Stunting as a Risk Factor for Asthma: The Role of Vitamin D, Leptin, IL-4, and CD23.

Stunting, which results from chronic malnutrition, is common in children from low- and middle-income countries. Several studies have reported an association between obesity and asthma. However, only a handful of studies have identified stunting as a significant risk factor for wheezing, a symptom of asthma, although the underlying mechanism remains unclear. This article aimed to review possible mechanisms underlying asthma in stunted children. Overall, changes in diet or nutritional status and deficiencies in certain nutrients, such as vitamin D, can increase the risk of developing asthma. Vitamin D deficiency can cause linear growth disorders such as stunting in children, with lower levels of 25(OH)D found in underweight and stunted children. Stunted children show a decreased lean body mass, which affects lung growth and function. Low leptin levels during undernutrition cause a Th1-Th2 imbalance toward Th2, resulting in increased interleukin (IL)-4 cytokine production and total immunoglobulin E (IgE). Studies in stunted underweight children have also found an increase in the proportion of the total number of B cells with low-affinity IgE receptors (CD23+). CD23+ plays an important role in allergen presentation that is facilitated by IgE to T cells and strongly activates allergen-specific T cells and the secretion of Th2-driving cytokines. Stunted children present with low vitamin D and leptin levels, impaired lung growth, decreased lung function, and increased IL-4 and CD23+ levels. All of these factors may be considered consequential in asthma in stunted children.

Early Clearance of Mycobacterium tuberculosis: The INFECT Case Contact Cohort Study in Indonesia.

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.

Early Clearance of Mycobacterium tuberculosis Is Associated With Increased Innate Immune Responses.

BACKGROUND: A proportion of tuberculosis (TB) case contacts do not become infected, even when heavily exposed. We studied the innate immune responses of TB case contacts to understand their role in protection against infection with Mycobacterium tuberculosis, termed "early clearance." METHODS: Indonesian household contacts of TB cases were tested for interferon-γ release assay (IGRA) conversion between baseline and 14 weeks post recruitment. Blood cell populations and ex vivo innate whole blood cytokine responses were measured at baseline and, in a subgroup, flow cytometry was performed at weeks 2 and 14. Immunological characteristics were measured for early clearers, defined as a persistently negative IGRA at 3 months, and converters, whose IGRA converted from negative to positive. RESULTS: Among 1347 case contacts, 317 were early clearers and 116 were converters. Flow cytometry showed a resolving innate cellular response from 2 to 14 weeks in persistently IGRA-negative contacts but not converters. There were no differences in cytokine responses to mycobacterial stimuli, but compared to converters, persistently IGRA-negative contacts produced more proinflammatory cytokines following heterologous stimulation with Escherichia coli and Streptococcus pneumoniae. CONCLUSIONS: Early clearance of M. tuberculosis is associated with enhanced heterologous innate immune responses similar to those activated during induction of trained immunity.

Association of first trimester maternal vitamin D, ferritin and hemoglobin level with third trimester fetal biometry: result from cohort study on vitamin D status and its impact during pregnancy and childhood in Indonesia.

INTRODUCTION: The role of vitamin D in placental functions and fetal growth had been addressed in many reports with conflicting results. However, such report is limited for Indonesian population. The aim of this study was to explore the association between maternal vitamin D level in the first trimester and fetal biometry in the later stage of pregnancy with adjusted OR for other determinants like hemoglobin and ferritin level. METHODS: From July 2016 a prospective cohort study of pregnant women had begun in four cities in West Java, Indonesia. Data on maternal vitamin D, ferritin, hemoglobin level, maternal demography and fetal biometry were analyzed with linear regression. RESULTS: Among 203 recruited women, 195 (96.06%) had hypovitaminosis D. One hundred fifty two (75%) were in deficient state and 43 women (21%) were in insufficient state. Women with insufficient vitamin D had the highest proportion of anemia, while women with normal vitamin D level had the highest proportion of low ferritin level. Maternal serum vitamin D showed significant associations with biparietal diameter (ß = 0.141, p = 0.042) and abdominal circumference (ß = 0.819, p = 0.001) after adjustment with maternal age, pre-pregnancy body mass index, parity, serum ferritin level, and hemoglobin level. CONCLUSION: Our study suggested that sufficient maternal vitamin D level was an important factor to improve fetal growth and development.

