Resource-Poor Households are Not Accompanied by Differences in Micronutrient Status, Morbidity, or Growth.

BACKGROUND: When maternal micronutrient intakes and statuses are compromised, reductions in micronutrient concentrations in neonatal stores and human milk may result in suboptimal micronutrient intakes, statuses, and functional outcomes of breastfed infants during the critical first 6-month period. OBJECTIVES: We compared the adequacy of micronutrient intakes and statuses at 2 and/or 5 months and morbidity and growth faltering at 2, 5, and 12 months in a cohort of exclusively breastfed (EBF) and partially breastfed (PBF) infants from low-resource Indonesian households. METHODS: At 2 and 5 months, the breastfeeding status and human milk intake of 212 infants were determined using the deuterium oxide dose-to-mother technique, and intakes were calculated from milk micronutrient concentrations and 3-d weighed food intakes. At 5 months, five infant micronutrient biomarkers, hemoglobin, C-reactive protein, and α-1-acid-glycoprotein were measured. Infant morbidity, weight, and length were measured at 2, 5, and 12 months. Means, medians, or proportions were reported for each group and differences between groups were statistically determined. RESULTS: Median intakes of iron, thiamin, niacin, and vitamin B-12 were higher in PBF than EBF infants at 5 months (all P values < 0.05), but intakes in all infants were below adequate intakes. At 5 months, anemia was <20% in both groups, although fewer PBF versus EBF infants had vitamin B-12 deficiency (11.5% vs. 28.6%, respectively; P = 0.011). The mean ± SD length-for-age z-scores for EBF versus PBF infants at 2 months were 0.7 ± 0.9 versus -0.5 ± 1.1, respectively  (P = 0.158), declining to -1.4 ± 0.9 versus -1.1 ± 1.2, respectively, at 12 months (P = 0.059). Reported morbidity rates were generally low, with no evidence of a difference between infant groups (all P values > 0.126). CONCLUSIONS: Irrespective of exclusive or partial breastfeeding status, micronutrient intakes of infants were low, statuses were compromised, and growth faltering during the critical 6 months period of early infancy was present. The findings highlight the importance of improving maternal nutritional statuses and evaluating their impacts on infant outcomes.

Examination of Carbohydrate Products in Feces Reveals Potential Biomarkers Distinguishing Exclusive and Nonexclusive Breastfeeding Practices in Infants.

BACKGROUND: The stable isotope deuterium dose-to-mother (DTM) technique to estimate nonbreast milk water intake demonstrates that maternal self-report methods of infant feeding overestimate the true prevalence of exclusively breastfeeding practices. OBJECTIVE: We aimed to determine potential monosaccharide and oligosaccharide markers that distinguish between exclusively breastfed (EBF) versus nonexclusively breastfed (non-EBF) infants utilizing LC-MS-based methods. METHODS: Data for the analysis were collected as part of a larger, longitudinal study of 192 breastfed Indonesian infants aged 2 mo and followed up at 5 mo. Feces samples were collected from infants aged 2 mo (n = 188) and 5 mo (n = 184). EBF and non-EBF strata at each time point were determined via the DTM technique. Feces samples were analyzed to determine monosaccharide content using ultra-high-performance LC-triple quadrupole MS (UHPLC-QqQ MS). Relative abundances of fecal oligosaccharides were determined using nano-LC-Chip-quadrupole time-of-flight MS (nano-LC-Chip-Q-ToF MS). RESULTS: At age 2 mo, monosaccharide analysis showed the abundance of fructose and mannose were significantly higher (+377% and +388%, respectively) in non-EBF compared with EBF infants (P <0.0001). Fructose and mannose also showed good discrimination with areas under the curve (AUC) of 0.86 and 0.82, respectively. Oligosaccharide analysis showed that a 6-hexose (Hex6) isomer had good discrimination (AUC = 0.80) between EBF and non-EBF groups at 5 mo. CONCLUSION: Carbohydrate products, particularly fecal mono- and oligosaccharides, differed between EBF and non-EBF infants aged under 6 mo and can be used as potential biomarkers to distinguish EBF versus non-EBF feeding practices.

