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Background: No gold standard diagnostic test exists for latent tuberculosis infection (LTBI). The intra-dermal tuberculin skin test (TST) has known limitations and Interferon-gamma release assays (IGRA) have been developed as an alternative. We aimed to assess agreement between IGRA and TST, and risk factors for test positivity, in Indonesian healthcare students. Methods: Medical and nursing students starting their clinical training were screened using IGRA and TST. Agreement between the two tests was measured using Cohen's Kappa coefficient. Logistic regression was used to identify factors associated with test positivity. Results: Of 266 students, 43 (16.2%) were IGRA positive and 85 (31.9%) TST positive. Agreement between the two tests was 74.7% (kappa 0.33, 95% CI 0.21–0.45, P<0.0001). Students who had direct contact with family or friends with TB were less likely to be test positive using IGRA (AOR 0.18, 95% CI 0.05–0.64) and using TST (AOR 0.51, 95% CI 0.26–0.99). Conclusion: Test positivity for LTBI was lower when measured by IGRA than by TST, with poor agreement between the two tests. Known close TB contact was unexpectedly negatively associated with positivity by either test. Longitudinal studies may be required to help determine the best test for LTBI in healthcare students in Indonesia. [ABSTRACT FROM AUTHOR]

Background: Indonesia has the second highest incidence of tuberculosis in the world. While 74% of people with tuberculosis in Indonesia first accessed the private health sector when seeking care for their symptoms, only 18% of tuberculosis notifications originate in the private sector. Little is known about the impact of the COVID-19 pandemic on the private sector. Using unannounced standardized patient visits to private providers, we aimed to measure quality of tuberculosis care during the COVID-19 pandemic. Methods: A cross-sectional study was conducted using standardized patients in Bandung City, West Java, Indonesia. Ten standardized patients completed 292 visits with private providers between 9 July 2021 and 21 January 2022, wherein standardized patients presented a presumptive tuberculosis case. Results were compared to standardized patients surveys conducted in the same geographical area before the onset of COVID-19. Results: Overall, 35% (95% confidence interval (CI): 29.2–40.4%) of visits were managed correctly according to national tuberculosis guidelines. There were no significant differences in the clinical management of presumptive tuberculosis patients before and during the COVID-19 pandemic, apart from an increase in temperature checks (adjusted odds ratio (aOR): 8.05, 95% CI: 2.96–21.9, p < 0.001) and a decrease in throat examinations (aOR 0.16, 95% CI: 0.06–0.41, p = 0.002) conducted during the pandemic. Conclusions: Results indicate that providers successfully identify tuberculosis in their patients yet do not manage them according to national guidelines. There were no major changes found in quality of tuberculosis care due to the COVID-19 pandemic. As tuberculosis notifications have declined in Indonesia due to the COVID-19 pandemic, there remains an urgent need to increase private provider engagement in Indonesia and improve quality of care. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) viral infections are critical causes of morbidity and mortality in children; however, comprehensive data on etiology is lacking in developing countries such as Indonesia. To study the etiology of CNS infections in a pediatric population, 50 children admitted to two hospitals in Bandung, West Java, during 2017–2018 were enrolled in a CNS infection study. Cerebrospinal fluid and serum specimens were tested using molecular, serological, and virus isolation platforms for a number of viral and bacteriological agents. Causal pathogens were identified in 10 out of 50 (20%) and included cytomegalovirus (n = 4), Streptococcus pneumoniae (n = 2), tuberculosis (n = 2), Salmonella serotype Typhi (n = 1) and dengue virus (n = 1). Our study highlights the importance of using a wide range of molecular and serological detection methods to identify CNS pathogens, as well as the challenges of establishing the etiology of CNS infections in pediatric populations of countries with limited laboratory capacity. Author summary: Pediatric CNS infection is a high burden for public health in many developing countries including Indonesia where diagnostic capacity is limited. In this study we identify the clinical characteristics and etiology of CNS infection in 50 pediatric population from two hospitals in Indonesia. The data identified cytomegalovirus, dengue, Salmonella Typhi, Streptococcus pneumoniae and Mycobacterium tuberculosis as the etiology of infection while 80% of cases remain unidentified. The results are expected to raise awareness for policy makers to improve management and laboratory diagnosis of CNS infection in children. Further studies are required to identify contributing factors to the burden of CNS infection. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is associated with higher severity and mortality in SARS-CoV-2 infections. Vaccination has been encouraged to boost immunity and prevent these unfortunate outcomes. Few studies have evaluated antibody levels after COVID-19 vaccination in patients with T2DM. Therefore, we examined the vaccination status and anti-SARS-CoV-2 antibody levels to identify the factors that affect the antibody levels in patients with T2DM. This cross-sectional study was conducted at the Dr. Hasan Sadikin Hospital and Bandung Kiwari Hospital, Bandung, West Java, Indonesia, between October and November 2022. Adult participants with and without T2DM were tested for SARS-CoV-2 antibodies using a point-of-care quantitative immunochromatographic assay. We enrolled 289 participants: 201 participants with T2DM and 88 participants without T2DM. The T2DM participants had a lower vaccination rate compared with the non-T2DM participants. However, no significant differences in antibody levels were observed between the two groups. Higher antibody levels among the T2DM participants were associated with mRNA vaccination and a history of COVID-19 illness. The lower antibody response observed among the T2DM participants with chronic obstructive pulmonary disease suggests that such patients may need antibody level measurement and an additional booster vaccine. [ABSTRACT FROM AUTHOR]

