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Background In previous studies, researchers have identified systemic lupus erythematosus (SLE) as a risk factor for tuberculosis (TB), but data from TB-endemic countries are still relatively scarce. We examined TB in a large cohort of SLE patients in Indonesia. Methods All patients registered in a lupus registry of the top referral hospital for West Java between 2008 and 2020 were included. Data on SLE characteristics and treatment were retrieved from the registry, and data on TB diagnosis, localization, and outcome were extracted from medical records. Cox-proportional hazard model was used to examine risk factors for development of TB. Results Among 1278 SLE patients observed over a total of 4804 patient-years, 131 patients experienced 138 episodes of TB, a median of 2 years (interquartile range, 0.6–5.4) after diagnosis of SLE. A total of 113 patients (81.9%) had pulmonary involvement and 61 (44.2%) had extrapulmonary involvement, with disseminated disease in 26 of 138 episodes (18.8%), and 13 of 131 patients (9.9%) died from TB. The estimated TB incidence was 2873 cases per 100 000 person years. In multivariate cox regression analysis, development of TB was associated with household TB contact (hazard ratio [HR], 7.20; 95% confidence interval [CI], 4.05–12.80), pulse methylprednisolone therapy (HR, 1.64; 95% CI, 1.01–2.67), and age ≤25 years old at SLE diagnosis (HR, 1.54; 95% CI, 1.00–2.35). Conclusions There is a high burden of TB in SLE patients in this TB-endemic setting, underlining the need for evaluation or implementation of TB preventive strategies. [ABSTRACT FROM AUTHOR]

The article presents a case study of Lower Bacillus Calmette-Guerin Protection against Mycobacterium tuberculosis. This cohort study followed IFN-g release assay (IGRA)-negative TB case contacts of patients older than 5 years with sputum smear-positive TB in the INFECT(Innate Factors in Early Clearance of Mycobacterium Tuberculosis) study; and Index case characteristics were recorded and their M. tuberculosis isolates obtained.

Background: Early clearance of Mycobacterium tuberculosis is the eradication of infection before an adaptive immune response develops. We aimed to identify host factors associated with early clearance.Methods: Indonesian household contacts patients with smear-positive tuberculosis (TB) had an interferon-γ release assay (IGRA) at baseline and 14 weeks later. Early clearance was defined as a persistently negative IGRA. Contact characteristics, exposure, and disease phenotype were assessed for association with a positive IGRA at each time point.Results: Of 1347 contacts of 462 TB cases, 780 (57.9%) were IGRA positive and 490 (36.3%) were IGRA negative. After 14 weeks, 116 of 445 (26.1%) initially negative contacts were IGRA converters; 317 (71.2%) remained persistently negative. BCG vaccination reduced the risk of a positive baseline IGRA (relative risk [RR], 0.89 [95% confidence interval {CI} .83-.97]; P = .01), and strongly reduced the risk of IGRA conversion (RR, 0.56 [95% CI, .40-.77]; P < .001). BCG protection decreased with increasing exposure (P = .05) and increasing age (P = .004). Risk of IGRA conversion was positively associated with hemoglobin concentration (P = .04).Conclusions: A quarter of household TB case contacts were early clearers. Protection against M. tuberculosis infection was strongly associated with BCG vaccination. Lower protection from BCG with increasing M. tuberculosis exposure and age can inform vaccine development. [ABSTRACT FROM AUTHOR]

