Purpose Hydrocephalus is a complex pediatric neurologic disorder characterized by abnormal cerebrospinal fluid (CSF) flow and ventricular dilation. It poses significant challenges in clinical management and often leads to severe morbidities despite treatment. This study explores the correlation between pre-shunt seizures in hydrocephalic children and inflammatory mediators and electrolyte imbalances in the CSF. Methods An analytical correlational study design was employed, utilizing a comprehensive array of clinical data, radiological databases, and cerebrospinal fluid (CSF) samples obtained from pediatric patients at seven neurosurgical centers. The study population consisted of children with hydrocephalus, both with and without a history of seizures. Sample selection followed strict inclusion and exclusion criteria. Laboratory examinations included a comprehensive CSF analysis for Na + , K + , Ca 2+ , Mg 2+ , IL-1β, IL-6, and TNF-α levels. Hydrocephalus imaging was based on established radiographic criteria, with particular focus on periventricular hypodensity. The analytical process explored the associations between inflammatory markers, electrolyte imbalances, periventricular hypodensity, and the occurrence of seizures. Result While most electrolytes showed no association with seizure activity, Mg2+ levels stood out as a notable exception. Specifically, higher Mg2+ levels were significantly correlated with seizure incidence, with a mean of 1.8 mEq/L (SD ± 0.4) and a p-value of 0.03. A significant difference in Ca2+ levels was also observed between hydrocephalus patients with marked periventricular hypodensity in the seizure and non-seizure groups. This finding was interesting because most studies have reported that hydrocephalic children with lower, not higher, electrolyte levels are more prone to seizures. Conclusion This study reveals significant associations between some electrolytes and seizure activity in pediatric hydrocephalus. Notably, Mg2+ levels were correlated with seizure incidence, suggesting a key role in seizure pathophysiology. Additionally, the observed differences in Ca2+ levels, particularly in patients with periventricular hypodensity, point to a potential connection between Ca2+ dysregulation, brain tissue alterations, and seizure susceptibility.

Immune dysregulation is a hallmark of human immunodeficiency virus (HIV) infection, characterized by persistent immune activation and systemic inflammation that drive T cell exhaustion and senescence, contributing to disease progression and non-AIDS comorbidities, most notably tuberculosis (TB). With rising HIV prevalence, the incidence of HIV-TB co-infection continues to rise, highlighting the need to understand their immunopathological interplay. This narrative review aims to examine the association between immune dysregulation in HIV-TB co-infection, with a focus on cytokine profiles and immunological biomarkers. Relevant literature was retrieved from multiple databases, with evidence demonstrating differential expression of cytokines—IL-17A, IFN-γ, TNF, IL-10, IL-6, IL-4, and IL-2—and T cell activation markers, such as CD38 and HLA-DR on CD4+ T cells in latent and active TB among HIV-infected individuals. These immune mediators are consistently co-expressed at higher levels in active TB compared to latent TB, suggesting heightened immune activation of both innate and adaptive immune responses in HIV-TB co-infection. However, these findings are largely based on observational data, and the precise mechanism by which cytokine and T cell biomarker dysregulation contributes to HIV-TB pathogenesis remains incompletely understood, underscoring the need for larger, mechanistic studies to address these gaps in the pathogenic pathway.

