Histoplasma antigen detection in unconfirmed pulmonary tuberculosis and cross-reactivity with Aspergillus antigen in patients and in food in Jakarta, Indonesia.

PURPOSE: H. capsulatum is endemic in Indonesia, but the value of Histoplasma antigen detection has not been studied. PATIENTS AND METHODS: Histoplasma galactomannan (GM) ELISA was applied to sera of patients with unproven pulmonary tuberculosis (TB) and patients with a positive Aspergillus GM. Both Histoplasma and Aspergillus GM tests were performed to determine any possible cross-reaction with certain foods. RESULTS: Fourteen of 122 (11.5%) sera of patients with newly diagnosed clinical TB were positive for Histoplasma GM. The positivity rate in the serum of patients 5-6 and 12 months after TB diagnosis was 3.8% and 3.5%, respectively. Of 88 positive Aspergillus GM sera, 63 (71.6%) were also positive for Histoplasma GM. All tested foods were positive for Aspergillus GM, while 65% of foods were positive for Histoplasma GM. CONCLUSION: Galactomannan is widespread in sera and food in Jakarta, possibly related to food consumption. Histoplasma and Aspergillus antigen detection for the diagnosis will require additional means of confirming the diagnosis; negative tests may be more helpful for ruling out invasive histoplasmosis and aspergillosis.

The Antifungal Activities of Syzygium aromaticum and Alpinia purpurata Extracts Against Candida krusei: Bioactivity Tests, Molecular Modeling, and Toxicity Tests.

BACKGROUND: Candida krusei is the cause of the fungal infection candidiasis, which has a high mortality rate. Intrinsic resistance to fluconazole can cause the failure of Krusei candidiasis treatment. Therefore, it is necessary to find alternative drugs to eliminate the fungus. Extracts of Syzygium aromaticum and Alpinia purpurata have been proven to be alternative solutions for treating Candida krusei resistance. OBJECTIVE: This study aims to explore the active compounds Syzygium aromaticum and Alpinia purpurata as treatments against Candida krusei through bioactivity tests, molecular modeling, and toxicity tests. METHODS: Determination of antifungal activity with the agar well diffusion and microbroth dilution method. Molecular modeling was conducted using the following software: Marvin Sketch, LigandScout  4.4.5, AutoDock ver 4.2.6, PyMOL, LigPlus, MOE ver 2008. RESULT: Bioactivity test results of the two natural extracts against C. krusei ATCC 6258, it was found that the S. aromaticum and A. purpurata extracts have MIC50 values of 0.031 µg/mL and 1.435x105 µg/mL. The molecular modeling found that the compounds Benzotriazole, 1-(4-methyl-3-nitrobenzoyl)-, 1,3,4-Eugenol Acetate, Stigmasta-5,22-dien-3-ol, acetate (3 beta)- and Farnesyl acetate from the two natural extracts, interacts with the active site of the enzyme lanosterol-14-α-demethylase with a binding energy of -8.91, -6.04, -13.53, and -7.15 kcal/mol. The oral acute toxicity test of S. aromaticum and A. purpurata extracts proved that the LD50 was >6000 mg/kg BW and >8000 mg/kg BW. The acute dermal toxicity test of the two extracts showed that the LD50 was >6000 mg/kg BW. CONCLUSION: S. aromaticum and A. purpurata extracts have been proven to be alternative solutions for treating Candida krusei resistance.

The Fungal and Bacterial Interface in the Respiratory Mycobiome with a Focus on Aspergillus spp.

The heterogeneity of the lung microbiome and its alteration are prevalently seen among chronic lung diseases patients. However, studies to date have primarily focused on the bacterial microbiome in the lung rather than fungal composition, which might play an essential role in the mechanisms of several chronic lung diseases. It is now well established that Aspergillus spp. colonies may induce various unfavorable inflammatory responses. Furthermore, bacterial microbiomes such as Pseudomonas aeruginosa provide several mechanisms that inhibit or stimulate Aspergillus spp. life cycles. In this review, we highlighted fungal and bacterial microbiome interactions in the respiratory tract, with a focus on Aspergillus spp.

Pneumocystis jirovecii colonization in bronchoalveolar lavage among naïve non-small cell lung cancer from tertiary respiratory hospital in Jakarta, Indonesia.