Murine typhus (MT), an infection caused by the gram-negative bacteria Rickettsia typhi (R. typhi), is a significant cause of acute febrile illness (AFI) in Southeast Asia but is rarely reported in Indonesia. The current study aimed to describe the clinical characteristics of MT cases in Bandung, West Java. Non-confirmed AFI cases (n = 176) from a prospective cohort study of whom paired serum samples (acute (T1), midterm (T2), or convalescent (T3)) were available were screened using MT serology. IgG against R. typhi was detected in the T2 or T3 samples using an in-house ELISA. Positive IgG samples were further screened for the presence of IgM. If both IgM and IgG were positive, the endpoint titer of T1, T2, or T3 was determined. In cases with a fourfold increase in titer, real-time PCR of T1 samples was performed to detect R. typhi DNA. In total, 71/176 (40.3%) patients tested positive for IgG antibody, and 26 AFI cases were confirmed as MT (23 cases by PCR, 3 cases by fourfold titer increased IgG or IgM titer). The most common clinical symptoms in the confirmed cases were headache (80%), arthralgia (73%), malaise (69%), and myalgia (54%). In these cases, the presumptive clinical diagnoses were typhoid fever (43.2%), dengue (38.5%), and leptospirosis (19.2%). MT was not considered in any of the patients, and no patients received doxycycline. These findings confirmed that MT is an important cause of AFI in Indonesia. MT should be included in the differential diagnosis of AFI, and empirical treatment with doxycycline should be considered. [ABSTRACT FROM AUTHOR]

Immune system dysregulation in people with diabetes mellitus (DM) increases the risk of acquiring severe infection. We compared the clinical characteristics and laboratory parameters of coronavirus disease 2019 (COVID-19) patients with and without DM and estimated the effect of DM on mortality among COVID-19 patients. A retrospective cohort study collecting patients' demographic, clinical characteristics, laboratory parameters and treatment outcomes from medical records was conducted in a hospital in Bandung City from March to December 2020. Univariable and multivariable logistic regression was performed to determine the association between DM and death. A total of 664 COVID-19 patients with positive real-time reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 were included in this study, of whom 147 were with DM. Half of DM patients presented HbA1c ≥10%. DM patients were more likely to present with comorbidities and severe to critical conditions at admission (P <0.001). Laboratory parameters such as neutrophil-lymphocyte count ratio, C-reactive protein, D-dimer, ferritin, and lactate dehydrogenase were higher in the DM group. In the univariate analysis, variables associated with death were COVID-19 severity at baseline, neurologic disease, DM, age ≥60 years, hypertension, cardiovascular disease, and chronic kidney disease. DM remained associated with death (aOR 1.82; 95% CI 1.13–2.93) after adjustment with sex, age, hypertension, cardiovascular disease, and chronic kidney disease. In conclusion, COVID-19 patients with DM are more likely to present with a very high HbA1c, comorbidities, and severe-critical illness. Chronic inflammation in DM patients may be aggravated by the disruption of immune response caused by COVID-19, leading to worse laboratory results and poor outcomes. [ABSTRACT FROM AUTHOR]