Optimizing ultraviolet B radiation exposure to prevent vitamin D deficiency among pregnant women in the tropical zone: report from cohort study on vitamin D status and its impact during pregnancy in Indonesia.

BACKGROUND: Vitamin D deficiency during pregnancy carries potential threat to fetal well being. Natural conversion of vitamin D in the skin can be facilitated by direct ultra violet B (UVB) radiation, but the effect is reduced by wearing umbrellas, clothes, or sunblock cream. Muslim women wear hijab that allows only face and hands to be seen. With increasing proportion of muslim women wearing hijab and the lack of vitamin D fortification and fish consumption in Indonesia, it poses a problem for vitamin D deficiency among pregnant women. This study aimed at finding the best timing of UVB exposure and the duration of exposure which can be suggested to prevent vitamin D deficiency among pregnant women, for those wearing hijab or not. METHODS: This study recruited 304 pregnant women in the first trimester, 75-76 women from 4 cities of the most populated province, West Java, Indonesia which represented 70-80% percent of pregnancy per year. A 3-day notes on duration, time and type of outdoor activity and the clothing wore by the women were collected. UVB intensity radiation were obtained. Calculation on body surface area exposed to direct UVB radiation and UVB radiation intensity were done. Measurement of vitamin D level in sera were done on the same week. RESULTS: The median of maternal sera vitamin D level was 13.6 ng/mL and the mean exposed area was around 0.48 m2 or 18.59% of total body surface area. Radiation intensity reached its peak around 10.00 and 13.00, but the mean duration of exposure to UVB during this window was lower than expected. Significant correlation was found between maternal sera vitamin D level and exposed body surface area (r = 0.36, p < 0.002) or percentage of exposed body surface (r = 0.39, p < 0.001) and radiation intensity (r = 0.15, p = 0.029). Further analysis showed that duration of exposure to UVB should be longer for pregnant women wearing hijab as compared to women without hijab. CONCLUSION: This study suggested that the best timing to get UVB exposure was between 10.00-13.00, with longer duration for women wearing hijab (64.5 vs 37.5 min) of continuous exposure per day.

EFFECT OF HIV PREVENTION AND TREATMENT PROGRAM ON HIV AND HCV TRANSMISSION AND HIV MORTALITY AT AN INDONESIAN NARCOTIC PRISON.

Validated data regarding HIV-transmission in prisons in developing countries is scarce. We examined sexual and injecting drug use behavior and HIV and HCV transmission in an Indonesian narcotic prison during the implementation of an HIV prevention and treatment program during 2004-2007 when the Banceuy Narcotic Prison in Indonesia conducted an HIV transmission prevention program to provide 1) HIV education, 2) voluntary HIV testing and counseling, 3) condom supply, 4) prevention of rape and sexual violence, 5) antiretroviral treatment for HIV-positive prisoners and 6) methadone maintenance treatment. During a first survey that was conducted between 2007 and 2009, new prisoners entered Banceuy Narcotics Prison were voluntary tested for HIV and HCV-infection after written informed consent was obtained. Information regarding sexual and injecting risk behavior and physical status were also recorded at admission to the prison. Participants who tested negative for both HIV and HCV during the first survey were included in a second survey conducted during 2008-2011. During both surveys, data on mortality among HIV-seropositive patients were also recorded. All HIV-seropositive participants receive treatment for HIV. HIV/ AIDS-related deaths decreased: 43% in 2006, 18% in 2007, 9% in 2008 and 0% in 2009. No HIV and HCV seroconversion inside Banceuy Narcotic Prison were found after a median of 23 months imprisonment (maximum follow-up: 38 months). Total of 484.8 person-years observation was done. Participants reported HIV transmission risk-behavior in Banceuy Prison during the second survey was low. After implementation of HIV prevention and treatment program, no new HIV or HCV cases were detected and HIV-related mortality decreased.