INTRODUCTION: Pneumocystis jirovecii pneumonia (PJP) is a lung mycosis commonly found in immunocompromised patients (e.g., HIV patients); however, its role in solid cancer remains unclear. This study aims to identify Pneumocystis jirovecii colonization among naïve non-small-cell lung cancer (NSCLC) through bronchoalveolar lavage (BAL) and explore its correlation with clinical parameters. METHODOLOGY: This cross-sectional study recruited newly diagnosed naïve NSCLC patients who had not been given systemic treatments. We tested BAL from patients for P. jirovecii colonization with nested PCR targeting the mtLSU rRNA gene. Demographic and clinical characteristics were obtained from medical records, and the correlation between P. jirovecii colonization and clinicopathological data were analyzed. Kaplan-Meier analyses were done to evaluate survival. RESULTS: Among 56 newly diagnosed, naïve NSCLC patients enrolled, the prevalence of P. jirovecii colonization was 17.9% (10 subjects). There was no statistically significant difference in demographic and clinical characteristics between the P. jirovecii colonization group versus no colonization (p value > 0.05). The overall survival duration for both groups demonstrated no significant difference. CONCLUSIONS: This study demonstrated a relatively high prevalence of P. jirovecii colonization among BAL samples of naïve Indonesian NSCLC patients. Further study is needed to delineate its implications for the potential transmission source, lung cancer pathogenesis, and prognosis.

Low-cost SYBR Green-based RT-qPCR assay for detecting SARS-CoV-2 in an Indonesian setting using WHO-recommended primers.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for the ongoing coronavirus disease 2019 (COVID-19) pandemic. For laboratory diagnosis, low-cost detection of SARS-CoV-2 is urgently needed, particularly in developing countries with limited resources. Probe- or TaqMan-based real-time reverse transcription polymerase chain reaction (RT-qPCR) is currently the gold standard for diagnosing infected individuals, as recommended by the World Health Organization (WHO). However, this assay is expensive, making it difficult to use for diagnosis on a large scale. Therefore, in this study, we develop and validate an alternative approach for RT-qPCR diagnosis by employing the DNA intercalating dye SYBR Green. We evaluate and use two WHO-recommended primers, namely CCDC-N and HKU-ORF1b-nsp14. The compatibility of the two primers was tested in silico with Indonesian SARS-CoV-2 genome sequences retrieved from the GISAID database and using bioinformatic tools. Using in vitro-transcribed RNA, optimization, sensitivity, and linearity of the two assays targeting the N and Nsp-14 genes were carried out. For further evaluation, we used clinical samples from patients and performed the SYBR Green-based RT-qPCR assay protocol in parallel with TaqMan-based commercial assay. Our results show that our methodology performs similarly to the broadly used TaqMan-based detection method in terms of specificity and sensitivity and thus offers an alternative assay for the detection of SARS-CoV-2 RNA for diagnostic purposes.

Unravelling the Molecular Identification and Antifungal Susceptibility Profiles of Aspergillus spp. Isolated from Chronic Pulmonary Aspergillosis Patients in Jakarta, Indonesia: The Emergence of Cryptic Species.

Cryptic species of Aspergillus have rapidly increased in the last few decades. Chronic pulmonary aspergillosis (CPA) is a debilitating fungal infection frequently affecting patients with previous TB. The identification and antifungal susceptibility profiles of different species of Aspergillus are important to support the management of CPA. The aim of this study was to describe the molecular and susceptibility profiles of Aspergillus isolated from CPA patients. The species identity of isolates was determined by combined DNA analyses of internal transcribed space (ITS), partial ß-tubulin genes, and part of the calmodulin gene. We revealed a high (27%) prevalence of cryptic species among previous tuberculosis patients with persistent symptoms. Twenty-nine (49%) patients met the criteria for diagnosis of CPA with 24% containing Aspergillus cryptic species. This is the first report of five cryptic Aspergillus species from clinical isolates in Indonesia: A. aculea tus, A. neoniger, A. brunneoviolacues, A. welwitschiae, and A. tubingensis. Significantly, there was decreased sensitivity against itraconazole in the CPA group (66% susceptible to itraconazole) compared to the non-CPA group (90% susceptible to itraconazole) (p = 0.003). The species-level characterisation of Aspergillus and its antifungal susceptibility tests demands greater attention to better the management of CPA patients.