Impaired glucose tolerance among adolescents with low birth weight history: The Tanjungsari Cohort Study in Indonesia.

BACKGROUND AND OBJECTIVES: Diabetes prevalence has been increasing overtime in Indonesia along with its complications and morbidities. Diabetes prevention program is still a challenge. Previous study concluded poor intrauterine nutritional status, low birth weight (LBW), and nutrition status early in life were risk factors for impaired glucose tolerance (IGT) or type 2 diabetes mellitus in adulthood. This study aimed to evaluate the association between both LBW and intrauterine growth restriction (IUGR) with IGT in adolescents. METHODS AND STUDY DESIGN: Total of 536 subjects from Tanjungsari Cohort Study were included in this study. Subjects were in their early adolescence age (12-14 years). Anthropometric data were collected and IGT was determined by using 2- hour postprandial plasma glucose level, then it was assessed based on their birth weight and intrauterine nutritional status. RESULTS: Subjects with LBW history were shorter, had lower body weight and body mass index (p<0.05, respectively). The proportion of IGT is significantly higher among subject with LBW (RR 1.692 [1.079- 2.653]). There was no difference on proportion of IGT among subjects with IUGR compared with subjects who were not IUGR or born preterm (p=0.286). Multiple regression analysis showed the effect of LBW remain independent after adjusted with sex and socioeconomic variables (RR 1.650 [1.054-2.584]). CONCLUSIONS: Significant association was found between LBW and IGT in comparison to those who were born with normal birth weight. Hence, diabetes should be prevented as early as possible, even since in the pregnancy.

Fecal Microbiotas of Indonesian and New Zealand Children Differ in Complexity and Bifidobacterial Taxa during the First Year of Life.

The biological succession that occurs during the first year of life in the gut of infants in Western countries is broadly predictable in terms of the increasing complexity of the composition of microbiotas. Less information is available about microbiotas in Asian countries, where environmental, nutritional, and cultural influences may differentially affect the composition and development of the microbial community. We compared the fecal microbiotas of Indonesian (n = 204) and New Zealand (NZ) (n = 74) infants 6 to 7 months and 12 months of age. Comparisons were made by analysis of 16S rRNA gene sequences and derivation of community diversity metrics, relative abundances of bacterial families, enterotypes, and cooccurrence correlation networks. Abundances of Bifidobacterium longum subsp. infantis and B. longum subsp. longum were determined by quantitative PCR. All observations supported the view that the Indonesian and NZ infant microbiotas developed in complexity over time, but the changes were much greater for NZ infants. B. longum subsp. infantis dominated the microbiotas of Indonesian children, whereas B. longum subsp. longum was dominant in NZ children. Network analysis showed that the niche model (in which trophic adaptation results in preferential colonization) of the assemblage of microbiotas was supported in Indonesian infants, whereas the neutral (stochastic) model was supported by the development of the microbiotas of NZ infants. The results of the study show that the development of the fecal microbiota is not the same for infants in all countries, and they point to the necessity of obtaining a better understanding of the factors that control the colonization of the gut in early life.IMPORTANCE This study addresses the microbiology of a natural ecosystem (the infant bowel) for children in a rural setting in Indonesia and in an urban environment in New Zealand. Analysis of DNA sequences generated from the microbial community (microbiota) in the feces of the infants during the first year of life showed marked differences in the composition and complexity of the bacterial collections. The differences were most likely due to differences in the prevalence and duration of breastfeeding of infants in the two countries. These kinds of studies are essential for developing concepts of microbial ecology related to the influence of nutrition and environment on the development of the gut microbiota and for determining the long-term effects of microbiological events in early life on human health and well-being.

Development of a nutrient quality score for the complementary diets of Indonesian infants and relationships with linear growth and stunting: a longitudinal analysis.