The number of CCR5 expressing CD4+ T lymphocytes is lower in HIV-infected long-term non-progressors with viral control compared to normal progressors: a cross-sectional study.

BACKGROUND: The HIV co-receptors CXCR4 and CCR5 play an important role in HIV infection and replication. Therefore we hypothesize that long-term non-progressors (LTNP) with viral control have lower expression of CCR5 and CXCR4 on CD4(+) cells, specifically on memory T-lymphocytes since they are the primary target cells of HIV. METHODS: In this cross-sectional study, we included five HIV-infected LTNP with viral control (CD4 > 750 cell/µl & HIV < 50 copies for ≥2 years), thirteen HIV-infected and seven HIV-uninfected individuals at Radboud UMC Nijmegen, the Netherlands. We determined the CCR5 and CXCR4 expression among CD4(+) and CD8(+) lymphocyte subsets; memory (CD45RO(+)), naïve (CD45RA(+)) cells and regulatory T-cells (CD4(+)CD25(high)FoxP3(+)). In addition, CCR5∆32 polymorphism is related with disease progression and was therefore determined using polymerase chain reaction. RESULTS: The percentage of CCR5-expressing CD4(+) cells of LTNP was comparable with healthy controls; whereas HIV-infected individuals showed more CCR5-expressing cells. This was observed in memory and naïve CD4(+) cells, but not in regulatory T-cells. The mean fluorescence intensity of CCR5-expressing CD4(+) cells was similar in all groups. All groups had comparable percentages of CXCR4-expressing cells. The mean fluorescence intensity of CXCR4-expressing cells was significantly higher in HIV-infected normally progressors in both memory and naïve CD4(+) cells, but not in CD8(+) cells. The CCR5∆32 polymorphism was not related to group. CONCLUSIONS: We show that HIV affects -directly or indirectly- the expression of CCR5 in CD4(+) T-lymphocytes; yet this effect is not seen in LTNP with viral control. Avoiding upregulation of CCR5 could be an important method via which LTNP counteracts the effects of HIV and suppresses viral replication. Exploring how LTNP suppress the upregulation of CCR5 could be an important step for discovering new therapeutics.

Lesson Learned from Mass Antibody Rapid Diagnostic Used in the Early COVID-19 Pandemic in Indonesia Contributors.

Introduction: Laboratory examination is extremely important in handling the COVID-19 pandemic. In the first era of the pandemic, the molecular and antigen tests were limited. Hence, at that time, it was necessary to carry out antibody Rapid Diagnostic Tests (RDT). However, many antibody RDTs were yet to obtain Food and Drug Authorization (FDA)'s approval. Purpose: Therefore, The Indonesian Association of Clinical Pathology and Medical Laboratory (PDS PatKLIn) decided to conduct a validity test of RDT antibodies to find out the quality of SARS-CoV-2 diagnosis performance based on these RDTs used. Patient and Methods: This is a descriptive observational design with diagnostic analysis. The retrospective secondary data were collected from 34 provinces in Indonesia from May to June 2020. Data analysis was carried out on the sensitivity and specificity values of each antibody RDT brand to the RT-PCR result and analyzed descriptive data. Results: The amount of secondary data of antibody RDT and RT-PCR results collected was 139,908, consisting of 59 RDT brands of which 44% were authorized by The Indonesian COVID-19 Response Acceleration Task Force (Gugus Tugas Percepatan Penanganan COVID-19 Indonesia). There were huge variations of SARS-CoV-2 antibody RDT performance between total antibody types (sensitivity 59.18%, specificity 62%), IgM RDT (sensitivity 16-100%, specificity 7-97%), and RDT IgG (sensitivity 33-96%, specificity 19-100%). Conclusion: The variations in the RDT antibodies'performance can cause errors in diagnosis leading to significant material and immaterial losses. Therefore, cooperation from various parties is needed for the pre- and post-marketing surveillance process to assess the performance and the characteristics of each RDT kit and other diagnostic methods to assist the rapid pandemic response process.