A New Filter Based Cultivation Approach for Improving Aspergillus Identification using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS).

Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) is widely used in clinical laboratories for routine identification of bacteria and yeasts. However, methodological difficulties are still apparent when applied to filamentous fungi. The liquid cultivation method recommended by Bruker Daltonics GmbH for identification of filamentous fungi by MALDI-TOF MS is labour intensive and time-consuming. In this study, growth of Aspergillus species on different (porous) surfaces was investigated with the aim to develop a more reliable, quicker and less laborious identification method using MALDI-TOF MS. Mycelial growth without sporulation mimicking liquid cultivation and reliable MALDI-TOF MS spectra were obtained when A. fumigatus strains were grown on and in between a polycarbonate membrane filter on Sabouraud dextrose agar. A database of in-house reference spectra was created by growing Aspergillus reference strains (mainly focusing on sections Fumigati and Flavi) under these selected conditions. A test set of 50 molecularly identified strains grown under different conditions was used to select the best growth condition for identification and to perform an initial validation of the in-house database. Based on these results, the cultivation method on top of a polycarbonate filter proved to be most successful for species identification. This method was therefore selected for the identification of two sets of clinical isolates that mainly consisted of Aspergilli (100 strains originating from Indonesia, 70 isolates from Qatar). The results showed that this cultivation method is reliable for identification of clinically relevant Aspergillus species, with 67% and 76% correct identification of strains from Indonesia and Qatar, respectively. In conclusion, cultivation of Aspergilli on top of a polycarbonate filter showed improved results compared to the liquid cultivation protocol recommended by Bruker in terms of percentage of correct identification, ease of MSP creation, time consumption, cost and labour intensity. This method can be reliably applied for identification of clinically important Aspergilli and has potential for identification of other filamentous fungi.

Whole genome sequencing data of Candida krusei, the pathogen causing Candidaemia, from Department of Parasitology Culture Collection, Faculty of Medicine Universitas Indonesia.

Candida krusei is a Candida non-albicans species with a high prevalence, which causes candidaemia. Current treatment guidelines include fluconazole as a primary therapeutic option for the treatment of these infections; however, it is only a fungistatic against Candida spp., and both inherent and acquired resistance to fluconazole have been reported. C. krusei species is also reported as the only Candida sp. which has an intrinsic resistance factor to fluconazole. Therefore, in dealing with antifungal resistance, it is necessary to develop new antifungal agents that are efficient in the treatment of fungal infections, especially those caused by C. krusei. The purpose of this study was to investigate the genome of clinical C. krusei isolates and correlate the resistant phenotypes with mutations in resistance genes. A total of 16 samples of C. krusei from clinical samples from hospitals in Jakarta were used in the experiment. All colonies were extracted using the QIAamp DNA Mini Kit. The library was prepared using the Illumina DNA Prep Kit. The sequencing process was carried out on the Illumina MiSeq Platform using a 2x301 paired-end configuration. FASTQ raw files are available under the BioProject Accession Number PRJNA819536 and Sequence Read Archive Accession Numbers SRR18739949 and SRR18739964.

A prospective longitudinal study of chronic pulmonary aspergillosis in pulmonary tuberculosis in Indonesia (APICAL).

OBJECTIVES: Chronic pulmonary aspergillosis (CPA) can complicate recovery from pulmonary TB. CPA may also be misdiagnosed as bacteriologically negative TB. This study aimed to determine the incidence of CPA in patients treated for TB in Indonesia, a country with a high incidence of TB. METHODS: In this prospective, longitudinal cohort study in patients treated for pulmonary TB, clinical, radiological and laboratory findings were analysed. Sputum was collected for fungal culture and TB PCR. Patients were assessed at baseline (0-8 weeks) and at the end (5-6 months) of TB therapy. CPA diagnosis was based on symptoms (≥3 months), characteristic radiological features and positive Aspergillus serology, and categorised as proven, probable and possible. RESULTS: Of the 216 patients recruited, 128 (59%) were followed up until end of TB therapy. At baseline, 91 (42%) had microbiological evidence for TB. Aspergillus-specific IgG was positive in 64 (30%) patients and went from negative to positive in 16 (13%) patients during TB therapy. The incidence rates of proven and probable CPA at baseline were 6% (n=12) and 2% (n=5) and end of TB therapy 8% (n=10) and 5% (n=7), respectively. Six patients (two with confirmed TB) developed an aspergilloma. Diabetes mellitus was a significant risk factor for CPA (p=0.040). Persistent cough (n=5, 50%; p=0.005) and fatigue (n=6, 60%; p=0.001) were the most common symptoms in CPA. CONCLUSION: CPA should be considered a relatively frequent differential diagnosis in patients with possible or proven TB in Indonesia. Lack of awareness and limited access to Aspergillus-specific IgG tests and CT imaging are obstacles in establishing a CPA diagnosis.

