Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM).

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

Risk factors, mortality, and predictors of survival in COVID-19-associated pulmonary mucormycosis: a multicentre retrospective study from India.

OBJECTIVES: To compare COVID-19-associated pulmonary mucormycosis (CAPM) with COVID-19-associated rhino-orbital mucormycosis (CAROM), ascertain factors associated with CAPM among patients with COVID-19, and identify factors associated with 12-week mortality in CAPM. METHODS: We performed a retrospective multicentre cohort study. All study participants had COVID-19. We enrolled CAPM, CAROM, and COVID-19 subjects without mucormycosis (controls; age-matched). We collected information on demography, predisposing factors, and details of COVID-19 illness. Univariable analysis was used to compare CAPM and CAROM. We used multivariable logistic regression to evaluate factors associated with CAPM (with hypoxemia during COVID-19 as the primary exposure) and at 12-week mortality. RESULTS: We included 1724 cases (CAPM [n = 122], CAROM [n = 1602]) and 3911 controls. Male sex, renal transplantation, multimorbidity, neutrophil-lymphocyte ratio, intensive care admission, and cumulative glucocorticoid dose for COVID-19 were significantly higher in CAPM than in CAROM. On multivariable analysis, COVID-19-related hypoxemia (aOR, 2.384; 95% CI, 1.209-4.700), male sex, rural residence, diabetes mellitus, serum C-reactive protein, glucocorticoid, and zinc use during COVID-19 were independently associated with CAPM. CAPM reported a higher 12-week mortality than CAROM (56 of the 107 [52.3%] vs. 413 of the 1356 [30.5%]; p = 0.0001). Hypoxemia during COVID-19 (aOR [95% CI], 3.70 [1.34-10.25]) and Aspergillus co-infection (aOR [95% CI], 5.40 [1.23-23.64]) were independently associated with mortality in CAPM, whereas surgery was associated with better survival. DISCUSSION: CAPM is a distinct entity with a higher mortality than CAROM. Hypoxemia during COVID-19 illness is associated with CAPM. COVID-19 hypoxemia and Aspergillus co-infection were associated with higher mortality in CAPM.

Basidiobolomycosis caused by a rare species - Basidiobolus meristosporus.

A five-year girl was referred to our centre with swelling over the right lower back. The child was evaluated to rule out chronic cutaneous tuberculosis, lymphoma and soft tissue tumor. Biopsy of the lesion on culture yielded Basidiobolus species. Whole genome sequencing of the isolate identified it as Basidiobolus meristosporus. Sequencing of fungi pathogenic to humans which cannot be differentiated by conventional methods of speciation becomes essential to assign pathogenicity, understand epidemiology and resolve the nuances in the ever-evolving taxonomical classification.

A simple high-volume culture technique-Good substitute for polymerase chain reaction for the detection of Aspergillus species in bronchoalveolar lavage samples.

BACKGROUND: Aspergillus species is the most common agent of invasive pulmonary fungal disease. Culture-based diagnosis considered as gold standard is limited by the fungal load in samples. Detection of Aspergillus by polymerase chain reaction (PCR) has been included as a diagnostic criterion by European Organisation for Research and Treatment of Cancer (EORTC). Most routine laboratories lack facilities for molecular diagnosis. Better yield using high-volume culture (HVC) technique has been reported. Studies have not compared HVC and PCR for detection of Aspergillus species in respiratory samples from patients with suspected invasive pulmonary Aspergillosis (IPA) not on antifungal therapy. OBJECTIVE: This pilot study compared HVC and PCR for the detection of Aspergillus species in respiratory samples from treatment naïve patients. METHODS: Bronchoalveolar lavage (BAL) samples from 30 patients with clinical suspicion of IPA were evaluated. Direct microscopy, culture both conventional (CC) and HVC and qualitative Pan Aspergillus PCR were performed. Latent class model was used for statistical analysis. RESULTS: Sensitivity of HVC (100%) was better compared with CC (60%) and comparable to that of PCR (100%). Specificities of CC, HVC and PCR were 100%, 100% and 25%, respectively. CONCLUSION: High-volume culture is a simple cost-effective technique with a high sensitivity and specificity. It can be easily introduced in routine microbiology laboratories. In centres with the availability of infrastructure for molecular analysis, Aspergillus PCR with other mycological techniques can be used for better diagnosis and management of patients with IPA.

Case of melioidosis misdiagnosed as pulmonary tuberculosis.

Melioidosis is an endemic infection caused by Burkholderia pseudomallei predominantly reported in the coastal parts of India. A 19-year-old male student with no comorbidities presented with features suggestive of pneumonia. He was initiated on antitubercular treatment empirically elsewhere. However, due to lack of response to therapy diagnosis was revisited. Microbiological investigations were unyielding initially. Despite antitubercular treatment, he presented with complications of pneumonia and was diagnosed to have melioidosis. He was initiated on appropriate antibiotics for the intensive and eradication phase. Obtaining microbiological confirmation is of utmost importance to prevent misdiagnosis and undue morbidity and mortality due to these uncommon infections.

A simple x-ray scoring system for the diagnosis of chronic pulmonary aspergillosis.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) is a severe form of post-tuberculosis lung disease (PTBLD). Considering the high burden of TB in India, it can be concluded that the prevalence of CPA is also high. Chest x-ray though most feasible, interpretation is subjective. Therefore, decision on evaluation for CPA cannot be based on x-ray alone. OBJECTIVE: Present study evaluated an x-ray score as a marker for extent of lung damage in patients with PTBLD presenting with haemoptysis and its utility to predict Aspergillus serum IgG levels. METHODS: We used a modified scoring system developed by Anna Ralph et al X-ray score cut-offs of >71 and 40, with or without history of massive haemoptysis, were compared with serum IgG levels. RESULTS: With a chest x-ray score cut-off of 71, specificity was 88%. With an x-ray score of >71 combined with history of massive haemoptysis, 86% cases were found to be IgG positive. The specificity of this combination was 96%. CONCLUSION: This study concluded that a simple chest x-ray scoring system in addition to the symptom of massive haemoptysis helped in the decision on further evaluation of the subject for CPA, especially in resource constrained settings.

The performance of reverse transcriptase assay for the estimation of the plasma viral load in HIV-1 and HIV-2 infections.

Viral load testing for human immunodeficiency virus 1 (HIV-1) in resource-poor settings continues to be a challenge. Although antiretroviral therapy (ART) is being made available in developing countries, monitoring of viral load is not being done on a regular basis. The purpose of this study was to assess the utility of Cavidi version 3.0, which measures the plasma reverse transcriptase (RT) activity and compare its performance with molecular HIV viral load assays. In all, 125 HIV-1 and 13 HIV-2 positive samples were analyzed. The overall sensitivity of the assay was 86.8% and 94.1% for viral load >1000 copies/ml measured by Qiagen Artus HIV-1 RG RT PCR and Abbott RealTime HIV-1 PCR assays, respectively. Compared with the routine molecular viral load assays, Cavidi version 3.0 is inexpensive, user-friendly, the expenditure on infrastructure is minimal, and it can be used for monitoring of both HIV types.