The Protection Level of S-RBD SARS-CoV-2 Immunoglobulin G Antibodies Using the Chemiluminescent Immunoassay Compared to the Surrogate Virus Neutralization Test Method.

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.

Accuracy of Anti-SARS-CoV-2 Antibody in Comparison with Surrogate Viral Neutralization Test in Persons Living with HIV, Systemic Lupus Erythematosus, and Chronic Kidney Disease.

The presence of the anti-SARS-CoV-2-RBD antibody (anti-RBD) prevents severe COVID-19. We aimed to determine the accuracy of a point-of-care anti-RBD testing implemented in persons living with HIV (PLWH), systemic lupus erythematosus (SLE), and chronic kidney disease (CKD). We enrolled 182 non-comorbid subjects and 335 comorbid subjects (PLWH, SLE, CKD) to test the anti-RBD assay compared to the surrogate viral neutralization test (sVNT) as the reference test. We performed linear correlation analysis between anti-RBD and sVNT, along with an ROC analysis to ascertain the anti-RBD cutoff at 30%, 60%, and 90% inhibition of sVNT, to calculate accuracy. The correlations between anti-RBD and sVNT among all groups were excellent, with R = 0.7903, R = 0.7843, and R = 0.8153 among the non-comorbid, SLE, and CKD groups, respectively, and with significantly higher correlation among the PLWH group (R = 0.8877; p-value = 0.0072) compared to the non-comorbid group. The accuracy of the anti-RBD test among the PLWH and CKD groups was similar to that among the non-comorbid group but showed lower sensitivity in the SLE group (p = 0.000014). The specificity of the test remained high in all groups. In conclusion, the anti-RBD test had excellent correlation with the sVNT. The persistently high specificity in all groups suggests that this test can be reliably utilized to detect the presence of low neutralization capacity, prompting additional vaccination.

Identification of cytokine signatures in HIV­infected individuals with and without Mycobacterium tuberculosis co­infection.

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-γ, 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-γ release assay. Furthermore, the levels of cytokines IL-17A, IFN-γ, 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™ CD4 assay. IFN-γ, 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/µl, IFN-γ, 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.

Tuberculin skin test and Interferon-gamma release assay agreement, and associated factors with latent tuberculosis infection, in medical and nursing students in Bandung, Indonesia.

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.

Virological failure and drug resistance during first line anti-retroviral treatment in Indonesia.

The virological response and development of drug resistance during first-line anti-retroviral treatment (ART) were studied in Indonesia where the majority of patients infected with HIV have a history of injecting drug use, which is often linked with lower treatment adherence and development of drug-resistance. As many as 575 patients starting ART between September 2007 and March 2010 in Hasan Sadikin Hospital Bandung were followed prospectively. Clinical and laboratory monitoring was performed every 6 months. Plasma samples with HIV-RNA ≥ 400 copies/ml were examined for drug resistance mutations. Most patients were male (72.3%), 59.7% had a history of injecting drug use, and the median CD4+ cells count before start of ART was 35 cells/mm(3) (IQR 10-104). From 438 HIV patients with HIV-RNA measurements, 40 (9.1%) subjects had HIV-RNA ≥ 400 copies/ml after 24 weeks (median follow-up 16 (IQR 8-25) months). Of these failing patients 16 (47%) subjects had drug resistance mutations, predominantly M184V (35.3%), Y181C (23.5%), K103N (11.7%), and TAMs (11.7%). A history of treatment discontinuation ≥ 1 month, reported by 5.3% (23) of patients, was strongly associated with virological failure (adjusted OR 12.64, 95% CI 4.51-35.41); and a history of injecting drug use was not (OR 0.75, 95% CI 0.38-1.46). This is the largest and most systematic evaluation of virological response to first line ART in Indonesia. Patients in this cohort responded well to first line ART, with low rates of virological failure and drug resistance. A history of injecting drug use should not be a reason to withhold ART in this setting.