Purpose:Ventilator-associated pneumonia (VAP) is a common complication in intensive care units (ICUs) with high mortality rates. Early risk stratification is often limited by the lack of availability of complex prognostic scoring and microbiology turnaround time. This study aimed to assess the neutrophil-to-lymphocyte ratio (NLR) and systemic inflammatory response index (SIRI) on the day of VAP diagnosis as predictors of in-hospital mortality. Patients and Methods:We conducted a retrospective cohort study using secondary data from mechanically ventilated adult patients with VAP admitted to Hasan Sadikin General Hospital (a tertiary referral hospital in Bandung, Indonesia) from January 1, 2021 to December 31, 2022. VAP was confirmed by chart review using standard clinical and radiologic criteria occurring ≥48 hours after the start of mechanical ventilation, with endotracheal aspirate culture when available. The primary outcome was all-cause in-hospital mortality (death before hospital discharge). NLR and SIRI were calculated from the first complete blood count on the day of VAP diagnosis. Optimal cut-offs were determined using ROC analysis (Youden index). Survival was analyzed from VAP diagnosis until death or discharge. Results:Among 87 patients, 68 died in hospital and 19 survived to discharge. NLR had excellent discriminatory power for in-hospital mortality (AUC 0.981); a cut-off >11 had 100% sensitivity and 89.5% specificity. SIRI had good discriminatory power (AUC 0.860); a cut-off >16 had 64.7% sensitivity and 100% specificity. In univariable Cox models, NLR >11 was associated with increased mortality risk (HR 29.07; 95% CI 2.24-376.92), whereas SIRI >16 showed a non-significant trend (HR 1.55; 95% CI 0.93-2.57). Conclusion:NLR and SIRI obtained on the day of VAP diagnosis are simple, non-invasive laboratory markers that could aid in early risk stratification for in-hospital mortality in VAP. These markers should not replace but rather complement established clinical severity assessment and treatment decisions.

Purpose:Genetic diversity of Mycobacterium tuberculosis (Mtb) contributes to variations in host immune responses. The Modern Beijing (MB) sub-lineage (Lineage 2, L2) has been associated with reduced interferon-gamma (IFN-γ) responses compared with strains from other lineages. However, the influence of drug-resistance status on lineage-specific immune responses remains poorly understood. This study investigated IFN-γ responses induced by clinical Mtb isolates with different lineages and resistance profiles. Methods:Peripheral blood mononuclear cells (PBMCs) from 18 healthy adults were stimulated with lysates of clinical Mtb isolates representing the LAM and MB sub-lineages, including drug-sensitive (DS) and isoniazid mono-resistant (Hr-TB) variants. IFN-γ levels were measured using ELISA after 48-hour stimulation. Paired t-tests and two-way repeated-measures ANOVA were used to evaluate the effects of lineage, resistance status, and their interaction on IFN-γ responses. Results:MB isolates induced significantly lower IFN-γ levels than LAM isolates (15.30 ± 6.28 vs 19.16 ± 7.28 pg/mL; p < 0.001). Similarly, Hr-TB isolates induced lower IFN-γ responses than DS isolates (15.44 ± 6.39 pg/mL vs 19.02 ± 7.26 pg/mL; p < 0.001). Stratified analysis revealed that within the MB lineage, Hr-TB isolates significantly reduced IFN-γ production compared to DS isolates (13.14 ± 6.13 pg/mL vs 17.45 ± 5.81 pg/mL; p < 0.001). In contrast, no significant difference was observed between DS and Hr-TB isolates within the LAM lineage (p = 0.061). No significant interaction was observed between Mtb lineage and drug-resistance status on IFN-γ responses (p = 0.390). Conclusion:These findings demonstrate that IFN-γ responses to Mtb are influenced by both bacterial lineage and drug-resistance status. The MB sub-lineage, particularly in Hr-TB isolates, was associated with reduced IFN-γ production, indicating lineage-associated differences in immunomodulatory capacity. These findings provide insights into TB pathogenesis and may support the development of future vaccine or host-directed therapeutic strategies.