Bronchoscopy Findings of Severe and Critical COVID-19 Patients Treated in ICU: A Year of Experience in a Developing Country.

Background: Bronchoscopy procedure in patients with COVID-19 poses significant challenges, especially in a developing country with limited resources. Objectives: We aim to describe the clinical characteristics of severe and critical COVID-19 patients treated in an intensive care unit (ICU) and their bronchoscopy findings. Methods: We performed a retrospective analysis of clinical data of ICU patients with COVID-19 treated and received bronchoscopy procedures. This study retrospectively included all consecutive patients who underwent bronchoscopy at a teaching hospital in Depok, Indonesia, from May, 2020, until May, 2021. Results: A total of 57 bronchoscopy procedures in 54 patients were performed in this study. Primary procedure indications were retained mucus (68.4%) and ventilatory support weaning failure (15.8%). Bronchoscopic findings were mostly hyperaemic mucosa (95.00%) and purulent secretion (50.90%). Microbiological findings from bronchoalveolar samples were Acinetobacter baumanii, Klebsiella pneumoniae, and Candida albicans (33.3%, 26.6%, and 10.5%, respectively). The most common fungal isolated were Candida albicans (28%), followed by Candida tropicalis (16%) and Aspergillus sp. (8%). The overall length of hospital stay was 24 days, and the in-ICU stay was 22.06 ± 10.99 days. The patients' survival of 28-days postprocedural outcome was 25.9% (14 subjects). Follow-up found that 20.4% of patients survived after sixty days of hospitalization. Conclusion: Diagnostic and therapeutic bronchoscopy in ICU patients with COVID-19 was safe and feasible to perform in developing countries with limited resources. It could help bronchial mucous clearance and confirm microbiological infection. The procedures should be strictly performed for patients with indications and comply with safety standards.

The effect of repeated education using live demonstrations and videos of how to use inhalation drugs on quality of life for COPD patients.

Repeated education regarding the proper use of inhalers can reduce the error rate in inhaler-using patients and improve COPD patients' quality of life. This study investigates the effect of repeated education on the quality of life of COPD patients during the pandemic of COVID-19 from February to June 2020. Repeated education is provided using direct demonstrations to patients through educational media in the form of short videos made by the researchers for each inhaler type. This is a pre-experimental study design which was carried out prospectively at Grha Permata Ibu Hospital, Depok. The quality of life of 22 subjects was examined using the COPD assessment test (CAT) questionnaire. Each patient was given a direct verbal demonstration of the appropriate use of the inhaler. One month later, each patient was provided further education using less than 2 min of video sent to them online via the WhatsApp application. Final quality-of-life examination and assessment of inhaler technique were carried out three months after the initial examination. Assessment of proper inhaler technique was carried out using a specific checklist regarding the use of inhaler translated by the researcher. Before and after delivery of repeated education, the mean CAT score showed a decrease of two points, i.e., 12.8 ± 1.3 and 10.8 ± 2.0, respectively. This indicated that quality of life of the patients had significant improvement. However, as many as 63.6% of patients still made mistakes in using inhaler even though they had been educated. For DPI-type inhalers, mistake mostly happened at step "breath out gently, away from inhaler". For pMDI-type inhalers, mistake mostly happened at step "while holding breath, remove inhaler from mouth". It can be concluded that repeated education regarding proper inhaler technique with direct demonstrations and further maintained by videos can improve the quality of life in COPD patients.

Molecular typing and antifungal susceptibility study of Aspergillus spp. in intensive care unit (ICU) patients in Indonesia.