The Kynurenine/Tryptophan Ratio as a Promising Metabolomic Biomarker for Diagnosing the Spectrum of Tuberculosis Infection and Disease.

The metabolic system and immunology used to be seen as distinct fields of study. Recent developments in our understanding of how the immune system operates in health and disease have connected these fields to complex systems. An effective technique for identifying probable abnormalities of metabolic homeostasis brought on by disease is metabolomics, which is defined as the thorough study of small molecule metabolic intermediates within a biological system that collectively make up the metabolome. A prognostic metabolic biomarker with adequate prognostic accuracy for tuberculosis progression has recently been created. The rate-limiting host enzyme for the conversion of tryptophan to kynurenine, indoleamine 2,3-dioxygenase (IDO), is greatly elevated in the lungs of tuberculosis disease patients. Targeted study on tryptophan in tuberculosis disease indicates that such decreases may also resembled this upregulation. Although tuberculosis diagnosis has improved with the use of interferon release assay and tuberculosis nucleic acid amplification, tuberculosis control is made difficult by the lack of a biomarker to diagnose active tuberculosis disease. We hope that the reader of this work can develop an understanding of the advantages of metabolomics testing, particularly as a sort of testing that can be used for both diagnosing and monitoring a patient's response to treatment for tuberculosis.

Mutation patterns of integrase gene affect antiretroviral resistance in various non-B subtypes of human immunodeficiency virus Type-1 and their implications for patients' therapy.

Although primary integrase strand transfer inhibitor resistance mutations are currently uncommon, the increasing use of integrase strand transfer inhibitor as a key component of the first, second and third-line antiretroviral regimens suggests that the prevalence of integrase drug resistance mutations will likely increase. The rise of several polymorphic mutations and natural polymorphisms also affects the level of susceptibility of human immunodeficiency virus (HIV) type-1 to integrase strand transfer inhibitor. The considerable variability among the various subtypes of human immunodeficiency virus type-1 may contribute to differences in integrase mutations associated with integrase strand transfer inhibitors. Notably, non-B subtypes of HIV type-1 (HIV-1) are the predominant cause of human immunodeficiency virus infection worldwide. The presence of diverse integrase drug resistance mutations can have significant implications on the administration of integrase strand transfer inhibitor-based antiretroviral therapy to patients with human immunodeficiency virus infection.

Detection of Human Herpesviruses in Sera and Saliva of Asymptomatic HIV-Infected Individuals Using Multiplex RT-PCR DNA Microarray.