Background: During COVID-19 pandemic, it is difficult to distinguish febrile patient infected by SARS-CoV-2 or bacterial causes. Howell-Jolly bodies are a well-known entity found in red blood cells. They are nuclear fragments, composed of deoxyribonucleic acid, commonly observed in the peripheral blood smears of hyposplenic or asplenic patients. Recently, similar inclusions often referred to as Howell-Jolly body-like inclusions (HJBLIs) have been reported in the neutrophils of patients with acquired immune deficiency syndrome (AIDS) and COVID-19 patient. Aim: To explore whether HJBLIs in peripheral blood smear could differentiate between patients with confirmed SARS-CoV-2 and bacterial pneumonia. Methods: We performed cross-sectional study using secondary data from COVID-19 database and re-evaluated peripheral blood smears to identify HJBLIs. We included confirmed COVID-19 adults age 18 years who were hospitalized in Dr. Hasan Sadikin General Hospital, Bandung, Indonesia from March 1st 2020–May 31st 2020. We also examined peripheral blood smears in patients with confirmed bacterial pneumonia as a control group. Clinical characteristics including disease severity, CURB-65 score, comorbidity, and the present of HJBLIs in peripheral blood smears were evaluated. Results: Overall, 33 patients were included: 22 were confirmed COVID-19 and 11 were confirmed bacterial pneumonia. The median (interquartile range) age in COVID-19 and patients with bacterial pneumonia were 53 years (40– 64) vs 57 years (53– 71), respectively. Compared with patients with bacterial pneumonia, HJBLIs were significantly higher in COVID-19 patients [21/22 (80.8%) vs 5/11 (45.5%), p 0.001]. Conclusion: Howell-Jolly body-like inclusions could be a potential feature to help differentiate between COVID-19 and bacterial pneumonia. [ABSTRACT FROM AUTHOR]

Background: Dengue has become a major global health threat since being recognized three centuries ago. Important gaps remain in understanding the transmission dynamics of dengue virus (DENV) infection. This study reports the results of a prospective observational cluster study that investigated the incidence of symptomatic and asymptomatic infections and length of viremia among close community contacts of hospitalized DENV-infected patients. Methodology/principal findings: Between 2005 and 2009, dengue-confirmed cases (n = 97) admitted to Hasan Sadikin Hospital in Bandung, Indonesia, were enrolled as index cases. Subsequently, twenty close community contacts (n = 1928) living with and around the index cases were included and followed up for up to 14 days. Body temperature was measured daily; blood samples were collected every 3–4 days and when reported fever. DENV infection was confirmed using Reverse Transcriptase–Polymerase Chain Reaction (RT-PCR), IgM rapid test, and Enzyme-linked Immunosorbent Assay (ELISA). Among the 1928 community contacts, a total of 72 (3.7%) acute DENV infections were diagnosed, which equates to an incidence of 636 cases per 1,000 person-years (95% Confidence interval (CI) 588 to 687 cases per 1,000 person-years). Twenty-nine cases (40%) were symptomatic (22 dengue fever (DF) & 7 dengue hemorrhagic fever (DHF)), and 43 (60%) were asymptomatic. Primary and secondary DENV infections were detected in 18 (25%) and 54 (75%) subjects. Among the RT-PCR positives, viremia was observed as early as seven days before fever onset and converted to negative as late as seven days after the onset of fever. Conclusions: DENV infections are common among close community contacts of hospitalized dengue patients. The high number of asymptomatic infections and the observation that viremia precedes the onset of fever for up to seven days highlight the importance of unrecognized dengue transmission and the need for improved transmission control. Author summary: Data regarding a complete course of dengue viremia, especially in pre-febrile and asymptomatic cases, are limited. These data can be obtained from community cluster studies that enroll and follow up with the neighborhood and household members of dengue-confirmed index cases. Using this approach, we assessed the presence of dengue viremia before the development of fever and the incidence of symptomatic and asymptomatic dengue cases within the community contacts. We found that there are 1.5 asymptomatic dengue infections for each symptomatic case. Furthermore, dengue virus in blood was detected in eight out of sixteen post-enrollment dengue subjects before the onset of fever. The maximum period was up to seven days, longer than previously reported. Viremic subjects play a crucial role in dengue transmission by mosquitoes. Our data indicate that the significance of unnoticed virus transmission supports the need for comprehensive and sustainable vector control interventions. With the active surveillance embedded in the study design, we calculated the incidence of dengue infection to be 636 cases per 1,000 person-years of follow-up, 930 times higher than the national incidence rate around the same study period, showing the real burden of disease in a hyperendemic area and confirming the underestimation of Indonesian incidence data. [ABSTRACT FROM AUTHOR]

Background Medical and nursing students entering their clinical programmes are at increased risk for tuberculosis (TB) in TB-endemic settings. Relatively little is known about Mycobacterium tuberculosis infection among such students in high-endemic countries. Methods We examined M. tuberculosis infection among medical and nursing students starting clinical training in Bandung, Indonesia using interferon-γ release assay (IGRA) QuantiFERON-TB Gold Plus. IGRA-negative students had a repeat test after 1 y and logistic regression was used to identify factors associated with IGRA positivity or conversion. Results There were 379 students included in this study: 248 (65.4%) were medical students and 131 (34.6%) were nursing students. Of 379 students, 70 (18.5%) were IGRA positive at baseline. Of 293 IGRA-negative students with 1-y results, 26 (8.9%) underwent IGRA conversion. Being a medical student (adjusted relative risk [ARR] 5.15 [95% confidence interval {CI} 1.82 to 14.59], p=0.002) and participation in sputum collection or bronchoscopy were associated with IGRA conversion (ARR 2.74 [95% CI 1.29 to 5.79], p=0.008). Conclusions Medical and nursing students entering clinical training are at high risk of M. tuberculosis infection and need improved infection prevention and control strategies. [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]

