Antibodies against Histoplasma capsulatum and Aspergillus fumigatus among chronic TB patients in Indonesia: a cross-sectional study.

Chronic pulmonary fungal infections may occur in patients with previous history of pulmonary tuberculosis (TB), and are often clinically misclassified as TB, especially when bacteriological confirmation for Mycobacterium tuberculosis is absent. In this study, we investigated the prevalence of antibody against Histoplasma capsulatum and Aspergillus fumigatus in patients with confirmed and clinically chronic TB. Antibodies against H. capsulatum and A. fumigatus were measured from serum samples using enzyme-linked immunosorbent assay (ELISA). The presence M. tuberculosis in sputum was confirmed using smear microscopy, GeneXpert MTB/RIF assay, or culture. Antibodies against H. capsulatum and A. fumigatus were elevated in 16.9% and 26.9% of bacteriologically confirmed chronic TB patients, and 12.1% and 18.2% in those without bacteriological confirmation, respectively. Approximately one-third of patients who had positive anti-Histoplasma antibody also had elevated levels of antibody against Aspergillus fumigatus (P < .001). Our study highlights the importance of chronic pulmonary fungal infection in post-TB patients with recurrent respiratory symptoms.

This study describes the presence of antibodies against Aspergillus fumigatus and Histoplasma capsulatum in patient with pulmonary TB patients. Our study highlights the importance of chronic pulmonary fungal infections in post-TB patients with recurrent respiratory symptoms.

BA.5 sub-lineages associated with higher severity of COVID-19 infection: A cross-sectional study in Indonesia.

Objectives: We aimed to compare the clinical severity and outcome among laboratory-confirmed Omicron variant cases admitted between January and December 2022. Methods: This is a cross-sectional study conducted in Hasan Sadikin General Hospital between January and December 2022. We enrolled patients aged ≥18 years with laboratory-confirmed Omicron infection. Data were collected from clinical records and a whole genome sequencing database. We compared the risk of severe symptoms and mortality using a logistic regression analysis adjusted for sex, age, comorbidities, and vaccination status. Results: We enrolled 255 patients and the main sub-lineages were BA.1 (16.1%), BA.2 (11.4%), BA.5 (35.7%), XBB (22.7%), and BQ.1 (14.1%). Compared with BA.1/BA.2, BA.5 sub-lineages were associated with severe symptoms (adjusted odds ratio of 2.9, 95% confidence interval 1.1-8.2, P <0.05). The highest risk of severe symptoms and mortality was linked with a high number of comorbidities (adjusted odds ratio of 7.8, 95% confidence interval 1.7-22.4, P <0.05). Booster vaccination was protective of severity and mortality. Conclusions: Disease severity was associated with BA.5 sub-lineages and multiple comorbidities. Good management is particularly important for people with comorbidities. Furthermore, booster vaccination is also required to reduce severity and mortality.

Management of drug-resistant tuberculosis in Indonesia: a four-year cascade of care analysis.

Background: In Indonesia, drug resistance testing for TB largely relies on Xpert MTB/RIF, and it is unknown what proportion of drug-resistant (DR) TB is adequately diagnosed and treated. Methods: We conducted a cascade of care analysis on a cohort of presumptive rifampicin-resistant (RR) TB patients registered in 2015-2018 in a tertiary hospital in Indonesia. Estimated incidences of (presumptive) DR-TB cases were assumption-based using global reports. Data on diagnosis and consecutive cascades steps, including their timing were collected from national electronic registers, and medical records. We described a secondary cascade for patients receiving treatment not supported by phenotypic drug susceptibility testing (pDST). Factors associated with delay and loss between diagnosis and treatment were identified using logistic regression. Findings: Less than a third of estimated incident TB cases at risk of DR-TB were identified as presumptive DR-TB case and tested, and 9.8% (982/10,065) of estimated true DR-TB cases was diagnosed. Of those diagnosed, only 45.1% (443/982) had treatment regimens supported by pDST results, but this did not significantly influence treatment outcomes. Only 25.5% (250/982) of diagnosed patients completed all steps of the cascade including successful treatment. Delays between diagnosis and treatment were substantial, and more common among those referred from a primary healthcare facility, and among those who were employed, living outside of Bandung, and reporting engagement with the private sector. Interpretation: The DR-TB care cascade in this urban setting in Indonesia is characterized by substantial attrition and delays. Strategies to increase access to DR-TB diagnosis accompanied by optimisation of clinical care could substantially improve outcomes and reduce onward transmission. Funding: Radboud university medical center and University of Otago.