Reducing multifactorial stunting is a priority for the 2025 WHO Global Nutrition Target. In the plant-based complementary diets of low-income countries, deficits in several growth-limiting micronutrients may contribute to stunting. Hence the intercorrelation between multiple micronutrients in terms of their intake and impact is important. Therefore, our aim was to develop a nutrient quality score using principal component analysis (PCA) in a sample of Indonesian infants at 6, 9 and 12 months of age and to evaluate the association of the scores with linear growth and stunting. At 6 months, 217 infants were recruited from Sumedang District, West Java, with 195 and 189 followed at 9 and 12 months of age, respectively. Complementary food intakes were assessed using 2-d weighed food records. Eight correlated nutrients (vitamin A, ascorbic acid, thiamine, riboflavin, niacin, Ca, Fe and Zn) were summarised using PCA into a single nutrient pattern that explained 56-65 % of the total variability. Nutrient quality scores were related to demographic, inflammation and complementary food indicator variables in hypothesised directions. While no significant relationships were apparent with linear growth, the odds of being stunted at ages 9 and 12 months was lower for infants with a higher nutrient quality score at 9 months (OR 0·75, 95 % CI 0·59, 0·95 and OR 0·69, 95 % CI 0·55, 0·88), respectively, for the fully adjusted models. A data-driven nutrient quality score is a valid tool to assess the influence of nutrient quality on stunting in at-risk infants.

Development of a nonlinear hierarchical model to describe the disposition of deuterium in mother-infant pairs to assess exclusive breastfeeding practice.

The World Health Organization recommends exclusive breastfeeding (EBF) for the first 6 months after birth. The deuterium oxide dose-to-the-mother (DTM) technique is used to distinguish EBF based on a cut-off (< 25 g/day) of water intake from sources other than breastmilk. This value is based on a theoretical threshold and has not been verified in field studies. The aim of this study was to estimate the water intake cut-off value that can be used to define EBF practice. One hundred and twenty-one healthy infants, aged 2.5-5.5 months who were deemed to be EBF were recruited. After administration of deuterium to the mothers, saliva was sampled from mother and infant pairs over a 14-day period. Validation of infant feeding practices was conducted via home observation over six non-consecutive days with caregiver recall. A fully Bayesian framework using a gradient-based Markov chain Monte Carlo approach implemented in Stan was used to estimate the cut-off of non-milk water intake of EBF infants. From the original data set, 113 infants were determined to be EBF and provided 1500 paired mother-infant observations. The deuterium saliva concentrations were best described by two linked 1-compartment models (mother and infant), with body weight as a covariate on the mother's volume of distribution and infant's body weight on infant's water clearance rate. The cut-off value was based on the 90th percentile of the posterior distribution of non-milk water intake and was 86.6 g/day. This cut-off value can be used in future field studies in other geographic regions to determine exclusivity of breast feeding practices in order to determine their potential public health needs.

Iron, zinc, vitamin A and selenium status in a cohort of Indonesian infants after adjusting for inflammation using several different approaches.

Inflammation confounds the interpretation of several micronutrient biomarkers resulting in estimates that may not reflect the true burden of deficiency. We aimed to assess and compare the micronutrient status of a cohort of Indonesian infants (n 230) at aged 6, 9 and 12 months by ignoring inflammation (unadjusted) and adjusting four micronutrient biomarkers for inflammation with C-reactive protein (CRP) and α-1-glycoprotein (AGP) using the following methods: (1) arithmetic correction factors with the use of a four-stage inflammation model; and (2) regression modelling. Prevalence of infants with any inflammation (CRP>5 mg/l and/or AGP>1 g/l) was about 25% at each age. Compared with unadjusted values, regression adjustment at 6, 9 and 12 months generated the lowest (P50 % across all ages. In conclusion, without inflammation adjustment, Fe deficiency was grossly under-estimated and vitamin A and Zn deficiency over-estimated, highlighting the importance of correcting for the influence of such, before implementing programmes to alleviate micronutrient malnutrition. However, further work is needed to validate the proposed approaches with a particular focus on assessing the influence of varying degrees of inflammation (i.e. recurrent acute infections and low-grade chronic inflammation) on each affected nutrient biomarker.

Effects of decentralisation and health system reform on health workforce and quality-of-care in Indonesia, 1993-2007.

