Vitamin D enhances host protective immune responses to Mycobacterium tuberculosis by suppressing Interferon-gamma (IFN-g) and reducing disease associated inflammation in the host. The objectives of this study were to determine whether vitamin D supplementation to patients with tuberculosis (TB) could influence recovery.

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.

We report 13 cases of Naegleria fowleri primary amebic meningoencephalitis in persons in Karachi, Pakistan, who had no history of aquatic activities. Infection likely occurred through ablution with tap water. An increase in primary amebic meningoencephalitis cases may be attributed to rising temperatures, reduced levels of chlorine in potable water, or deteriorating water distribution systems.

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.

COVID-19 resulted in extensive morbidity and mortality worldwide. SARS-CoV-2 evolved rapidly, with increasing transmission due to Variants of Concern (VOC). Identifying VOC became important but genome submissions from low-middle income countries (LMIC) remained low leading to gaps in genomic epidemiology. We demonstrate the use of a specific mutation RT-PCR based approach to identify VOC in SARS-CoV-2 positive samples through the pandemic in Pakistan. We selected 2150 SARS-CoV-2 PCR positive respiratory specimens tested between April 2021 and February 2022, at the Aga Khan University Hospital Clinical Laboratories, Karachi, Pakistan. Commercially available RT-PCR assays were used as required for mutations in Spike protein (N501Y, A570D, E484K, K417N, L452R, P681R and deletion69_70) to identify Alpha, Beta, Gamma, Delta, and Omicron variants respectively. Three pandemic waves associated with Alpha, Delta and Omicron occurred during the study period. Of the samples screened, VOC were identified in 81.7% of cases comprising mainly; Delta (37.2%), Alpha (29.8%) and Omicron (17.1%) variants. During 2021, Alpha variants were predominant in April and May; Beta and Gamma variants emerged in May and peaked in June; the Delta variant peaked in July and remained predominant until November. Omicron (BA.1) emerged in December 2021 and remained predominant until February 2022. The CT values of Alpha, Beta, Gamma and Delta were all significantly higher than that of Omicron variants (p<0.0001). We observed VOC through the pandemic waves using spike mutation specific RT-PCR assays. We show the spike mutation specific RT-PCR assay is a rapid, low-cost and adaptable for the identification of VOC as an adjunct approach to NGS to effectively inform the public health response. Further, by associating the VOC with CT values of its diagnostic PCR we gain information regarding the viral load of samples and therefore the level of transmission and disease severity in the population.

Ventriculostomy-associated infection (VAI) is a major concern to physicians. Limited studies have looked at the outcomes of external ventricular drain (EVD) infection and predictors of unfavorable outcomes. In this study, we assessed the outcomes of EVD infection and predictors of unfavorable outcomes. This was a retrospective medical chart review, conducted at the Aga Khan University Hospital. All the patients irrespective of age and gender, fulfilling the diagnostic criteria of VAI were included. Patients with preexisting bacterial meningitis or ventriculitis were excluded from the study. Outcome assessment was based on Glasgow outcome scale (GOS) at 1 and 3 months after procedure. Other outcomes included 30-day mortality and total length of hospital stay. We included 256 patients in the study. 66 patients (25.8%) developed VAI. EVD was the primary procedure in 21 (31.8%) cases. Most patients, 24 (36.4%), had EVD as a secondary procedure for tumor surgery. Median interval between EVD placement and diagnosis of infection was 3 days. Mean length of stay in VAI patients was 31.85 ± 20.53 days. Seven patients required ICU care. Ten patients (15.2%) expired during hospital stay or within 30 days of discharge and further four had GOS of 2 or 3. A total of 52 patients had a favorable outcome after 6 months. Rate of VAI in this cohort was high. VAI is associated with increased morbidity, mortality, and prolonged hospital stay.