The Correlation Between sP-Selectin and Platelet Count in COVID-19 Patients in Referral Hospital, West Java Indonesia.

Introduction: sP-selectin is a glycoprotein located in α granules of platelet and endothelial's Weibel Palade body, as expression to platelet activation and endothelial cell stimulation by SARS-CoV-2 binding with ACE2 receptor. Consumptive thrombocytopenia is also related to platelet activation. Elevation of sP-selectin and thrombocytopenia are related to COVID-19 complication and often correlated with severity of COVID-19. Purpose: Assess the correlation between sP-selectin and platelet in COVID-19 patients at intensive care and non-intensive care. Patients and Methods: The study population was hospitalized COVID-19 patients confirmed by Real-Time PCR that underwent platelet examination within 48 hours upon admission, divided into intensive care and non-intensive care group. sP-selectin examination using ELISA methods. Platelet cell count and sP-selectin divided based on normal reference range. Results: The subjects consist of 24 were in intensive care, 25 were in non-intensive care group. A 66.7% of subject in intensive care group has an elevation in sP-selection (>44.0 ng/mL). Thrombocytopenia was significantly correlated with intensive group (r =-0.32, p<0.05). The combination of platelet count <150.000/mm3 and sP-selectin >44.0ng/mL was not correlated with the intensive and non-intensive group. Platelet and sP-selectin were not correlated with each other. Conclusion: Thrombocytopenia is able to induce the expression of sP-selectin.

The Single-Nucleotide Polymorphism (SNP) Validity to Detect Omicron Variants.

Introduction: Mutation of SARS-CoV-2 has generated several variants of concern (VOC) which spread promptly worldwide. These emerging variants affected global strategies to overcome COVID-19. Variants of SARS-CoV-2 are determined by the whole genome sequencing (WGS) assay, which is time-consuming, with limited availability (only in several laboratories). Hence, a faster and more accessible examination is needed. The single-nucleotide polymorphism (SNP) method is one of the options for genomic variation surveillance that can help provide an answer to this challenge. This study aims to determine the validity of the SNP method with PCR to detect omicron variants of SARS-CoV-2 compared with the gold standard, WGS. Methods: This is a diagnostic analysis of 140 confirmed COVID-19 nasopharyngeal samples taken from the Kemayoran COVID Emergency Hospital Laboratory and the West Java Provincial Health Laboratory from April to October 2022. Data analysis was carried out to determine conformity and validity values. Results: Analysis using Cohen's kappa coefficient test showed high conformity between SNP and WGS (p value <0.001; kappa coefficient = 0.948). SNP showed great validity values on omicron BA.1 (90% sensitivity; 100% specificity), omicron BA.2 (100% sensitivity; 99% specificity), and omicron BA.4/5 (99.2% sensitivity; 100% specificity). Conclusion: The SNP method can be a more time-efficient alternative to detect omicron variants of SARS-CoV-2 and distinguish their sublineages (BA.1, BA.2, and BA.4/5) by two different specific gene mutations in combination analysis (ΔH69/V70 and Q493R mutations).

The effect of diabetes mellitus on COVID-19 mortality among patients in a tertiary-level hospital in Bandung, Indonesia.

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.

The Omicron variant of concern: The genomics, diagnostics, and clinical characteristics in children.