The impact of decentralisation, socioeconomic changes and healthcare reforms in Indonesia on type and distribution of healthcare providers and quality-of-care has been unclear. We examined workforce trends for healthcare facilities from 1993 to 2007 using the Indonesian Family Life Surveys. Each included a sample of public and private healthcare facilities, used standardised interviews for numbers and composition of staffing, and quality-of-care vignettes. There was an increase in multiprovider facilities and shift in profile of solo providers-increasing proportions of midwives and drop in doctors in rural areas (including facilities with doctors) and nurses in urban areas. Quality-of-care scores were low, particularly for nurses as solo providers. Despite increased numbers of healthcare workers and growth of the private sector, outer Java-Bali and rural areas continued to be disadvantaged in workforce capacity and quality-of-care. The results have implications for accreditation and in-service training requirements, the legal status of nurses and private sector regulation.

Equations to estimate human milk intake in infants aged 7 to 10 months: prediction models from a cross-sectional study.

BACKGROUND: Obtaining valid estimates of nutrient intake in infants is currently limited by the difficulties of accurately measuring human milk intake. Current methods are either unsuitable for large-scale studies (i.e., the gold standard dose-to-mother stable isotope technique) or use set amounts, regardless of known variability in individual intake. OBJECTIVES: This cross-sectional study aimed to develop equations to predict human milk intake using simple measures and to carry out external validation of existing methods against the gold standard technique. METHODS: Data on human milk intake were obtained using the dose-to-mother stable isotope technique in 157 infants aged 7-10 mo and their mothers. Predictive equations were developed using questionnaire and anthropometric data (Model 1) and additional dietary data (Model 2) using lasso regression. Bland-Altman plots and intraclass correlation coefficients (ICC) also assessed the validity of existing methods (FITS and ALSPAC studies). RESULTS: The strongest univariate predictors of human milk intake in infants of 8.3 mo on average (46% female) were infant age, infant body mass index (BMI), number of breastfeeds a day, infant formula consumption, and energy from complementary food intake. Mean [95% confidence interval (CI)] differences in predicted versus measured human milk intake [mean (SD): 762 (257) mL/day] were 0.0 mL/day (-26, 26) for Model 1 (ICC 0.74) and 0.5 mL/day (-21, 22) for Model 2 (ICC 0.83). Corresponding differences were -197 mL/day (-233, -161; ICC 0.32) and -175 mL/day (-216, -134; ICC 0.41) for the methods used by FITS and ALSPAC, respectively. CONCLUSIONS: The Human Milk Intake Level Calculation provides substantial improvements on existing methods to estimate human milk intake in infants aged 7-10 mo, while utilizing data commonly collected in nutrition surveys. Although further validation in an external sample is recommended, these equations can be used to estimate human milk intake at this age with some confidence. This clinical trial was registered at http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=379436) as ACTRN12620000459921.

Quality of physical resources of health facilities in Indonesia: a panel study 1993-2007.

OBJECTIVE: The merits of mixed public and private health systems are debated. Although private providers have become increasingly important in the Indonesian health system, there is no comprehensive assessment of the quality of private facilities. This study examined the quality of physical resources of public and private facilities in Indonesia from 1993 to 2007. DESIGN AND SETTING: Data from the Indonesian Family Life Surveys in 1993, 1997, 2000 and 2007 were used to evaluate trends in the quality of physical resources for public and private facilities, stratified by urban/rural areas and Java-Bali/outer Java-Bali regions. MAIN OUTCOME MEASURES: The quality of six categories of resources was measured using an adapted MEASURE Evaluation framework. RESULTS: Overall quality was moderate, but higher in public than in private health facilities in all years regardless of the region. The higher proportion of nurses and midwives in private practice was a determinant of scope of services and facilities available. There was little improvement in quality of physical resources following decentralization. CONCLUSIONS: Despite significant increases in public investment in health between 2000 and 2006 and the potential benefits of decentralization (2001), the quality of both public and private health facilities in Indonesia did not improve significantly between 1993 and 2007. As consumers commonly believe the quality is better in private facilities and are increasingly using them, it is essential to improve quality in both private and public facilities. Implementation of minimum standards and effective partnerships with private practice are considered important.

High socioeconomic status is associated with stroke severity among stroke patients in the National Brain Centre Hospital, Jakarta, Indonesia.