Background:People living with HIV (PLWH) presenting with advanced HIV have worse outcomes than those diagnosed earlier. The proportion of PLWH in Indonesia who are late presenters is unknown but likely high. Identifying factors associated with late presentation is key to earlier diagnosis and intervention. Methods:Adult PLWH were enrolled at 19 centers across Indonesia (2018-2020) in the INA-PROACTIVE observational cohort study. Late presentation was defined as having a CD4+ count <350 cells/μl within 3 months of diagnosis. Risk factors were assessed using multivariable logistic regression. Findings:Among 3201 eligible participants, 2790 (87·2%) were late presenters. High proportion of late presenters was observed from 2015 to 2019 (83·3%-89·8%). Characteristics associated with late presentation included age 30-39 (aOR = 1·47, 95% CI: 1·15-1·90) or age ≥40 (aOR = 1·71, 95% CI: 1·21-2·46) vs. age 18-29; male sex (aOR = 2·93, 95% CI: 2·07-4·24); diagnosis in ≤2015 (aOR = 1·45, 95% CI: 1·12-1·89); and diagnosis through Provider-Initiated Testing and Counseling (aOR = 2·38, 95% CI: 1·86-3·04) vs. Voluntary Counseling and Testing (VCT). Suspected MSM transmission was associated with lower odds of late presentation (aOR = 0·57, 95% CI: 0·39-0·82) compared to heterosexual transmission. Interpretation:Late presentation remains highly prevalent in Indonesia. Expanded efforts are needed to promote testing among those at risk. Targeted interventions for older adults, men, and non-MSM populations, alongside VCT and MSM-focused programs, may help reduce late HIV diagnosis and improve early management. Funding:This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, under contract No. 75N91019D00024 Task orders 75N91020F00004, 75N91020F000012.

Purpose:The syndemic of tuberculosis (TB) and type 2 diabetes mellitus (T2DM) presents a growing global health challenge, particularly in high-burden countries. T2DM is known to impair immune responses, increasing susceptibility to TB. However, the cytokine dynamics underlying this interaction remain unclear. This study aimed to explore the differences in ex vivo cytokine responses between individuals with and without T2DM following TB antigen stimulation. Patients and Methods:In this cross-sectional study, we analyzed plasma samples from 110 individuals with T2DM and 38 without, collected as part of the TANDEM and INFECT cohort studies in Indonesia. Cytokine levels (IL-1β, IL-6, TNF-α, and IFN-γ) were measured using ELISA before and after TB antigen stimulation using the QuantiFERON-TB Gold assay. Demographic, clinical, and metabolic parameters were recorded. Statistical analyses included Mann-Whitney U-tests and Spearman correlation. Results:Patients with DM showed a higher baseline levels of pro-inflammatory cytokines than non-DM individuals, particularly in IL-1β, IL-6 and TNF-α, suggesting a primed immune response even before TB antigen exposure. After TB antigen stimulation, no significant between-group differences were observed in cytokine levels. However, IL-1β showed a more pronounced median increase in T2DM (124 vs -54 pg/mL, p = 0.43), while IL-6, TNF-α, and IFN-γ changes were blunted in the T2DM group. Correlation analyses revealed that in T2DM individuals, IL-1β positively correlated with IL-6 and TNF-α both pre- and post-stimulation. IL-6 and IFN-γ showed significant associations with HbA1c and BMI in the non-DM group. Conclusion:T2DM group exhibited altered immune patterns marked by heightened IL-1β response and disrupted regulation of IL-6, TNF-α, and IFN-γ, although no statistically significant cytokine differences were observed. These findings suggest an immune dysregulation in T2DM that may contribute to TB susceptibility, warranting further investigation using CD4/CD8-responsive assays in larger, more diverse populations.

Introduction: Multiple inflammatory markers, including high sensitivity C-reactive protein (hsCRP), procalcitonin, interleukin-6 (IL-6), D-dimer, lactate dehydrogenase (LDH), and ferritin, have demonstrated significant sensitivity as predictors of COVID-19 severity. However, there is a paucity of research investigating the association of IL-6, CRP, and interferon-gamma (IFN-gamma) with day of illness in confirmed mild and moderate pulmonary COVID-19 cases in Indonesia. Methods: This retrospective analytic study utilised secondary data extracted from the medical records. The study was conducted over a nine-month period, from December 2020 to October 2021, and included a total of 80 subjects. These subjects were categorised into 60 mild and 20 moderate COVID-19 cases. Results: Analysis revealed a statistically significant difference in median IL-6 levels, with moderate cases exhibiting higher levels than mild cases (4.50 pg/mL vs. 2.87 pg/mL, difference = 1.63 pg/mL; p=0.008). Similarly, median hsCRP levels were significantly elevated in moderate cases compared to mild cases (3.85 mg/L vs. 0.90 mg/L, difference = 2.95 mg/L; p=0.001). Conversely, IFN-gamma levels did not demonstrate a significant difference between moderate and mild cases (0.23 pg/mL vs. 0.28 pg/mL; p=0.907). Regarding temporal trends, IL-6 levels tended to increase until the fourth day of illness before declining on the fifth day. hsCRP levels were elevated on the first and fourth days but decreased by the fifth day, while IFN-gamma concentrations peaked on the first and third days. Conclusion: This study demonstrates a significant elevation in IL-6 and hsCRP levels in patients with confirmed moderate COVID-19, compared to those with mild disease. However, no significant difference was observed in IFN-gamma levels between these two groups. Peak levels of IL-6 and hsCRP were recorded on day 1 and day 4 of illness, respectively.