Since WHO announced the COVID-19 pandemic in March 2020, SARS-CoV-2 has undergone several mutations, with the most recent variant first identified in South Africa in November 2021, the SARS-CoV-2 variant of concern (VOC B.1.1.529) named by WHO as Omicron. To date, it has undergone more mutations compared to previous SARS-CoV-2 variants, particularly, in the S gene that encodes the spike protein, which can cause S gene target failure in some PCR kits. Since its discovery, the Omicron variant has caused a sharp rise in COVID-19 cases worldwide and was responsible for a record of 15 million new COVID-19 cases reported globally in a single week, although this may be an underestimate. Since January 2022, Omicron subvariants with variable genetic characteristics, BA.1, BA.1.1, BA.2, BA.3, BA.4, BA.5, and BA.2.12.2 have been identified, with several countries reporting BA.1.1 was the major subvariant (27.42%), followed by BA.2 (25.19%). At the begining of May 2022, BA.2.12.1 mostly (42%) was detected in the United States. Like adults, the clinical manifestations of the Omicron variant in children are similar to the previous variants consisting of fever, cough, vomiting, breathing difficulties, and diarrhea, with some reports on croup-like symptoms and seizures. Though it presents apparently milder disease than the Delta variant, it is significantly more contagious and has caused more hospitalizations, especially in unvaccinated children younger than 5 years and unvaccinated or incompletely vaccinated adults. However, there is insufficient evidence yet to distinguish the Omicron variant from the other variants based solely on the clinical manifestations, therefore, this review presents a brief literature review of the most current evidence and data related to Omicron.

Impact of social activity restriction and routine patient screening as a preventive measurement for tertiary referral hospital staff in a country with high COVID-19 incidence.

Background: Measuring COVID-19 incidence among hospital staff and the influencing factors and preventative measures affecting outcomes is important given their high risk of exposure and potential impacts on health service provision. Method: Study participants included all hospital staff with COVID-19 confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) from March 2020 to July 2021. Data were collected on age, gender, occupation, working area, symptoms and vaccination status. We also collected data on pediatric oncology patients and their caregivers to review the hospital screening policy. Results: Approximately 59% of positive cases among hospital staff occurred in the green zone; 75% were fully vaccinated. Whole-genome sequencing indicated that staff infections in June 2021 were Delta variant. A decrease in cases coincided with government implementation of social activity restriction. When RT-PCR was performed in suspected cases, 3 of 36 pediatric oncology patients and 10 staff tested positive. After routine screening, 8 of 121 patients, 3 patient caregivers, and 5 staff tested positive, all were asymptomatic, and all were infected in the community. Conclusions: Routine testing for staff, patients and caregivers, vaccination booster programs, continuing education of health care workers, and government policy, such as social activity restriction, are needed to protect frontline workers.

MDR Pathogens Organisms as Risk Factor of Mortality in Secondary Pulmonary Bacterial Infections Among COVID-19 Patients: Observational Studies in Two Referral Hospitals in West Java, Indonesia.

Purpose: The coronavirus disease (COVID-19) outbreak has created a global health crisis. Secondary pulmonary bacterial infection is a COVID-19 complication, increasing morbidity and mortality. This study aimed to determine the pathogens, antibiotic susceptibility patterns, and risk factors for mortality in hospitalized COVID-19 patients. Patients and Methods: This retrospective study used secondary data from patients' electronic medical records at Hasan Sadikin General Hospital and Santo Borromeus Hospital between March 2020 and March 2021. Overall, 2230 hospitalized COVID-19 patients were screened, and 182 of them who were hospitalized ≥48 hours with a procalcitonin level of ≥0.25 ng/mL were enrolled. Culture examination was performed on sputum samples to determine pathogen and antibiotic susceptibilities. Univariate and multivariate analyses were used to determine mortality-related risk factors in hospitalized COVID-19 patients. Results: The prevalence of secondary pulmonary bacterial infections in COVID-19 patients was 8.2%, with 161/182 pathogen growth from sputum samples. Mainly gram-negative bacteria (64.8%) were present, including Acinetobacter baumannii (31.9%), Klebsiella pneumoniae (19.8%), and Pseudomonas aeruginosa (8.8%). High rate of multidrug-resistant (MDR) pathogens was found among isolate (45.9%), ie carbapenem-resistance A. baumannii (CR-Ab) was 84.2%, extended-spectrum ß-lactamase (ESBL) among K. pneumoniae was 61.1%. Secondary infection of MDR pathogens was associated with a higher risk of mortality (AOR 5.63, p = 0.001). Other associated factors were age ≥60 years, ventilator use, and female gender. Conclusion: Gram-negative bacteria are the predominant pathogens causing secondary pulmonary bacterial infection in COVID-19 patients, implying nosocomial infection. High resistance to first-line antimicrobial drugs was observed in Gram-negative bacteria and Gram-positive bacteria. High rate of MDR pathogens was found among isolate and was associated with a significant risk of mortality.

