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.

Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMM and ISHAM in cooperation with the ASM.

Cryptococcosis is a major worldwide disseminated invasive fungal infection. Cryptococcosis, particularly in its most lethal manifestation of cryptococcal meningitis, accounts for substantial mortality and morbidity. The breadth of the clinical cryptococcosis syndromes, the different patient types at-risk and affected, and the vastly disparate resource settings where clinicians practice pose a complex array of challenges. Expert contributors from diverse regions of the world have collated data, reviewed the evidence, and provided insightful guideline recommendations for health practitioners across the globe. This guideline offers updated practical guidance and implementable recommendations on the clinical approaches, screening, diagnosis, management, and follow-up care of a patient with cryptococcosis and serves as a comprehensive synthesis of current evidence on cryptococcosis. This Review seeks to facilitate optimal clinical decision making on cryptococcosis and addresses the myriad of clinical complications by incorporating data from historical and contemporary clinical trials. This guideline is grounded on a set of core management principles, while acknowledging the practical challenges of antifungal access and resource limitations faced by many clinicians and patients. More than 70 societies internationally have endorsed the content, structure, evidence, recommendation, and pragmatic wisdom of this global cryptococcosis guideline to inform clinicians about the past, present, and future of care for a patient with cryptococcosis.

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.

Overcoming clinical challenges in the management of invasive fungal infections in low- and middle-income countries (LMIC).

INTRODUCTION: The management of invasive fungal infections (IFIs) in low- and middle-income countries (LMIC) is a serious challenge due to limited epidemiology studies, sub-optimal laboratory facilities, gap in antifungal management training and resources. Limited studies highlighted distinctive epidemiology of IFIs in those countries, and difficulty in distinguishing from closely related infections. To overcome the gaps for appropriate management of IFIs, innovative approaches are required. AREAS COVERED: Extensive literature search and discussion with experts have helped us to summarize the epidemiology, diagnostic and management difficulties in managing IFIs in LMIC, and recommend certain solutions to overcome the challenges. EXPERT OPINION: The strategies to overcome the challenges in diagnosis may include local epidemiology study, training of healthcare workers, association of fungal infections with already existing budgeted national programs, development and incorporation of point-of-care test (POCT) for prompt diagnosis, simplifying clinical diagnostic criteria suitable for LMIC, judicious use of available expertise, and diagnostic stewardship. For management strategies judicious use of antifungal, partnering with industry for inexpensive antifungal agents, development of LMIC specific guidelines for cost-effective management of IFIs and fungal outbreaks, improvement of infection control practices, advocacy for implementation of WHO recommended antifungal use, and integration of IFIs with public health.

Fever in the returning traveler.

Evaluation of febrile illness in a returning traveler is challenging as it requires careful history taking and knowledge of local epidemiology of endemic and epidemic diseases. Incorporating information of host characteristics for susceptibility of infections is also important for endemic mycosis apart from history of tick bites and animal exposures. Laboratory tests directed by clinical and laboratory parameters will help to reach final diagnosis.

COVID-19 patients' clinical profile and outcome with respect to their vaccination status: A prospective observational multicentre cohort study during third wave in Western India.

PURPOSE: To understand the benefits of COVID-19 vaccination (Covishield, Covaxin) on clinical features and outcome of COVID-19 during the third wave in India. MATERIALS AND METHODS: The primary study aim was to describe the clinical profile and outcome of COVID-19 regarding their vaccination and to identify risk factors for disease progression in vaccinated patients. This was a prospective observational multicentric study of COVID-19 attended by Infectious Disease physicians during January 15, 2022 to February 15, 2022. Adult patients with positive RT-PCR or rapid antigen test for COVID-19 were enrolled. Patient received treatment as per local institutional protocol. Chi square test for categorical and Mann Whitney test for continuous variables were applied for the analysis. Logistic regression was used to calculate adjusted odds ratios. RESULTS: A total of 788 patients were included in analysis out of 883 enrolled patients from 13 centers across Gujarat. By the end of two weeks' follow up, 22 patients (2.8%) had expired. The Median age of subjects was 54 years, with a (55.8%) male. 90% of the subjects were vaccinated, majority (77%) of them had received 2 doses of vaccine with Covishield (659, 93%). Mortality among the non-vaccinated was significantly (11.4%) higher than vaccinated (1.8%). Logistic regression analysis showed numbers of comorbidities (p â€‹= â€‹0.027), baseline higher WBC count (p â€‹= â€‹0.02), higher NLR (p â€‹= â€‹0.016), and Ct value (p â€‹= â€‹0.046) were associated with mortality while vaccination was associated with survival (p â€‹= â€‹0.001). The factors associated with mortality among vaccinated were age, comorbidities, baseline higher WBC, NLR, and CRP. CONCLUSIONS: Omicron variant was associated with mild symptoms. Clinical and laboratory risk factors for getting severe disease with Omicron variant were the same with previous SARS CoV-2 strain. Two doses of vaccine protect people against severe disease and death. Age, comorbidities, baseline leucocytosis, high NLR, elevated CRP are the risk factors for poor outcome in vaccinated patients.

A young female with fever, abdominal pain and eosinophilia.