The elderly population is at high risk of severe complications from influenza due to decreased effectiveness of the immune response (Immunosenescence). Trivalent influenza vaccines are designed to boost immunity and provide protection against some influenza virus strains. The research aims to evaluate the effectiveness of the trivalent influenza vaccine in enhancing immune response in elderly populations by examining specific immunological parameters. A total of 44 elderly participants were vaccinated with one of three trivalent influenza vaccines: A/Singapore – EFTHA 1835, A/Singapore – EFTHAS 1828, and B/Maryland – EFTTHAC 1822. Antibody titers were measured using the Hemagglutination Inhibition (HAI) test before and after vaccination. Levels of immunological markers IL-15, MIP-1α, IFN-γ, and CD16 were assessed using an enzyme-linked immunosorbent assay (ELISA). Before immunization, HAI titers were low in all groups. After vaccination, all groups showed a significant increase in HAI titers (p = 0.000), with the largest increase in group A/Singapore – EFTHA 1835. IL-15 and MIP-1α levels increased, while IFN-γ (p = 0.003) and CD16 levels decreased significantly. The trivalent influenza vaccine effectively enhances the immune response in the elderly population, evidenced by increased HAI titers and significant changes in immunological markers.

Although many high-income countries have regular COVID-19 vaccine booster schedules, there are limited data on the protective effects of some heterologous booster combinations. This observational follow-up study of a double blind randomised controlled parallel group trial evaluates long-term immunogenicity, safety and breakthrough infections to 24 months after booster doses (fractional or standard Pfizer BNT162b2, fractional or standard AstraZeneca ChAdOx1, and standard dose CoronaVac) following CoronaVac and AstraZeneca primary series in healthy adults in Indonesia. Of 1,289 trial participants, 962 (75%) complete follow-up to 24 months. Among CoronaVac-primed participants, responses are lower for fractional than standard dose Pfizer at 28 days (binding IgG geometric mean ratio: 0.75, 95% CI: 0.63-0.90), but differences diminish by 12 and 24 months. AstraZeneca-primed participants have lower initial responses than CoronaVac-primed participants following Pfizer and AstraZeneca boosters. Breakthrough infections occurred in >40% of participants between six and 12 months, and in >35% between 12 and 24 months. Fractional and standard doses of AstraZeneca and Pfizer among CoronaVac-primed or AstraZeneca-primed participants, boost immune responses to 24 months. However, fractional doses elicit lower initial responses than standard doses. These findings provide important information for booster strategies, especially in populations primed with inactivated vaccines. Funding: Coalition for Epidemic Preparedness Innovations (CEPI). Trial registration: ina-registry.org , INA-GO0HLGB.