The performance of point-of-care antibody test for COVID-19 diagnosis in a tertiary hospital in Bandung, Indonesia.

INTRODUCTION: We aim to describe the performance of combined IgM and IgG point-of-care antibody test (POC-Ab) (Wondfo®) compared to real-time reverse transcriptase (rRT-PCR) (Allplex™ 2019-nCoV Assay) in detecting coronavirus disease 2019 (COVID-19). METHODOLOGY: We compared POC-Ab with rRT-PCR results among patients in a tertiary hospital from January to March 2020 in Bandung, Indonesia. We selected presumptive COVID-19 patients with positive rRT-PCR consecutively and 20 patients with negative rRT-PCR results were selected randomly from the same group of patients as controls. We described the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) with corresponding 95% confidence interval using serum and capillary blood samples. We also tested POC-Ab using non-COVID-19 (confirmed dengue and typhoid) patients' sera. RESULTS: Twenty-seven patients with positive rRT-PCR result and 20 negative controls were included (68.1% males, mean age 46 (SD: 15.4)). Using the serum, the sensitivity of the POC-Ab was 63.0% (42.4-80.6), specificity was 95.0% (75.1-99.9), PPV was 94.4% (72.7-99.8), NPV was 65.5% (45.7-82.1). A subset of 20 patients was tested using a capillary blood sample. The accuracy of the capillary blood sample is lower compared to serum (50.0% vs. 78.7%). None of the non-COVID-19 sera tested were reactive. CONCLUSIONS: POC-Ab for COVID-19 has a high specificity with no false-positive result in non-COVID-19 sera. Therefore, it can be used to guide diagnostic among symptomatic patients in resource limited settings. Given its low sensitivity, patients with high suspicion of COVID-19 but non-reactive result should be prioritized for rRT-PCR testing.

Evaluation of Xpert MTB-RIF guided diagnosis and treatment of rifampicin-resistant tuberculosis in Indonesia: A retrospective cohort study.

BACKGROUND: Rifampicin-resistant tuberculosis (RR-TB) is largely underdetected in Indonesia. Xpert MTB/RIF (Xpert) has recently been introduced, prioritizing patients at risk of RR-TB, followed by phenotypic drug-susceptibility (DST) if rifampicin resistance is detected. OBJECTIVE: This study investigated Xpert-based management of presumptive RR-TB cases under routine practice in West Java, Indonesia. METHODS: We examined all records of patients tested with Xpert in the referral hospital for West Java in 2015-2016. We measured loss across a limited cascade of care, time to Xpert diagnosis and the commencement of initial second-line treatment, and identified factors associated with diagnostic and treatment delay. Additionally, we analyzed the appropriateness of treatment according to DST results. RESULTS: Of 3415 patients with presumptive RR-TB, 3215 (94%) were tested by Xpert, of whom 339 (10.5%) were diagnosed as RR-TB. 288 (85%) of 339 RR-TB patients started initial second-line TB treatment, with 48 (14%) patients being lost between diagnosis and pre-treatment assessment. Second-line treatment was commenced at a median of 41 days (IQR 29-70) after RR-TB diagnosis. Delays in both diagnosis and treatment initiation were observed in 104 (52%) of 201 RR-TB patients with identifiable referral date. Rural residence was associated with delay to diagnosis (adjusted OR 2.7; 95%CI 1.5-5.2) and treatment initiation (adjusted OR 2.0; 1.2-3.4). Of 162 patients with available DST result, 107 (66%) had multidrug-resistant tuberculosis (MDR-TB) and 32 (20%) had either pre-extensively drug resistant (pre-XDR) or extensively drug resistant tuberculosis (XDR-TB). We estimated that with the current algorithm 41% of pre-XDR or XDR-TB patients are diagnosed, and 33% of them started on an appropriate treatment regimen. CONCLUSIONS: Many patients with Xpert-diagnosed RR-TB either do not start MDR-TB treatment or encountered diagnostic and treatment delays under programmatic conditions in Indonesia, and most pre-XDR and XDR-TB cases remain undiagnosed. Further expansion and ongoing quality improvement of RR-TB services are urgently needed.