INTRODUCTION: Aspergillus exhibits a wide variation of susceptibility against antifungals according to genetic and environmental factors. Identification to the species level is necessary for appropriate treatment. Our objective was to determine the Aspergillus species involved in invasive pulmonary aspergillosis (IPA) among ICU patients in Jakarta, Indonesia. METHODOLOGY: The incidence of IPA in ICU patients at six hospitals in Jakarta from October 2012 - January 2015 was investigated. It involved a collection of endotracheal aspirates (ETA), nasal swabs and environmental samples around the hospitals, phenotypic screening, molecular characterization, and antifungal susceptibility testing. RESULTS: Of the 405 patients investigated, 31 patients (7.7%) were diagnosed with putative IPA, from whom 45 Aspergillus isolates were collected. Aspergillus isolates were identified from pulmonary secretions in 24 patients, from nasal swabs in 7 patients and from both pulmonary secretions and nasal swabs in 7 patients. The phenotypic method showed 33 isolates of Aspergillus flavus (73.4%), nine Aspergillus fumigatus (20%), two Aspergillus niger (4.4%), and one Aspergillus nidulans (2.2%) isolate. Molecular identification showed 27 isolates of A. flavus (60.0%), eight isolates of A. fumigatus (17.8%), two isolates of A. niger (4.4%) and one isolate of A. nidulans (2.2%), while seven isolates (15.6%) were cryptic species or mixed isolates. CONCLUSIONS: Susceptibility testing showed all isolates were susceptible to amphotericin B, azoles and micafungin. Aspergillus flavus was the main causative organism in IPA cases in Jakarta, followed by A. fumigatus.

Glutathione (GSH) and superoxide dismutase (SOD) levels among junior high school students induced by indoor particulate matter 2.5 (PM2.5) and nitrogen dioxide (NO2) exposure.

BACKGROUND: Indoor air pollution has globally known as the risk factor of acute respiratory infection in young children.  The exposure to indoor particulate matter 2.5 (PM2.5) and nitrogen dioxide (NO2) at house or school can be a potential risk to children's health. This study aimed to examine the association between indoor PM2.5 and NO2 with oxidative stress markers in junior high school students. DESIGN AND METHOD: This study was conducted using a cross sectional study with 75 students collected randomly from four junior high schools in Jakarta.  PM2.5 and NO2 were measured in classrooms and school yards. The schools were categorized based on the exposure level of PM2.5 and NO2 in classrooms. Superoxide dismutase (SOD) and reduced glutathione (GSH) were examined from the blood sample. All students were interviewed with questionnaires to determine upper respiratory tract infection, smoking family members, mosquito repellent usage, and dietary supplement consumption. RESULTS: Mean concentration of indoor PM2.5 and NO2 were 0.125±0.036 mg m-3 and 36.37±22.33 µg m-3, respectively. The schools which located near to highway showed lower PM2.5 and higher NO2 level indicated the emission of traffic activity. Mean activity of SOD was 96.36±50.94 U mL-1 and mean concentration of GSH was of 0.62±0.09 µg mL-1. Most of the students reported upper respiratory tract infection history, smoking family member, use mosquito repellent at home, and do not consume dietary supplement. CONCLUSION: The level of oxidative stress markers and the exposure categories of classroom PM2.5 and NO2 was not significantly different, however there were significant correlation with cigarette smoke and mosquito repellent at home. Nevertheless, the exposure of indoor PM2.5 and NO2 increased the risk of the exposure to cigarette smoke and mosquito repellent at home. Further study on the air pollution at school and home is needed to affirm association towards student's health and to design strategic control efforts.

Serious fungal disease incidence and prevalence in Indonesia.