Human herpesviruses (HHVs) are frequently linked to an increased risk of acquiring human immunodeficiency virus (HIV), and vice versa. This study aimed to detect human herpesvirus (HHV) members in the sera and saliva of asymptomatic HIV-infected individuals. Paired saliva and serum samples were obtained from 30 asymptomatic HIV-infected individuals. HHVs were detected with a multiplex reverse transcription-polymerase chain reaction (RT-PCR) DNA microarray Clart®Entherpex kit. A total of 30 subjects were enrolled: 23 (76.67%) men and 7 (23.33%) women. The present study showed that at least one or more HHV members were detected in the saliva and sera of all (100%) of the subjects. In the saliva, we detected herpes simplex virus 1 (HSV-1) 6.67%, herpes simplex virus 2 (HSV-2) 6.67%, Epstein-Barr virus (EBV) 86.67%, cytomegalovirus (CMV) 63.33%, HHV-6 (40%), and HHV-7 (83.33%). In the sera, HSV-2 (20%), EBV (30%), CMV (40%), HHV-6 (0%), and HHV-7 (76.67%) were found, but not HSV-1. VZV and HHV-8 were not detected in either the saliva or sera. EBV and HHV6 were significantly more prevalent in the saliva than they were in the sera of asymptomatic HIV-infected individuals (p < 0.05). However, no significant differences were found in the prevalence of HSV-1, EBV, CMV, HHV-6, and HHV-7 in the saliva and sera of asymptomatic HIV-infected individuals (p > 0.05). In conclusion, the multiplex RT-PCR DNA microarray can serve as a valuable diagnostic tool that can be used as a screening tool or a first-line test for HHVs infections.

The Association between Vitamin D, Interleukin-4, and Interleukin-10 Levels and CD23+ Expression with Bronchial Asthma in Stunted Children.

Children with stunted growth have an increased risk of wheezing, and studies have shown that low levels of vitamin D and interleukin (IL)-10, along with increased IL-4 levels and CD23+ expression, are present in stunted and asthmatic children. To date, it is not known whether these factors are related to the incidence of asthma in stunted children. This case-control study investigated the association between vitamin D, IL-4, and IL-10 levels and CD23+ expression with bronchial asthma in stunted children. The study included 99 children aged 24-59 months, i.e., 37 stunted-sthmatic children (cases), 38 stunted children without asthma, and 24 non-stunted children with asthma. All children were tested for their 25(OH)D levels using chemiluminescent immunoassay (CLIA), IL-4 and IL-10 levels were measured through enzyme-linked immunosorbent assay (ELISA) testing, and CD23+ expression was measured through flow cytometry bead testing. The data were analyzed using chi-squared, Kruskal-Wallis, and Mann-Whitney tests. The results showed that stunted asthmatic children had a higher incidence of atopic family members than those without asthma. Additionally, stunted asthmatic children had a higher prevalence of vitamin D deficiency (48.6%) than the control group (44.7% and 20.8%). Furthermore, stunted asthmatic children had significantly lower levels of 25(OH)D [20.55 (16.18-25.55), p = 0.042] and higher levels of IL-4 [1.41 (0.95-2.40), p = 0.038], although there were no significant differences in IL-10 levels and CD23+ expression. The study concluded that low vitamin D and high IL-4 levels are associated with bronchial asthma in stunted children, while IL-10 and CD23+ do not show a significant association.

High Positivity Rate of Urinary Mycobacterium tuberculosis Antigens Cocktail (ESAT-6, CFP-10, and MPT-64) in Active Tuberculosis Patients With and Without Human Immunodeficiency Virus Infection: A Cross-Sectional Study.

Introduction: Human immunodeficiency virus (HIV) infection is a risk factor for the occurrence of a large of Mycobacterium tuberculosis (Mtb) antigen load in the body. The antigens cocktail namely early secretory antigenic target protein 6-kDa (ESAT-6), Culture filtrate protein 10 kDa (CFP-10), and Mycobacterium tuberculosis protein 64 (MPT-64) are secreted by Mtb during replication, hence, their concentration increase in patients with active Tuberculosis (TB). This increased levels facilitates their entry into the systemic circulation, followed by secretion by the glomerulus into the urine. The aim of this study was to determine the positivity rate of the urinary Mtb antigens cocktail between TB patients with and without HIV infection. Methods: This is an observational descriptive comparative study conducted with a cross-sectional design. Random urine samples were collected from patients diagnosed with active TB in Dr. Hasan Sadikin Bandung Hospital in 2021. The subjects were divided into 2 groups, TB-HIV group and TB without HIV group. The samples were tested using the quantitative immunochromatography method. Result: Sixty active TB patients consisting of TB patients with HIV infection (n = 30) and TB patients without HIV infection (n = 30). The positivity in the urinary Mtb antigens cocktail was 93.3% for TB-HIV group and 100% for TB without HIV group (P = .492). The median concentration of urinary Mtb antigens cocktail in TB patients without HIV infection was higher than that of TB patients with HIV infection (137.73 ng/mL vs 96.69 ng/mL, respectively; P = .001). Conclusion: There was no significant difference in the positivity rate, meanwhile, there was a significant difference in concentration of the urinary Mtb antigens cocktail between active TB patients with and without HIV infection. Interestingly, this urinary Mtb antigens cocktail can be found in both groups without being affected by the patient's immune condition, thus becoming a test to assist diagnose active TB.

