Candida auris, a multidrug-resistant yeast that causes invasive infections, was first described in 2009 in Japan and has since been reported from several countries. To understand the global emergence and epidemiology of C. auris, we obtained isolates from 54 patients with C. auris infection from Pakistan, India, South Africa, and Venezuela during 2012–2015 and the type specimen from Japan. Patient information was available for 41 of the isolates. We conducted antifungal susceptibility testing and whole-genome sequencing (WGS). Available clinical information revealed that 41% of patients had diabetes mellitus, 51% had undergone recent surgery, 73% had a central venous catheter, and 41% were receiving systemic antifungal therapy when C. auris was isolated. The median time from admission to infection was 19 days (interquartile range, 9–36 days), 61% of patients had bloodstream infection, and 59% died. Using stringent break points, 93% of isolates were resistant to fluconazole, 35% to amphotericin B, and 7% to echinocandins; 41% were resistant to 2 antifungal classes and 4% were resistant to 3 classes. WGS demonstrated that isolates were grouped into unique clades by geographic region. Clades were separated by thousands of single-nucleotide polymorphisms, but within each clade isolates were clonal. Different mutations in ERG11 were associated with azole resistance in each geographic clade. C. auris is an emerging healthcare-associated pathogen associated with high mortality. Treatment options are limited, due to antifungal resistance. WGS analysis suggests nearly simultaneous, and recent, independent emergence of different clonal populations on 3 continents. Risk factors and transmission mechanisms need to be elucidated to guide control measures.

Summary: Background: Invasive aspergillosis is a well‐known complication of severe influenza pneumonia with acute respiratory distress syndrome (ARDS). However, recent studies are reporting emergence of aspergillosis in severe COVID‐19 pneumonia, named as COVID‐19‐associated pulmonary aspergillosis (CAPA).Methods: A retrospective observational study was conducted in patients with severe COVID‐19 pneumonia from February 2020 to April 2020. Patients ≥18 years of age with clinical features and abnormal chest imaging with confirmed COVID‐19 by RT‐PCR for SARS‐CoV‐2 were included. CAPA was diagnosed based on clinical parameters, radiological findings and mycological data. Data were recorded on a structured proforma, and descriptive analysis was performed using Stata ver 12.1.Results: A total of 147 patients with confirmed COVID‐19 and 23 (15.6%) patients requiring ICU admission were identified. Aspergillus species were isolated from tracheal aspirates of nine (39.1%) patients, and of these, five patients (21.7%) were diagnosed with CAPA and four (17.4%) had Aspergillus colonisation. The mean age of patients with CAPA was 69 years (Median age: 71, IQR: 24, Range: 51‐85), and 3/5 patients were male. The most frequent co‐morbid was diabetes mellitus (4/5). The overall fatality rate of COVID‐19 patients with aspergillosis was 44% (4/9). The cause of death was ARDS in all three patients with CAPA, and the median length of stay was 16 days (IQR: 10; Range 6‐35 days).Conclusion: This study highlights the need for comparative studies to establish whether there is an association of aspergillosis and COVID‐19 and the need for screening for fungal infections in severe COVID‐19 patients with certain risk factors.

Chronic pulmonary aspergillosis (CPA) is a recognized complication of pulmonary tuberculosis (TB). In 2015, the World Health Organization reported 2.2 million new cases of nonbacteriologically confirmed pulmonary TB; some of these patients probably had undiagnosed CPA. In October 2016, the Global Action Fund for Fungal Infections convened an international expert panel to develop a case definition of CPA for resource-constrained settings. This panel defined CPA as illness for >3 months and all of the following: 1) weight loss, persistent cough, and/or hemoptysis; 2) chest images showing progressive cavitary infiltrates and/or a fungal ball and/or pericavitary fibrosis or infiltrates or pleural thickening; and 3) a positive Aspergillus IgG assay result or other evidence of Aspergillus infection. The proposed definition will facilitate advancements in research, practice, and policy in lower- and middle-income countries as well as in resource-constrained settings.