Rapid economic growth has widened the gap between the rich and the poor, contributing to inequalities in socioeconomic status (SES) in Indonesia and possibly inequalities in health care. Here, we aimed to assess the potential association between SES and stroke severity in Indonesia, one of the largest low- and middle-income countries. Patients diagnosed with stroke at National Brain Centre (NBC) Hospital, Jakarta, Indonesia, in 2020 were included in the study. SES was measured based on marital status, occupation, education level, source of payment, and hospitalized class with smoking status and sex as confounder. Stroke severity was classified based on the National Institutes of Health Stroke Scale score into minor stroke (Adams et al., 1993, Amarenco et al., 2014, Andersen and Olsen, 2018, Austin and Steyerberg, 2017) and moderate to severe stroke (>4). A total of 2,443 patients with moderate to severe stroke (58%) were analyzed. Currently employed patients had a lower adjusted OR (aOR) of 0.65 (95% confidence interval [CI], 0.51-0.83) than unemployed patients. Patients with the highest education level, at least a diploma degree, had a lower aOR of 0.67 (95% CI, 0.49-0.92) than those with an elementary or no education. Our findings showed that patients with a higher SES had a lower risk of more severe stroke than those with a lower SES. Hence, we must focus on improving SES as part of stroke management.

Impact of milk secretor status on the fecal metabolome and microbiota of breastfed infants.

Maternal secretor status has been shown to be associated with the presence of specific fucosylated human milk oligosaccharides (HMOs), and the impact of maternal secretor status on infant gut microbiota measured through 16s sequencing has previously been reported. None of those studies have confirmed exclusive breastfeeding nor investigated the impact of maternal secretor status on gut microbial fermentation products. The present study focused on exclusively breastfed (EBF) Indonesian infants, with exclusive breastfeeding validated through the stable isotope deuterium oxide dose-to-mother (DTM) technique, and the impact of maternal secretor status on the infant fecal microbiome and metabolome. Maternal secretor status did not alter the within-community (alpha) diversity, between-community (beta) diversity, or the relative abundance of bacterial taxa at the genus level. However, infants fed milk from secretor (Se+) mothers exhibited a lower level of fecal succinate, amino acids and their derivatives, and a higher level of 1,2-propanediol when compared to infants fed milk from non-secretor (Se-) mothers. Interestingly, for infants consuming milk from Se+ mothers, there was a correlation between the relative abundance of Bifidobacterium and Streptococcus, and between each of these genera and fecal metabolites that was not observed in infants receiving milk from Se- mothers. Our findings indicate that the secretor status of the mother impacts the gut microbiome of the exclusively breastfed infant.

Effects of variations in atmospheric temperature and humidity on the estimation of exclusive breastfeeding status using the deuterium oxide dose-to-mother technique.

Background: The deuterium dose-to-mother (DTM) method measures the human milk intake of breastfed children. Recently, the use of this method has been expanded to classify babies objectively as exclusively breast fed (EBF) or not (non-EBF) based on quantification of non-milk oral water intake (NMOI). However, the calculation of NMOI estimates involves atmospheric temperature and humidity. Objective: To evaluate the effects of atmospheric temperature and humidity on NMOI calculation and the classification of exclusive breastfeeding. Methods: The effect of indoor temperature and relative humidity on NMOI and the estimated prevalence of non-EBF were examined in two existing data sets of DTM in children by varying temperature in the range of 15 to 35°C and relative humidity in the range of 20 to 80% representing the maximum span of indoor conditions expected. Population-level estimates of NMOI distributions were derived using the rstan package for R v2.21.2. Results: The NMOI decreased at a rate of -1.15 g/day per °C increase and at a rate of -1.01 g/day per percent increase in relative humidity; this was due to variations in non-oral water intake from the atmosphere, a component of the calculation of NMOI, which is dependent on temperature and humidity. For the various locations considered, the mean calculated NMOI varied between 24.6 and 53.3 g/day using the same input data. In the mixed-fed sample of babies, the prevalence of non-EBF based on the earlier defined NMOI cut-off of 86.6 g/day was reduced by 19% when relative humidity was increased by 60%. Conclusions: Atmospheric conditions are essential factors in the computation of NMOI, used in the objective classification of babies as exclusively breast fed or not, and should be considered when the DTM method is used to classify exclusive breastfeeding.