Background and Objectives: The prevalence of stunted children under 5 years in Indonesia is relatively high. Stunting is a significant risk factor for wheezing disorders. The asthma predictive index (API) identifies children with a recurrent wheezing disorder at risk of developing asthma during the first 3 years. However, the risk of developing asthma and its associated factors among stunted children has not been studied. This study aims to determine the asthma risk prevalence in stunted children via the API score and associated factors. Materials and Methods: This cross-sectional study was conducted at the Bandung District Health Center from October 2021 to January 2022. This study included stunted children aged 24–59 months living in Bandung District whose parents could answer the API and asthma risk factor questionnaires. Results: A total of 422 participants with an average age of 43.1 ± 9.7 months were included. Among the stunted children, 4.7% (20/422) met the positive API criteria, and 50.0% were malnourished (stunted–underweight). The participants with positive API results had a parental medical diagnosis of asthma (45%), eczema (10.0%), allergic rhinitis (20.0%), and wheezing apart from colds (40.0%) (p < 0.05). Significant risk factors for developing asthma in the participants with a positive API were dog ownership in the past 12 months and parents and siblings with allergic diseases. Conclusions: The asthma risk prevalence in stunted children was 4.7%. The associated risk factors included a history of allergic diseases in parents and siblings, as well as dog ownership; however, further investigation is needed.

BACKGROUND:Erythrocyte indices are measuring tools for differentiating beta thalassemia (β-thalassemia) minor from other microcytic hypochromic anemias using routine hematological parameters. Although indices such as the Mentzer Index, Shine and Lal (S&L), Green and King, Ehsani, and Srivastava are widely applied, diagnostic accuracy remains limited when compared to hemoglobin electrophoresis, which serves as the gold standard. OBJECTIVE:To compare the performance of two newly developed erythrocyte formulas for identifying β-thalassemia minor in comparison with five commonly used indices. METHODS:A cross-sectional study was conducted on 54 males and 214 female subjects with microcytic hypochromic anemia. Two new formulas were developed based on Mean Corpuscular Hemoglobin Concentration (MCHC), a parameter available in simple hematologic analyzers. The first formula was derived using the binary logistic regression method (21.33 + 0.9MCH-1.3MCHC), while the second was constructed as a ratio of Mean Corpuscular Volume (MCV) and MCHC (MCV/MCHC2 × 100). Diagnostic performance was compared against other widely used erythrocyte indices. RESULTS:Shine and Lal Index had the highest sensitivity compared to all erythrocyte indices (98.65%). However, the newly developed formulas had the highest specificity (92.50% and 90.01%), positive predictive value (PPV) (93.48% and 91.55%), negative predictive value (NPV) (85.38% and 85.71%), accuracy (89.55% and 88.81%), Youden Index (79.66% and 77.85%), and Area Under the Curve (AUC) (0.932 and 0.934) compared to all erythrocyte indices. CONCLUSION:The two new MCHC-based formulas had the best diagnostic performance compared with other erythrocyte indices, while Shine and Lal Index had the highest sensitivity.

Approximately 10-35% of people living with HIV (PLHIV) on antiretroviral therapy (ART) fail to restore CD4+ T cell counts, a state known as immunological non-responder (INR) characterized by persistent immune activation and elevated cytokine levels. Objective: This study aimed to identify cytokines that can serve as biomarkers for immune activation and inflammation in INR patients. Methods: We conducted a cross-sectional study comparing two groups: INRs (PLHIV on ART with viral suppression) and immunological responders (IRs). We analyzed 40 samples of virologically suppressed PLHIV, measuring CD4+ T cell counts, viral load via RT-PCR, and cytokine levels through cytometric bead array (CBA). Results: The INR group exhibited significantly higher median serum levels of IL-6 (1.74 pg/mL vs. 0.94 pg/mL, p = 0.016) and IL-10 (1.65 pg/mL vs. 0.92 pg/mL, p = 0.03) compared to the IR group. Conclusions: Elevated IL-6 and IL-10 levels may serve as potential markers to distinguish INR from IR patients with areas under the curve (AUC) of 0.731 and 0.707, respectively.