Background: The epidemiology of acute febrile illness, a common cause of hospitalization in Indonesia, has not been systematically studied. Methodology/Principal gindings: This prospective observational study enrolled febrile patients (temperature ≥38°C) aged ≥1 year from July 2013 until June 2016 at eight government referral teaching hospitals in seven provincial capitals in Indonesia. Patients were managed according to the hospital standard-of-care (SOC), and blood samples were drawn for molecular and serological assays. Clinical data, laboratory results, and specimens for additional tests were collected at enrollment, days 14–28, and at three months. Regular follow-up visits were then scheduled for every three months either until symptoms resolved or until one year. In total, this study included 1,486 adult and pediatric patients presenting with multi-organ (768, 51.7%), gastrointestinal (497, 33.0%), respiratory (114, 7.7%), constitutional (62, 4.2%), skin and soft-tissue (24, 1.6%), central nervous system (17, 1.1%), or genitourinary (4, 0.3%) manifestations. Microbiological diagnoses were found in 1,003/1,486 (67.5%) participants, of which 351/1,003 (35.0%) were not diagnosed during hospitalization using SOC diagnostic tests. Missed diagnoses included all cases caused by Rickettsia spp., chikungunya, influenza, and Seoul virus. The most common etiologic agents identified were dengue virus (467, 46.6%), Salmonella spp. (103, 10.3%), and Rickettsia spp. (103, 10.3%). The overall mortality was 89 (5.9%). Conclusions/Significance: Febrile illness in Indonesia has various microbiologic etiologies and substantial overall mortality. Diagnostic limitations and lack of epidemiologic data resulted in potentially treatable, and at times fatal, diseases being missed. Author summary: In tropical countries like Indonesia, fever due to infectious disease is the most common reason for hospitalization. However, diagnoses are mostly unconfirmed, as diagnostic tests are not available or are not performed due to budget constraints. Consequently, many patients are only treated based on clinical syndromes. To gain a better understanding of the epidemiology of acute fever in Indonesia, we conducted a study at eight hospitals in the seven largest cities from 2013–2016. We enrolled 1,486 subjects aged ≥1 year with acute fever ≥38°C. Blood cultures were mandatory for all subjects, while cultures of other biological specimens, microscopic examinations, and rapid tests for specific pathogens were based on clinical judgment and availability. Retrospectively, we performed molecular and serological testing for a panel of bacterial and viral pathogens for systemic, respiratory, and diarrheal diseases. We found six pathogens to be the most prevalent: dengue virus (47%), Salmonella Typhi/Paratyphi (10%), Rickettsia typhi (10%), influenza virus (7%), Leptospira spp. (5%), and chikungunya virus (4%). Rickettsia typhi, influenza, and chikungunya had not been considered in the differential diagnosis of any subject at the hospitals. Thus, multiple pathogens were associated with acute febrile illnesses, and a subset of treatable cases were missed. This may have resulted in increased overall mortality. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) infection is a major cause of acute febrile illness in Indonesia. Diagnostic inaccuracy may occur due to its varied and non-specific presentation. Characterization of DENV epidemiology, clinical presentation, and virology will facilitate appropriate clinical management and public health policy. A multicenter observational cohort study was conducted in Indonesia to assess causes of acute fever requiring hospitalization. Clinical information and specimens were collected at enrollment, 14–28 days, and 3 months from 1,486 children and adults. Total of 468 (31.9%) cases of DENV infection were confirmed by reference laboratory assays. Of these, 414 (88.5%) were accurately diagnosed and 54 had been misdiagnosed as another infection by sites. One hundred initially suspected dengue cases were finally classified as 'non-dengue'; other pathogens were identified in 58 of those cases. Mortality of DENV infection was low (0.6%). Prior DENV exposure was found in 92.3% of subjects >12 years. DENV circulated year-round in all cities, with higher incidence from January to March. DENV-3 and DENV-1 were the predominant serotypes. This study identified DENV-1 with TS119(C→T) substitution in the serotyping primer annealing site, leading to failure of serotype determination. DENV is a common etiology of acute febrile illness requiring hospitalization in Indonesia. Diagnostic accuracy at clinical sites merits optimization since misdiagnosis of DENV infection and over-estimation of dengue can negatively impact management and outcomes. Mutation at the annealing site of the serotyping primer may confound diagnosis. Clinicians should consider following diagnostic algorithms that include DENV confirmatory testing. Policy-makers should prioritize development of laboratory capacity for diagnosis of DENV. Dengue is a mosquito-borne viral disease whose global incidence has increased dramatically in recent decades. Infection with any of the four serotypes can cause subclinical to life-threatening illness. Indonesia and other subtropical regions are hyper-endemic, thus are at increased risk of disease impact. We conducted a multicenter observational cohort study of acute febrile illness requiring hospitalization in children and adults in Indonesia from 2013–2016. Epidemiology, clinical course, and virology of dengue were assessed. Dengue infection is the main cause of hospitalized acute febrile illness in Indonesia. DENV serotypes 1–4 circulated throughout the study period, with highest overall rates in January to March. We observed DENV-1 with TS119(C→T) substitution in the serotyping primer annealing site that caused failure of routine detection. Diagnostic accuracy at clinical sites merits optimization. Clinicians should consider following diagnostic algorithms that include DENV confirmatory testing, while policy-makers should prioritize development of laboratory capacity for diagnosis of DENV. [ABSTRACT FROM AUTHOR]