Epidemiologic, clinical, and serum markers may improve discrimination between bacterial and viral etiologies of childhood pneumonia.

Background: Discrimination of bacterial and viral etiologies of childhood community-acquired pneumonia (CAP) is often challenging. Unnecessary antibiotic administration exposes patients to undue risks and may engender antimicrobial resistance. This study aimed to develop a prediction model using epidemiological, clinical and laboratory data to differentiate between bacterial and viral CAP. Methods: Data from 155 children with confirmed bacterial or mixed bacterial and viral infection (N = 124) and viral infection (N = 31) were derived from a comprehensive assessment of causative pathogens [Partnerships for Enhanced Engagement in Research-Pneumonia in Pediatrics (PEER-PePPeS)] conducted in Indonesia. Epidemiologic, clinical and biomarker profiles (hematology and inflammatory markers) were compared between groups. The area under the receiver operating characteristic curve (AUROC) for varying biomarker levels was used to characterize performance and determine cut-off values for discrimination of bacterial and mixed CAP versus viral CAP. Diagnostic predictors of bacterial and mixed CAP were assessed by multivariate logistic regression. Results: Diarrhea was more frequently reported in bacterial and mixed CAP, while viral infections more frequently occurred during Indonesia's rainy season. White blood cell counts (WBC), absolute neutrophil counts (ANC), neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP), and procalcitonin (PCT) were significantly higher in bacterial and mixed cases. After adjusting for covariates, the following were the most important predictors of bacterial or mixed CAP: rainy season (aOR 0.26; 95% CI 0.08-0.90; p = 0.033), CRP ≥5.70 mg/L (aOR 4.71; 95% CI 1.18-18.74; p = 0.028), and presence of fever (aOR 5.26; 95% CI 1.07-25.91; p = 0.041). The model assessed had a low R-squared (Nagelkerke R2 = 0.490) but good calibration (p = 0.610 for Hosmer Lemeshow test). The combination of CRP and fever had moderate predictive value with sensitivity and specificity of 62.28 and 65.52%, respectively. Conclusion: Combining clinical and laboratory profiles is potentially valuable for discriminating bacterial and mixed from viral pediatric CAP and may guide antibiotic use. Further studies with a larger sample size should be performed to validate this model.

Chicken liver and eggshell crackers as a safe and affordable animal source food for overcoming micronutrient deficits during pregnancy and lactation in Indonesia: a double-blind, randomised placebo-controlled trial (SISTIK Growth Study).

Background: Indonesia ranks fifth in terms of the number of stunted children and there has been little change in the stunting prevalence in the last decade. In earlier observational studies conducted in 2014-2015, we identified several key underlying problems with the potential to impact stunting in Sumedang district, West Java, Indonesia. Deficits in intakes of growth-limiting micronutrients were observed, most notably calcium, iron, zinc, and vitamin A, emphasizing the need for a food-based intervention to overcome these micronutrient deficits in the diets of mothers and their infants. Methods: A double-blind placebo-controlled cluster randomised trial comparing the effect of daily consumption of 75 grams of locally produced micronutrient-enriched crackers (MEC) (intervention group) compared to placebo crackers (control group) by mothers at two-time intervals: (i) from the 8-14 weeks of pregnancy to delivery (i.e., 28-34 weeks of consumption of MEC) on birth length, and (ii) from the 8-14 weeks of pregnancy to 5 months post-partum on attained linear growth and linear growth velocity of breast-fed infants. A total of 324 pregnant women from 28 clusters (villages) located in 3 sub-districts in Sumedang district, West Java, Indonesia, will be randomly assigned to either intervention (n=14 villages) or control (n=14 villages). Discussi on: This will be the first study in Indonesia to use crackers based on powdered eggshells and chicken liver, in a form which is acceptable, safe, and has a long shelf life. If daily consumption of MEC for 6 months during pregnancy can enhance birth length, or their continued daily consumption for 5 months postpartum improves both attained and incremental linear growth at 5 months of age, then scaling-up in Indonesia may be considered. Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04564222 ; 25 th September 2020.