Tuberculosis (TB) remains a global public health problem. The determination of tuberculosis infection (TBI) using interferon-gamma release assay has now been used widely. We aim to evaluate the positivity rates of Standard E TB-Feron enzyme-linked immunosorbent assay (TB-Feron ELISA) and Standard F TB-Feron fluorescent immunoassay (TB-Feron FIA) and their agreement with QuantiFERON-TB Gold Plus (QFT-Plus) among TB high-risk populations in Bandung City, Indonesia. We conducted a cross-sectional study, including people with a high risk of acquiring TB. We screened subjects for TB symptoms and offered chest X-ray (CXR). Anyone with cough or CXR suggestive of TB was asked to give sputum samples for GeneXpert MTB/RIF Ultra test. The positivity rates and corresponding 95% confidence intervals (CI) were calculated among patients with bacteriologically confirmed TB and among patients with no evidence of TB, no history of TB, and no known contact with TB patient (low risk of TBI). The agreement with QFT-Plus was calculated using Cohen's κ score. We enrolled 527 subjects, and the proportion of positive results among bacteriologically confirmed TB patients were 8 (53.3%; 95% CI 26.6-78.7), 9 (60.0%, 95% CI 32.3-83.7), and 10 (66.7%, 95% CI 38.4-88.8) by TB-Feron FIA, TB-Feron ELISA and QFT-Plus. The agreement between TB-Feron FIA and QFT-Plus among all subjects was similar to that of TB-Feron ELISA and QFT-Plus (84.1%, κ = 0.66, 95% CI 0.59-0.72). TB-Feron FIA and TB-Feron ELISA showed an acceptable clinical performance compared with QFT-Plus. These tests are useful alternatives for detecting TB infection.IMPORTANCEThis study evaluates the performance of two alternative interferon-gamma release assays, Standard E TB-Feron enzyme-linked immunosorbent assay and Standard F TB-Feron fluorescent immunoassay, for diagnosing tuberculosis infection (TBI) among high-risk populations in Bandung, Indonesia. Both assays demonstrated comparable clinical performance to the widely used QuantiFERON-TB Gold Plus (QFT-Plus). Given the global burden of tuberculosis, particularly in resource-limited settings, these findings suggest that the TB-Feron assays could serve as reliable alternatives to QFT-Plus for TBI detection. This research highlights the potential for these assays to improve tuberculosis diagnosis, offering a more accessible and efficient screening tool, especially for high-risk populations, and supporting broader tuberculosis surveillance.

Background: Numerous studies have proved the efficacy of vaccination in reducing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission and the coronavirus disease (COVID-19) burden. However, even though the COVID-19 vaccination coverage is high for primary doses, a booster dose is needed to sustain protection. Continuing our previous research, this study evaluates the immunogenicity and safety of full and half doses of two COVID-19 booster vaccines, ChAdOx1-S (AstraZeneca) and BNT162b2 (Pfizer-BioNTech), in individuals primed with ChAdOx1-S. Methods: This study was an observer-blind randomized controlled trial to evaluate the immunogenicity and safety of half and full doses of two COVID-19 booster vaccine types, BNT162b2 and ChAdOx1-S, among fully vaccinated, ChAdOx1-S-primed individuals in Jakarta, Indonesia. A total of 329 participants were randomized to receive either full or half doses of the booster vaccines, namely the ChAdOx1-S and BNT162b2 COVID-19 vaccines. Immunogenicity was assessed through SARS-CoV-2 antibody titers and neutralizing antibodies (NAbs) at 28 days post-booster, while safety was monitored via adverse event reporting. Results: The results showed that both vaccines demonstrated increased geometric mean titers (GMTs) post-booster. In the ChAdOx1-S booster group, at the baseline visit (day 0) and third visit (day 28), no statistically significant differences in GMT between the half- and full-dose groups were observed (p = 0.970 and 0.539, respectively). In the BNT162b2 group, no statistically significant difference was noted at the baseline visit, while the full dose was higher than the half dose at 28 days (Day 28, p = 0.011). Surrogate virus neutralization tests (sVNTs) and NAbs assays also revealed no significant differences between the half and full dose groups for both the Wuhan strain and the Delta variant. The BNT162b2 group compared to the ChAdOx1-S group revealed a statistically significant increase in IgG levels compared to ChAdOx1-S, with p-values of <0.001 and <0.001 for the half dose and full dose, respectively. This was also reflected in the NAbs test results, where BNT162b2 showed significantly higher levels against both the Wuhan strain and Delta variant. Adverse events were predominantly mild: 79.6% (n = 86/108) in the ChAdOx1-S full-dose group, 75.4% (n = 43/57) in the ChAdOx1-S half-dose group, 84.2% (n = 101/120) in the BNT162b2 full-dose group, and 92.6% (n = 88/95) in the BNT162b2 half-dose group, with pain at the injection site being the most common local reaction and myalgia and headache the most frequent systemic reactions. One serious adverse event was reported, assessed as unrelated to the vaccine. Conclusions: This study confirms that half doses of ChAdOx1-S and BNT162b2 are as immunogenic and safe as full doses, and a heterologous booster is more immunogenic than a homologous booster.