Background: Little is known about HIV treatment outcomes in Indonesia, which has one of the most rapidly growing HIV epidemics worldwide. Methods: We examined possible differences in loss to follow-up (LTFU) and survival between HIV-infected females and males over a 7-year period in an HIV clinic in Bandung, West Java. Data imputation was performed on missing covariates and a multi-state Cox regression was used to investigate the effects of sex and other covariates on patient transitions among four states: (1) clinic enrollment with HIV, (2) initiation/continuation/re-initiation of antiretroviral therapy (ART), (3) LTFU, and (4) death. Results: We followed 3215 patients (33% females), for a total of 8430 person-years. ART was used by 59% of patients at some point. One-year retention was 73% for females and 77% for males (p = 0.06). One-year survival was 98% for both females and males (p = 0.15). Females experienced a higher relative hazard to transition from HIV to LTFU (adjusted hazard ratio 1.21; 95% confidence interval 1.00–1.45), but this decreased after adjustments for clinical variables (aHR 0.94; 95% CI 0.79–1.11). Similarly, a lower relative hazard in females to transition from ART to death (aHR 0.59; 95% CI 0.35–0.99) decreased after adjustments for demographic variables. Conclusion: This Indonesian cohort has low ART uptake and poor overall pre- and post-ART retention. Female-male differences in survival and retention were gone after adjusting for clinical and sociodemographic factors such as CD4 count and education level. Efforts should be made to improve retention among patients with lower education. [ABSTRACT FROM AUTHOR]

Treatment of multidrug-resistant tuberculosis (MDR-TB) with second-line injectable drugs may result in an electrolyte imbalance. This retrospective study was performed to compare and evaluate the effect of kanamycin and capreomycin on serum potassium, calcium, and magnesium in the first and second month treatment at a tertiary, top-referral hospital in Bandung, Indonesia. Data from 84 subjects with complete medical records of at least serum potassium during either kanamycin-based or capreomycin-based treatment were retrieved from the institutional database. Among these, 53 subjects had complete serum calcium data and 53 subjects had complete serum magnesium data. After the first month of MDR-TB treatment, there was a significant decrease in mean serum potassium (4.0 ± 0.4 mEq/L to 3.7 ± 0.5 mEq/L, p<0.003) in the kanamycin-based group and (4.1 ± 0.5 mEq/L to 3.2 ± 0.6 mEq/L, p<0.001) in the capreomycin-based group. Serum potassium levels were significantly lower in the capreomycin-based group than in the kanamycin-based group (3.2 ± 0.6 mEq/L vs 3.7 ± 0.5 mEq/L, p<0.001). The incidence of hospitalization and requirement for a change in the treatment regimen due to electrolyte imbalances were higher in the capreomycin-based group. No previous longitudinal study has evaluated serum potassium, magnesium, and calcium from the first month of MDR-TB treatment with either kanamycin-based or capreomycin-based regimens. Our findings emphasize the importance of routine monitoring of serum potassium, magnesium, and calcium during MDR-TB treatment, and that more attention should be paid when treatment is given using the capreomycin-based regimen. Moreover, our study supported the 2018 World Health Organization treatment guideline recommendations for removal of kanamycin and capreomycin from the MDR-TB regimens. [ABSTRACT FROM AUTHOR]

Background and Objectives: Intrauterine growth retardation (IUGR) is related to mortality and morbidity. However, defining IUGR by suitable field methods remains a challenge. A maternal-child Risk-Approach-Strategy (during 1988-1989) and follow-on Tanjungsari Cohort Study (TCS) (1989-1990), aimed to generate a practical classification of IUGR and explore its usage in predicting growth, mortality and morbidity of infants in the cohort. Study Design: Some 3892 singleton live-birth infants were followed. IUGR was defined by birth weight (BW) and length (BL) classified as: acute, chronic, non-IUGR or 'probably preterm'. Growth, mortality, and survival curve were calculated to prove that the classification identified the most vulnerable infants. Fever >3 days and diarrhoea were assessed based on IUGR classification, sex, exclusive breastfeeding, and environmental factors. Results: IUGR infant weight and length did not catch-up with the non-IUGR in the first year. Infant mortality rate was 44.7 per 1000 where some 61% died within 90 days. Using age specific mortality by BW, 23.6% of all deaths occurred when it was <2500 g compared to 66.2% from IUGR and preterm groups. Fever and diarrhoea rates increased over 12 months. Diarrhoea was associated with poor source-of-drinking-water and latrine. Conclusion: The IUGR classification predicted one-year growth curves and survival, besides age and sex. IUGR based on BW and BL identified a larger group of at-risk infants than did low BW. High morbidity rates were partly explained by poor environmental conditions. IUGR inclusive of BL has value in optimizing nutritional status in the first 1000 days of life. [ABSTRACT FROM AUTHOR]