High Levels of Anti-SARS-CoV-2 Receptor-Binding Domain (RBD) Antibodies One Year Post Booster Vaccinations among Hospital Workers in Indonesia: Was the Second Booster Needed?

In August 2022, Indonesia prioritized healthcare workers to receive the second booster dose. We conducted a sequential serosurvey to understand the dynamics of the antibody titers. The first serosurvey, which was conducted in June 2021, 1-6 months after Sinovac vaccination, showed a median antibody level of 41.4 BAU/mL (interquartile range (IQR): 10-629.4 BAU/mL). The second serosurvey was conducted one month (August 2021) after the first Moderna booster vaccine and showed a median level of 4000 BAU/mL (IQR: 3081-4000 BAU/mL). The last serosurvey was conducted a year (August 2022) after the booster and showed a median level of 4000 BAU/mL (IQR: 4000-4000 BAU/mL). In this last survey, only 39 (11.9%) of healthcare workers had antibody levels below the maximum level of 4000 BAU/mL. Thus, one year after the first booster dose, we did not observe the waning of antibody levels. The average increase was perhaps because of natural infection. Based on these considerations, we believe that a second booster dose was not necessary for this category of subjects at that time. Because vaccine supply is often limited, priority could be given to the general population or other high-risk patient groups with low antibody titers based on serological tests.

Performance of a Point-of-Care Fluorescence Immunoassay Test to Measure the Anti-Severe Acute Respiratory Syndrome Corona Virus 2 Spike, Receptor Binding Domain Antibody Level.

Quantitative determination of anti-SARS-CoV2-S-RBD is necessary for the evaluation of vaccination effectiveness. The surrogate viral neutralization test (SVNT) is approved for measuring anti-SARS-CoV2-S-RBD, but a point-of-care platform is needed to simplify anti-SARS-CoV-2-S-RBD measurement. We aimed to evaluate the performance of a rapid fluorescent immunoassay-based kit, FastBio-RBDTM, compared to the SVNT. During April-September 2021, we enrolled two groups of subjects, convalescent subjects and subjects without a COVID-19 history. The subjects were tested for the anti-SARS-CoV2-S-RBD antibody using FastBio-RBDTM and the GenScript-cPASSTM SVNT. We measured the correlation coefficient and conducted an ROC analysis to determine the best cut-off value of anti-SARS-CoV2-S-RBD against the SVNT percent inhibition levels of 30% and 60%. We included 109 subjects. Anti-SARS-CoV-2-S-RBD strongly correlated to SVNT % inhibition with an R value of 0.866 (p < 0.0001). The ROC analysis showed that the anti-SARS-CoV-2-S-RBD of 6.71 AU/mL had 95.7% sensitivity and 87.5% specificity to detect a percentage inhibition of 30%. The anti-SARS-CoV-2-S-RBD of 59.76 AU/mL had a sensitivity of 88.1% and specificity of 97.0% to detect a percentage inhibition of 60%. FastBio-RBDTM could determine the presence and level of anti-SARS-CoV-2-S-RBD with good sensitivity and specificity. It has the potential to be deployed in health facilities with limited resources.