BACKGROUND: Indonesia is a tropical country, warm and humid, with numerous environmental fungi. Data on fungal disease burden help policymakers and clinicians. OBJECTIVES: We have estimated the incidence and prevalence of serious fungal diseases. METHODS: We found all published and unpublished data and estimated the incidence and prevalence of fungal diseases based on populations at risk. HIV data were derived from UNAIDS (2017), pulmonary tuberculosis (PTB) data from 2013-2019, data on chronic pulmonary aspergillosis (CPA) were used to estimate CPA prevalence and likely deaths, COPD data from Hammond (2020), lung cancer incidence was from Globocan 2018, and fungal rhinosinusitis was estimated using community data from India. RESULTS: Overall ~7.7 million Indonesians (2.89%) have a serious fungal infection each year. The annual incidence of cryptococcosis in AIDS was 7,540. Pneumocystis pneumonia incidence was estimated at 15,400 in HIV and an equal number in non-HIV patients. An estimated 1% and 0.2% of new AIDS patients have disseminated histoplasmosis or Talaromyces marneffei infection. The incidence of candidaemia is 26,710. The annual incidence of invasive aspergillosis was estimated at 49,500 and the prevalence of CPA is at 378,700 cases. Allergic bronchopulmonary aspergillosis prevalence in adults is estimated at 336,200, severe asthma with fungal sensitisation at 443,800, and fungal rhinosinusitis at 294,000. Recurrent vulvovaginal candidiasis is estimated at 5 million/year (15-50 years old). The incidence of fungal keratitis around 40,050. Tinea capitis prevalence in schoolchildren about 729,000. CONCLUSIONS: Indonesia has a high burden of fungal infections.

Performance of LDBio Aspergillus WB and ICT Antibody Detection in Chronic Pulmonary Aspergillosis.

The detection of Aspergillus antibody has a key role in the diagnosis of chronic pulmonary aspergillosis. Western blot (WB) and immunochromatography (ICT) lateral flow detection of Aspergillus antibody can be used as confirmatory and screening assays but their comparative performance in TB patients is not known. This study investigated the performance of these assays among 88 post-tuberculosis patients with suspected CPA. Sensitivity, specificity, receiver operating curve (ROC), area under-curve (AUC) and the agreement between two assays were evaluated. Both WB and ICT showed good sensitivity (80% and 85%, respectively) for detection of Aspergillus antibodies. Substantial agreement (0.716) between these assays was also obtained. The highest AUC result (0.804) was achieved with the combination of WB and ICT. The global intensity of WB correlated with the severity of symptoms in CPA group (p = 0.001). The combination of WB and ICT may increase specificity in CPA diagnosis.

Chronic Pulmonary Aspergillosis in Post Tuberculosis Patients in Indonesia and the Role of LDBio Aspergillus ICT as Part of the Diagnosis Scheme.

Chronic pulmonary aspergillosis (CPA) is a common sequela of pulmonary tuberculosis (TB). The diagnosis of CPA is difficult and often misdiagnosed as smear-negative TB in endemic settings. Aspergillus IgG detection is the cornerstone of CPA diagnosis. There are a lack of studies on the prevalence of CPA in GeneXpert/smear-negative TB patients in Indonesia, despite a high number of TB cases. This study aims to determine the CPA rate in HIV-negative, GeneXpert-negative patients presenting with symptoms following completion of TB therapy and to evaluate the performance of LDBio Aspergillus immunochromatographic technology (ICT) lateral flow assay in the diagnosis of CPA. CPA was diagnosed on the basis of symptoms for ≥3 months, characteristic chest imaging and positive Aspergillus culture. Twenty (22%) out of 90 patients met the criteria for CPA. The LDBio test was positive in 16 (80%) CPA patients and in 21 (30%) non-CPA patients (p < 0.001) with 80% sensitivity and 70% specificity. Logistic regression revealed a positive LDBio Aspergillus ICT result, smoking history and diabetes to be important predictors of CPA diagnosis. Although CPA is an unrecognised disease in Indonesia, this study suggests that more than one in five GeneXpert negative patients with persistent symptoms following completion of TB therapy may have CPA.

Factors Associated with Death in COVID-19 Patients in Jakarta, Indonesia: An Epidemiological Study.

BACKGROUND: Coronavirus Disease 2019 is an emerging respiratory disease that is now a pandemic. Indonesia is experiencing a rapid surge of cases but the local data are scarce. METHODS: this is an analysis using data from the ongoing recapitulation of Epidemiological Surveillance (ES) by the Provincial Health Office of Jakarta from March 2nd to April 27th 2020. We evaluated demographic and clinical characteristics of all confirmed cases in association with death. RESULTS: of the 4,052 patients, 381 (9.4%) patients were deceased. Multivariable analysis showed that death was associated with older age (odds ratio [OR] 1.03; 95% confidence interval [CI] 1.02, 1.05, per year increase; p<0.001), dyspnea (OR 4.83; 95% CI 3.20, 7.29; p<0.001), pneumonia (OR 2.46; 95%CI 1.56, 3.88; p<0.001), and pre-existing hypertension (OR 1.86; 95% CI 1.24, 2.78; p=0.003). Death was highest in the week of April 6th 2020 and declined in the subsequent weeks, after a large-scale social restriction commenced. CONCLUSION: older age, dyspnea, pneumonia, and pre-existing hypertension were associated with death. Mortality was high, but may be reduced by lockdown.