Objective: Private practitioner's (PPs) collaboration for detection, diagnosis and treatment of tuberculosis (TB) is recommended by the World Health Organization and encouraged by the Indonesian National TB control programme. TB case management by PPs, however, are mostly not in line with current guidelines. Therefore, we developed an intervention package for PPs comprising of TB training, implementation of a mobile phone application for notification of TB cases and a 6-month regular follow-up with PPs. This study aimed to evaluate the feasibility of the intervention package to increase TB case detection and notification rates among PPs in five community health centre areas in Bandung City, Indonesia. Results: A total of 87 PPs were registered within the study area of whom 17 attended the training and 12 had the mobile phone application successfully installed. The remaining five PPs had phones that did not support the application. During the follow-up period, five PPs registered patients with TB symptoms and cases into the application. A total of 36 patients with TB symptoms were identified and 17 were confirmed TB positive. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV) is known to cause sporadic or explosive outbreaks. However, little is known about the endemic transmission of CHIKV. To ascertain the endemic occurrence of CHIKV transmission, we tested blood samples from patients with a non-dengue febrile illness who participated in a prospective cohort study of factory workers in Bandung, Indonesia. From August 2000 to June 2004, and September 2006 to April 2008, 1901 febrile episodes occurred and 231 (12.2%) dengue cases were identified. The remaining febrile cases were evaluated for possible CHIKV infection by measuring anti-CHIKV IgM and IgG antibodies in acute and convalescent samples. Acute samples of serologically positive cases were subsequently tested for the presence of CHIKV RNA by RT-PCR and/or virus isolation. A total of 135 (7.1%) CHIKV infections were identified, providing an incidence rate of 10.1/1,000 person years. CHIKV infections were identified all year round and tended to increase during the rainy season (January to March). Severe illness was not found and severe arthralgia was not a prominently reported symptom. Serial post-illness samples from nine cases were tested to obtain a kinetic picture of IgM and IgG anti-CHIKV antibodies. Anti-CHIKV IgM antibodies were persistently detected in high titers for approximately one year. Three patients demonstrated evidence of possible sequential CHIKV infections. The high incidence rate and continuous chikungunya cases in this adult cohort suggests that CHIKV is endemically transmitted in Bandung. Further characterization of the circulating strains and surveillance in larger areas are needed to better understand CHIKV epidemiology in Indonesia. Author Summary: Chikungunya is one of the neglected diseases. It has only attracted attention during outbreaks, in particular, the large epidemics in the Indian Ocean in 2005–2006. To our knowledge, there has never been any surveillance to determine the transmission of this virus among humans in non-outbreak settings. Such surveillance is particularly important because it will provide a better estimate of the disease burden and valuable information on how this virus is maintained outside outbreaks. Our study, conducted between 2000 and 2008 in Bandung, West Java, Indonesia, yielded several important findings: 1. Chikungunya is an important cause of fever among adults in Bandung, Indonesia. 2. The clinical symptoms are mostly mild and short lasting. 3. In addition to previously described epidemiological features involving episodic outbreaks, it is also continuously transmitted throughout the year. 4. A few patients may have experienced more than one chikungunya virus infection. 5. Only the Asian genotype was found and not the East Central South African genotype that was responsible for the 2005 outbreak in the Indian Ocean. 6. The persistence of IgM for a long period after illness may complicate the interpretation of laboratory results. [ABSTRACT FROM AUTHOR]

The antimicrobial peptide cathelicidin is critical in killing pathogens by innate immune cells, including Mycobacterium tuberculosis and Candida albicans. These pathogens often cause infections in opioid users, a risk that is greatly increased with concurrent human immunodeficiency virus (HIV) infection. Therefore, we examined the association between opioid use and cathelicidin in HIV-infected subjects from Bandung, Indonesia. The following three groups of HIV-infected individuals were included: (i) Active drug users: used heroin in the last 30 days; (ii) Methadone clients: received methadone maintenance therapy in the last 30 days; and (iii) Controls: never used opioids or did not use opioids in the year preceding inclusion. In addition to interviews, blood samples were taken to examine the RNA expression of cathelicidin. We found that the RNA expression of cathelicidin was significantly decreased ( p=0.007) in heroin users, compared with controls. Opioids are associated with immunosuppression, and cathelicidin could be an important factor in this association. However, more research is needed to examine the direct effects of decreased cathelicidin levels. [ABSTRACT FROM AUTHOR]