Characteristics of Drug-sensitive and Drug-resistant Tuberculosis Cases among Adults at Tuberculosis Referral Hospitals in Indonesia.

As Indonesia's rifampin resistance testing rates are lower than global testing rates per the 2020 WHO global tuberculosis (TB) report, prevalence of multidrug-resistant TB may be underestimated. Our study aimed to evaluate prevalence and patterns of TB drug resistance (DR) within Indonesia. We conducted a cross-sectional analysis of baseline data collected from 2017-2018 as part of a cohort study of adults with presumed pulmonary TB at 7 DR-TB referral hospitals in Indonesia. Bacteriological examinations (acid-fast bacilli, GeneXpert, sputum culture) and drug-susceptibility testing were performed following the guidelines of the National TB Program. Of 447 participants with complete bacteriological examinations, 312 (69.8%) had positive sputum cultures for Mycobacterium tuberculosis. The proportion of MDR and pre-extensively drug-resistant was higher in previously treated compared with newly diagnosed participants (52.5% [73/139] versus 15% [26/173]). Compared with drug-sensitive case, drug-resistant TB was associated with cavities. Given the difference between rates of DR in TB referral hospitals from our study compared with the WHO survey in 2019 that showed 17.7% and 3.3% DR among previously treated and newly diagnosed participants globally, further characterization of Indonesia's TB epidemiology in the general population is needed. Strategies, including public policies to optimize case finding, strengthen capacity for resistance testing, and prevent loss to follow-up will be critical to reduce the burden of TB in Indonesia.

Performance of Xpert MTB/RIF and sputum microscopy compared to sputum culture for diagnosis of tuberculosis in seven hospitals in Indonesia.

Introduction: Tuberculosis (TB) is a major public health concern in Indonesia, where the incidence was 301 cases per 100,000 inhabitants in 2020 and the prevalence of multi-drug resistant (MDR) TB is increasing. Diagnostic testing approaches vary across Indonesia due to resource limitations. Acid-fast bacilli (AFB) smear is widely used, though Xpert MTB/RIF has been the preferred assay for detecting TB and rifampicin resistance since 2012 due to higher sensitivity and ability to rapidly identify rifampicin resistance. However, <1,000 Xpert instruments were available in Indonesia as of 2020 and the Xpert supply chain has suffered interruptions. Methods: We compared the performance of Xpert MTB/RIF and AFB smear to facilitate optimization of TB case identification. We analyzed baseline data from a cohort study of adults with pulmonary TB conducted at seven hospitals across Indonesia. We evaluated sensitivity and specificity of AFB smear and Xpert MTB/RIF using Mycobacterium tuberculosis (Mtb) culture as the gold standard, factors associated with assay results, and consistency of Xpert MTB/RIF with drug susceptibility test (DST) in detecting rifampicin resistance. Results: Sensitivity of AFB smear was significantly lower than Xpert MTB/RIF (86.2 vs. 97.4%, p-value <0.001), but specificity was significantly better (86.7 vs. 73.3%, p-value <0.001). Performance varied by hospital. Positivity rate for AFB smear and Mtb culture was higher in subjects with pulmonary cavities and in morning sputum samples. Consistency of Xpert MTB/RIF with DST was lower in those with rifampicin- sensitive TB by DST. Discussion: Additional evaluation using sputa from primary and secondary Indonesian health centers will increase the generalizability of the assessment of AFB smear and Xpert MTB/RIF performance, and better inform health policy. Clinical trial registration: [https://clinicaltrials.gov/], identifier [NCT027 58236].

The characteristics of bacteremia among patients with acute febrile illness requiring hospitalization in Indonesia.