AbstractSome individuals, even when heavily exposed to an infectious tuberculosis patient, do not develop a specific T-cell response as measured by interferon-gamma release assay (IGRA). This could be explained by an IFN-γ-independent adaptive immune response, or an effective innate host response clearing Mycobacterium tuberculosis (Mtb) without adaptive immunity. In heavily exposed Indonesian tuberculosis household contacts (n = 1347), a persistently IGRA negative status was associated with presence of a BCG scar, and - especially among those with a BCG scar - with altered innate immune cells dynamics, higher heterologous (Escherichia coli-induced) proinflammatory cytokine production, and higher inflammatory proteins in the IGRA mitogen tube. Neither circulating concentrations of Mtb-specific antibodies nor functional antibody activity associated with IGRA status at baseline or follow-up. In a cohort of adults in a low tuberculosis incidence setting, BCG vaccination induced heterologous innate cytokine production, but only marginally affected Mtb-specific antibody profiles. Our findings suggest that a more efficient host innate immune response, rather than a humoral response, mediates early clearance of Mtb. The protective effect of BCG vaccination against Mtb infection may be linked to innate immune priming, also termed ‘trained immunity’.

Indonesia has one of the highest HIV infection rates in Southeast Asia. The use of dolutegravir, an integrase strand transfer inhibitor (INSTI), as a first-line treatment underscores the need for detailed data on INSTI drug resistance mutations (DRMs). Currently, there is a lack of comprehensive data on DRMs INSTI and other HIV drug resistance in Indonesian patients, both pre- and post-treatment. The aim of this study was to identify the subtypes and drug resistance mutations of the protease, reverse transcriptase, and integrase genes in both treatment-naive and ARV-treated patients in Bandung, West Java, Indonesia. A cross-sectional study was conducted involving HIV- positive patients at Hasan Sadikin Hospital, Bandung, Indonesia, from September 2022 to January 2023. The patients were categorized into two groups: ARV-treated and pre- treatment patients. Peripheral blood mononuclear cells (PBMCs) were processed for DNA extraction, followed by amplification and sequencing of the pol gene to detect mutations and subtypes. The study found that the predominant subtype was CRF01_AE, accounting for 85.4% and 69% of pre-treatment and treated patients, respectively, followed by recombinant forms such as A1/CRF01_AE, CRF01_AE/CRF02_AG, subtype B, and other subtypes. Among ARV-treated/INSTI-naive patients, major INSTI DRMs R263 K and Y143H were identified, while pre-treatment patients exhibited accessory integrase DRMs. The most common DRMs detected were non-nucleoside reverse transcriptase inhibitor (NNRTI) DRMs, with prevalences of 14.6% and 7% in pre-treatment and ARV-treated patients, respectively. In conclusion, CRF01_AE emerged as the predominant subtype in both pre-treatment and ARV-treated patients in Bandung, underscoring the necessity for ongoing surveillance of integrase DRMs, particularly given the presence of major INSTI DRMs in patients undergoing INSTI treatment.