Non-tuberculous mycobacteria (NTM) are ubiquitous dwellers of environmental niches and are an established cause of natural and nosocomial infections. The incidence of NTM infections is rising owing to a growing population of immunocompromised and vulnerable individuals, complex medical and surgical procedures, as well as increased awareness and diagnostic capabilities. The prevalence of different NTM varies between continents, regions, and countries. The true global burden of pulmonary and extrapulmonary disease is unknown and estimates are subject to under and/or over-estimation. Diagnosis requires confirmation by isolation of NTM along with clinical and radiological criteria, which may be suboptimal at all levels. Susceptibility testing is complex and clinical breakpoints are not available for many of the drugs. Frequently, NTM infections are not considered until late in the course of disease. Improved and rapid detection of tuberculosis cases in high-burden countries has, however, also brought NTM infections into the limelight, and has identified a need for research efforts towards rapid diagnostic tests and the identification of biomarkers to monitor the treatment response in patients with NTM infections.

An outbreak of Candida auris began globally in 2014 including Pakistan and since then it has emerged as a nosocomial multi-drug resistant pathogen. The aim of this study was to assess the clinical spectrum and outcome of patients, from a single center in Pakistan, in whom C. auris was isolated. A retrospective study was conducted on 92 patients; ≥16 years with at least one culture positive for C. auris, at the Aga Khan University Hospital Karachi, Pakistan from Sept 2014-Mar 2017.Demographics, clinical history, management and outcome were studied. A logistic regression model was used to identify the risk factors for mortality. We identified 92 patients with C. auris (193 isolates), of whom 52.2% were males. Mean age was 54.14 ± 20.4 years. Positive cultures were obtained after a median hospital stay of 14 days. Most patients had a history of surgery (57.6%), antibiotic use (95.6%), ICU stay (44.6%), indwelling lines (88.04%) and isolation of another multi-resistant organism (52.2%).Most patients were symptomatic (70.7%). Amongst these, 38 had candidemia while 27 had non-candidemia infections. Sites of infection included central lines (35), urinary tract (19), peritonitis (4), nosocomial ventriculitis (1), empyema (1), fungal keratitis (1) otitis externa (1) and surgical site (1). Fluconazole resistance was 100% while 28.5 and 7.9% were Voriconazole and Amphotericin resistant respectively. Overall crude mortality was 42.4% while 14-day mortality was 31.5%. Both infected and colonized cases shared similar mortality (46.2% vs 33.3%; p-value = 0.25). Among infected cases mortality was high in candidemia compared to non-candidemia (60.5% vs 25.9%) in which deaths related to C. auris were 34.2% vs 22.2% respectively. On multivariate analysis candidemia (AOR 4.2, 95% CI: 1.09–16.49; p-value = 0.037) was associated with greater mortality with source control being the only protective factor for mortality (AOR 0.22, 95% CI: 0.05–0.92; p-value0.038] while ICU stay, rapidity of blood culture clearance, DM, malignancy and MDR co-infection had no impact. Patients with C.auris from a single center in Pakistan have a wide clinical spectrum with line associated infection being the predominant site of infection. Candidemia leads to high mortality while source control improves outcome.

Background: Seroconversion rates reported after Hepatitis B virus (HBV) vaccination globally ranges from 85–90%. Health care workers (HCWs) are at high risk of acquiring HBV and non responders' rates after HBV vaccination were not reported previously in Pakistani HCWs. Therefore we evaluated immune response to HBV vaccine in HCWs at a tertiary care hospital in Karachi, Pakistan. Methods: Descriptive observational study conducted at Aga Khan University from April 2003 to July 2004. Newly HBV vaccinated HCWs were evaluated for immune response by measuring serum Hepatitis B surface antibody (HBsAb) levels, 6 weeks post vaccination. Results: Initially 666 employees were included in the study. 14 participants were excluded due to incomplete records. 271 (41%) participants were females and 381(59%) were males. Majority of the participants were young (<25–39 years old), regardless of gender. Out of 652 HCWs, 90 (14%) remained seronegative after six weeks of post vaccination. The percentage of non responders increased gradually from 9% in participants of 50 years of age. Male non responders were more frequent (18%) than female (8%). Conclusion: Seroconversion rate after HBV vaccination in Pakistani HCWs was similar to that reported in western and neighboring population. HCWs with reduced immune response to HBV vaccine in a high disease prevalent population are at great risk. Therefore, it is crucial to check post vaccination HBsAb in all HCWs. This strategy will ensure safety at work by reducing nosocomial transmission and will have a cost effective impact at an individual as well as at national level, which is very much desired in a resource limited country.