Blood culturing remains the "gold standard" for bloodstream infection (BSI) diagnosis, but the method is inaccessible to many developing countries due to high costs and insufficient resources. To better understand the utility of blood cultures among patients in Indonesia, a country where blood cultures are not routinely performed, we evaluated data from a previous cohort study that included blood cultures for all participants. An acute febrile illness study was conducted from July 2013 to June 2016 at eight major hospitals in seven provincial capitals in Indonesia. All participants presented with a fever, and two-sided aerobic blood cultures were performed within 48 hours of hospital admission. Positive cultures were further assessed for antimicrobial resistance (AMR) patterns. Specimens from participants with negative culture results were screened by advanced molecular and serological methods for evidence of causal pathogens. Blood cultures were performed for 1,459 of 1,464 participants, and the 70.6% (1,030) participants that were negative by dengue NS1 antigen test were included in further analysis. Bacteremia was observed in 8.9% (92) participants, with the most frequent pathogens being Salmonella enterica serovar Typhi (41) and Paratyphi A (10), Escherichia coli (14), and Staphylococcus aureus (10). Two S. Paratyphi A cases had evidence of AMR, and several E. coli cases were multidrug resistant (42.9%, 6/14) or monoresistant (14.3%, 2/14). Culture contamination was observed in 3.6% (37) cases. Molecular and serological assays identified etiological agents in participants having negative cultures, with 23.1% to 90% of cases being missed by blood cultures. Blood cultures are a valuable diagnostic tool for hospitalized patients presenting with fever. In Indonesia, pre-screening patients for the most common viral infections, such as dengue, influenza, and chikungunya viruses, would maximize the benefit to the patient while also conserving resources. Blood cultures should also be supplemented with advanced laboratory tests when available.

Qualitative and quantitative vibrational spectroscopic analysis of macronutrients in breast milk.

Raman and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy were used to analyze 208 breast milk samples as part of a larger research study. Comprehensive qualitative and quantitative analysis was carried out using chemometric methods: principal component analysis (PCA) and partial least squares (PLS) regression. The obtained information on the main macronutrients (protein, fat and carbohydrate) were primarily evaluated in relation to the available metadata of the samples, where study location and respective primary food sources revealed a stronger differentiation in fat composition than its absolute content. The limitations and challenges of using both spectroscopic techniques for the type of analysis are also highlighted.

Determination of modifiable risk factors for length-for-age z-scores among resource-poor Indonesian infants.

To reduce the burden of early-life linear growth faltering in low- and middle-income countries, interventions have focused on nutrition strategies, sometimes combined with water quality, sanitation, and hygiene (WASH). However, even when combined, their effects on linear growth have been inconsistent. Here, we investigate potential predictors of length-for-age z-scores (LAZ) in a cohort of resource-poor rural Indonesian infants to inform the optimal strategies to reduce linear growth faltering. Apparently healthy rural breastfed Indonesian infants were randomly selected from birth registries at age 6 months (n = 230) and followed up at 9 (n = 202) and 12 (n = 190) months. Using maximum likelihood estimation, we examined longitudinal relationships among socio-demographic status, maternal height, infant sex, age, water source, sanitation facility, energy, protein, micronutrient intakes and biomarkers (serum ferritin, zinc, retinol binding protein (RBP), selenium-adjusted for inflammation), and α-1-acid glycoprotein (AGP) and C-reactive protein (CRP) (systemic inflammation biomarkers) at age 6 and 9 months on LAZ at age 9 and 12 months. Stunting (LAZ <-2) at 6, 9, and 12 months was 15.7%, 19.3%, and 22.6%, respectively. In the full model, the predictor variable at age 6 months that was most strongly associated with infant LAZ at 9 months was maternal height (0.18 (95% CI 0.03, 0.32) SD). At age 9 months, the strongest predictors of LAZ at 12 months were improved drinking water source (-0.40 (95% CI -0.65, -0.14) vs. not improved), elevated AGP compared to not elevated (0.26 (95%CI -0.06, 0.58), maternal height (0.16 (95% CI 0.02, 0.31) SD), sex (0.22 (95% CI -0.02,0.45) female vs. male), serum RBP (0.12 (95% CI -0.01, 0.25) SD), and protein intake (0.17 (95% CI -0.01, 0.35) SD). Health promotion that includes exclusive breastfeeding up to the first six months and follows microbial water quality guidelines to ensure water intake is always safe should be considered.