COVID-19 infection in high-risk populations is fatal and has a poor prognosis, necessitating a test to determine the protectiveness of immune response. Antibody testing is necessary to determine the body’s immune response to COVID-19 infection and also vaccination strategies. Among the various methods available, the chemiluminescent immunoassay (CLIA) test is more widely used and accessible to determine antibody levels. This study aimed to determine the protection level of S-RBD SARS-CoV-2 IgG using CLIA compared to the Surrogate Virus Neutralization Test (SVNT). The population of this study comprised all healthcare professionals who experienced S-RBD SARS-CoV-2 IgG antibody level examinations. S-RBD SARS-CoV-2 IgG antibody levels were examined using CLIA and SVNT. The cut-off was determined using a receiver operating characteristic (ROC) curve, and area under the curve (AUC) measurements were evaluated. The result showed a strong positive correlation between S-RBD SARS-CoV-2 IgG CLIA and SVNT, with a value of r = 0.933 and p < 0.001. The value ≥ 37.29 BAU/mL was determined as the cut-off based on SVNT 30% inhibition level with sensitivity, specificity, and positive and negative predictive values of 96.5%, 90.9%, 96.5%, and 90.9%, respectively. A titer of antibodies greater than or equal to 37.29 BAU/mL with CLIA showed the presence of protective antibodies compared to SVNT.

Infection of Human Immunodeficiency Virus (HIV) lowers the body's immune system, especially CD4+ cells, making it more susceptible to opportunistic infections. Approximately 10-40% of People Living with HIV/AIDS (PLHIV) fail to achieve normal levels of CD4+ T cells despite continued virological suppression, a condition called Immunological Non-Responders (INR). Previous studies have shown that INR is considered a predictor of disease progression in people with HIV receiving antiretroviral (ARV)s through various mechanisms of suppression of the immune system that increases morbidity and mortality. Papua is an HIV epidemic area with a prevalence of 2.3%. This research is a cohort study conducted at Abepura Hospital from June 2019 to February 2023, which aims to identify the factors that influence the occurrence of INR in PLHIV receiving ARV therapy. There were 123 research subjects consisting of 55 people (44.7%) in the INR group and 68 people (55.3%) in the non-INR group. The results showed that the incidence of INR was higher in males than females (p=0.019), INR was significantly associated with increasing age (p=0.013), and CD4 count was low at the start of ARVs (p=0.002). There was a significant difference in CD4 counts between INR and non-INR (p<0.001). Oral candidiasis as a common opportunistic infection is more common in people with INR than in non-INR. (p=0.037). This study suggested that it is necessary to carry out a CD4 examination at the start of therapy and monitoring every 6 months to detect possible INR to prevent an increased risk of AIDS and non-AIDS, which increases mortality.

Individuals with human immunodeficiency virus (HIV) infection are susceptible to immune system dysregulation, particularly during co-infection with Mycobacterium tuberculosis (MTB). Although there is an association between cytokine profiles and HIV-MTB co-infection, little is known about the cytokine-related host immune response mechanism to HIV-MTB co-infection. Therefore, the present study aimed to analyze expression of cytokines IL-17A, IFN-gamma, TNF, IL-2, IL-10, IL-6 and IL-4 in individuals with HIV-MTB co-infection. A total of 30 patients with HIV and 40 with HIV-MTB co-infection were recruited into the present study, including those with active (A) (n=19) and latent (L)TB (n=21). HIV infection status was established based on national HIV guideline (Pedoman Nasional Pelayanan Kedokteran Tatalaksana HIV). ATB was confirmed using a positive acid-fast bacillus staining and culture of sputum; LTB status was established using IFN-gamma release assay. Furthermore, the levels of cytokines IL-17A, IFN-gamma, TNF, IL-10, IL-6, IL-4 and IL-2 were measured using flow cytometric bead array and CD4 cell count was performed by PIMA (TM) CD4 assay. IFN-gamma, TNF, IL-10, IL-6 and IL-2 were able to significantly differentiate patients with HIV-ATB from those with HIV-LTB. Furthermore, in the patient subgroup with CD4 count <350 cells/l, IFN-gamma, IL-10 and IL-6 were able to differentiate between patients with HIV-ATB and HIV alone, as well as between patients with HIV-ATB and HIV-LTB. Based on these findings, the cytokine profiles are likely to be distinct between individuals with HIV infection with A- and LTB. Furthermore, the expression of CD4-positive T cells may influence the immune response in the body under HIV-MTB co-infection.

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.