Therapeutic response time of topical voriconazole 1% and intrastromal voriconazole 0.05% versus topical natamycin 5% monotherapy in Fusarium keratitis in rabbit.

BACKGROUND: Fungal keratitis can be more difficult to treat than bacterial keratitis with worse outcomes. OBJECTIVE: To evaluate the therapeutic response time of topical voriconazole combined with intrastromal voriconazole, and topical natamycin on Fusarium keratitis. METHODS: The stroma of corneas of twelve New Zealand White rabbits was inoculated with Fusarium sp spores. Seven days after inoculation, they were divided into 2 groups randomly. Group A was treated with topical natamycin 5% for 21 days. Group B was treated with intrastromal voriconazole 0.05% single injection at the beginning of treatment, continued with topical voriconazole 1% for 21 days. Clinical evaluations for epithelial defect size and clinical scores in each group were performed on 1st, 3rd, 7th, 10th, 14th and 21st days after treatment. Mycological examinations were performed before and after the treatment. RESULTS: After treatment, there was no statistically significant difference between natamycin and voriconazole in reducing epithelial defect size at first, second or third week after treatment (P = .15; P = .39; and P = .90). The clinical scores on both groups also showed no statistically significant differences at first, second and third weeks after treatment (P = .24; P = .09; and P = .32). Qualitative mycological evaluation before and after the treatment showed no statistically significant difference in KOH examination (P = 1; P = 1) and culture in Sabouraud dextrose agar (P = 1; P = 1). CONCLUSION: Intrastromal voriconazole injection combined with topical voriconazole seems to give similar response time but not earlier in improving clinical presentation of Fusarium keratitis as topical natamycin.

Evaluation and comparison of automated and manual ELISA for diagnosis of chronic pulmonary aspergillosis (CPA) in Indonesia.

Pulmonary tuberculosis (TB) is one of the common risk factors for chronic pulmonary aspergillosis (CPA). A positive Aspergillus IgG is a key element of the diagnosis of CPA but this has not been studied in Indonesia. We conducted studies with patients at the end of TB therapy in Indonesia. We performed receiver operating curve (ROC) analysis to determine the optimum cutoff of the Aspergillus-specific IgG level (Immulite and Dynamiker ELISA) in those patients who met criteria of CPA in relation to control groups. In 203 TB patients, 26 (13%) patients had clinical and radiological features of CPA. We derived optimum cutoffs for Immulite Aspergillus-specific IgG of 11.5 mg/L and Dynamiker anti-galactomannan IgG of 106.8 AU/mL (sensitivity 89% and 83%, specificity 78% and 51%, respectively). The currently accepted Aspergillus-specific IgG cutoff of Immulite and Dynamiker assays for CPA diagnosis may require slight adjustment for the Indonesian population.

Chronic Pulmonary Histoplasmosis-A Scoping Literature Review.

Chronic pulmonary histoplasmosis (CPH) is an uncommon manifestation of Histoplasma infection with features similar to pulmonary tuberculosis (TB). In endemic areas, it may be misdiagnosed as smear-negative pulmonary TB. Historical case series mainly from patients with presumed TB described a high frequency of cavitation and poor prognosis, likely resulting from delayed presentation. More recent reports suggest that CPH can present with nodules, lymphadenopathy, or infiltrates, with cavities being a less common feature. Emphysema is the main risk factor for cavitary CPH. CPH is therefore an umbrella term, with chronic cavitary pulmonary histoplasmosis and Histoplasma nodules being the main long-term manifestations in nonimmunocompromised individuals. Diagnosis relies on a high index of suspicion, use of fungal culture of respiratory samples, antibody testing, and compatible radiological picture. Treatment with itraconazole for at least 12 months is recommended. Morbidity from CPH results from slow progression of cavities and gradual loss of lung function, especially if not recognized and treated. Studies on the epidemiology of CPH are needed in order to improve understanding of the disease.