Background: Male injecting drug users drove the onset of the HIV epidemic in Indonesia but over time more women have been diagnosed. We examined the relative proportion of female patients in an HIV cohort and characterized their probable transmission route and reproductive profile. Designs: Prospective cohort study in a referral hospital in West Java. Methods: Interviews with standardized questionnaires, physical and laboratory examinations were done for 2622 individuals enrolled in HIV care between 2007 and 2012. The proportion of women in this cohort was compared with national estimates. The general characteristics of HIV-infected women and men as well as the sexual and reproductive health of HIV-infected women were described. Results: The proportion of female patients enrolled in HIV care increased from 22.2 % in 2007 to 38.3 % in 2012, in line with national estimates. Women were younger than men, fewer reported a history of IDU (16.1 vs. 73.8 %, p < 0.001) and more were tested for HIV because of a positive partner (25.5 vs. 4.0 %, p < 0.001). The majority of women were in their reproductive age, had children, and were not using contraceptives at the time of enrolment. Conclusion: HIV-infected women in Indonesia have specific characteristics that differ them from women in the general population. Further research to elucidate the characteristics of women exposed to HIV, their access to testing and care and sexual and reproductive needs can help reduce transmission to women and children in the context of concentrated HIV epidemic in Indonesia. [ABSTRACT FROM AUTHOR]

The correct Funding statement is as follows: This project has been funded in whole or in part with MOH Indonesia and Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, under contract Nos. Reference 1 Gasem MH, Kosasih H, Tjitra E, Alisjahbana B, Karyana M, Lokida D, et al. (2020) An observational prospective cohort study of the epidemiology of hospitalized patients with acute febrile illness in Indonesia. [Extracted from the article]

Background: It remains unclear whether the natural course of human immunodeficiency virus (HIV) differs in subjects infected through injecting drug use (IDU) and no data have been published from low- or middle-income countries. We addressed this question in an urban cohort in Indonesia, which is experiencing a rapidly growing HIV epidemic strongly driven by IDU. Methods: All antiretroviral treatment (ART) naïve HIV-positive patients who had at least two subsequent CD4 cell counts available before starting ART were included in this study.We examined the association between IDU and CD4 cell decline using a linear mixed model, with adjustment for possible confounders such as HIV viral load and hepatitis C antibodies. Results: Among 284 HIV-positive ART naïve patients, the majority were male (56%) with a history of IDU (79% among men). People with a history of IDU had a statistically significant faster decline in CD4 cells (pB0.001). Based on our data, patients with a history of IDU would have an average 33% decline in CD4 cells after one year without ART, compared with a 22% decline among non-users. At two years, the decline would average 66 and 40%, respectively. No other factor was significantly associated with CD4 cell decline. Conclusions: We show that a history of IDU is associated with a more rapid CD4 cell natural decline among HIV-positive individuals in Indonesia. These findings have implications for monitoring ART naïve patients with a history of IDU and for starting ART in this group. [ABSTRACT FROM AUTHOR]

Background: Distortion of iron homeostasis may contribute to the pathogenesis of human immunodeficiency virus (HIV) infection and tuberculosis (TB). We studied the association of the central iron-regulatory hormone hepcidin with the severity of HIV and the association between hepcidin and other markers of iron homeostasis with development of TB. Methods: Three groups of patients were selected from a prospective cohort of HIV-infected subjects in Bandung, Indonesia. The first group consisted of HIV-infected patients who started TB treatment more than 30 days after cohort enrollment (cases). The second group consisted of HIV-infected patients who were matched for age, gender and CD4 cell count to the cases group (matched controls). The third group consisted of HIV-infected patients with CD4 cell counts above 200 cells/mm3 (unmatched controls). Iron parameters including hepcidin were compared using samples collected at cohort enrollment, and compared with recently published reference values for serum hepcidin. Results: A total of 127 HIV-infected patients were included, 42 cases together with 42 matched controls and 43 unmatched controls. Patients with advanced HIV infection had elevated serum hepcidin and ferritin levels. Hepcidin levels correlated inversely with CD4 cells and hemoglobin. Cases had significantly higher hepcidin and ferritin concentrations at cohort enrollment compared to matched controls, but these differences were fully accounted for by the cases who started TB treatment between day 31 and 60 after enrollment. Hepcidin levels were not different in those with or without hepatitis C infection. Conclusion: Iron metabolism is distorted in advanced HIV infection with CD4 cell counts correlating inversely with serum hepcidin levels. High serum hepcidin levels and hyperferritinemia were found in patients starting TB treatment shortly after cohort enrollment, suggesting that these parameters have a predictive value for development of manifest TB in HIV-infected patients. [ABSTRACT FROM AUTHOR]

Animal studies have shown that the globally emerging Beijing genotype strains of Mycobacterium tuberculosis are more virulent than other strains. We examined whether Beijing strains increase treatment failure in a prospective cohort study in Indonesia. Among 818 tuberculosis cases, positive sputum culture results after 6 months of treatment were more common among patients infected with Beijing strains (33.4%) than among those infected with non-Beijing strains (relative risk, 1.94 [95% confidence interval, 1.26-3.00]), even after adjustment for differences in drug resistance. These data suggest that M. tuberculosis Beijing genotype strains have a higher capacity to withstand tuberculosis treatment, even in the absence of drug resistance. [ABSTRACT FROM AUTHOR]

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