Fascioliasis has been reported from many countries across the globe. Acute phase of liver fluke is characterised by fever, abdominal pain and peripheral blood eosinophilia while the chronic phase is marked by chronic inflammation involving biliary tract. It is commonly diagnosed by a radiologist due to characteristic branching abscesses seen on CT scan, highly suggestive of liver fluke. Diagnosis is made by demonstration of eggs on direct microscopic examination of duodenal aspirate or bile. Screening of family members is recommended once diagnosis is has been made. Triclabendazole is the drug of choice for treatment.

Risk factors for COVID-19 associated mucormycosis in India: A case control study.

The coronavirus disease 2019 (COVID-19) pandemic had led to an increase in a surge of mucormycosis in COVID-19 patients, especially in India. Diabetes and irrational usage of corticosteroids to treat COVID-19 were some of the factors implicated for COVID-19-associated mucormycosis (CAM). We designed this case-control study to identify risk factors for mucormycosis in COVID-19 patients. The study was conducted at a private tertiary care center in western India. Data were extracted from records of COVID 19 patients (January-May 2021) and divided into two groups: Those with proven or probable mucormycosis, and those without mucormycosis with a ratio of 1:3. A binary logistic regression analysis was done to assess potential risk factors for CAM. A total of 64 CAM and 205 controls were included in the analysis. Age and sex distribution were similar in cases and controls with the majority of males in both the groups (69.9%) and the mean age was 56.4 (±13.5) years. We compared the comorbidities and treatment received during acute COVID-19, specifically the place of admission, pharmacotherapy (steroids, tocilizumab, remdesivir), and the requirement of oxygen as a risk factor for CAM. In a multivariate analysis, risk factors associated with increased odds of CAM were new-onset diabetes (vs. non-diabetics, adjusted odds ratio [OR] 48.66, 95% confidence interval [CI] 14.3-166), pre-existing diabetes (vs. non-diabetics, aOR 2.93, 95%CI 1.4-6.1), corticosteroid therapy (aOR 3.64, 95%CI 1.2-10.9) and home isolation (vs. ward admission, aOR 4.8, 95%CI 2-11.3). Diabetes, especially new-onset, along with corticosteroid usage and home isolation were the predominant risk factors for CAM. LAY SUMMARY: This study revealed new-onset diabetes, pre-existing diabetes, corticosteroid therapy, and home isolation as risk factors for COVID-19-associated mucormycosis. Avoiding the use of corticosteroids in non-severe COVID-19 disease coupled with proper blood sugar monitoring and control will help to reduce the CAM burden.

Virological outcome and frequency of low-level viremia in patients receiving generic dolutegravir-containing regimen at a large tertiary care clinic in Western India.

BACKGROUND: Dolutegravir (DTG) is widely used for the management of naïve and treatment-experienced HIV-infected patients. Low-level viremia (LLV) is common in patients receiving nonnucleoside reverse transcriptase inhibitor- and protease inhibitor-containing regimens. However, the incidence of LLV associated with DTG-containing regimen is not well known. OBJECTIVE: The objective of this study was to assess the virological response associated with DTG-containing regimens and explored frequencies of LLV and risk factors for the same. METHODS: We performed a retrospective cohort study of HIV-infected patients receiving generic DTG-containing regimen from February 2017 to July 2019. All adult patients (≥18 years), who completed at least the first follow-up after initiating treatment, were included in this study. LLV was defined as plasma viral load between 20 and 200 copies/ml. RESULTS: A total of 597 patients started DTG-containing regimen during the study period, of which 522 patients met the inclusion criteria. The study patients were categorized into five groups: naïve (n = 86), first-line failure (n = 32), second-line failure (n = 53), switch (n = 325), and HIV-2 (n = 26). Complete virological suppression at 6, 12, and 18 months was achieved in 78.5%, 81.1%, and 70.9% of the patients, respectively. Furthermore, 17.9%, 12.9%, and 23.3% of the patients had LLV at 6, 12, and 18 months, respectively. Persistent LLV was found in 2.9% of the patients. Overall, DTG was well tolerated and was discontinued in only three patients due to neuropsychiatric side effects. CONCLUSION: DTG is well tolerated and effective in suppressing HIV across all antiretroviral treatment categories. The rate of persistent LLV is low in DTG-containing therapy.

Assessment of self-reported adherence to ART and patient's virological/CD4 response in a tertiary care clinic and government free ART clinic.

INTRODUCTION: Treatment adherence to antiretroviral treatment (ART) is critical in reducing morbidity, mortality, and improving the survival in HIV patients. ART is a life-long commitment, and the variety of factors can influence treatment adherence. We studied the factors affecting treatment adherence in the private sector and public sector outdoor clinic in Ahmedabad, India. The primary objective of this study is to compare the level of adherence and factors that influence adherence to ART in patients attending government run free ART program and private setup. METHODS: We conducted a cross-sectional study of 8 weeks among HIV-infected patients who were receiving ART from private clinic and free ART center from July 2019 to September 2019. We enrolled all consecutive patients >18 years of age attending both clinics. Statistical analysis was carried out using the SPSS software version 25.0. Multiple logistic regression was used to identify the factors that were independently associated with adherence to ART. RESULTS: The study enrolled 306 patients, 151 (49.34%) from the outpatient department of private hospital, and 155 (50.65%) from the free ART center. Patients attending private clinics were more likely to have been diagnosed with HIV since ≥10 years compared to free ART center. Higher opportunistic infection rates were found in free ART center (64.51%). Treatment adherence was significantly lower in the patients attending free ART center (P = 0.004). Patients taking concomitant medications for other comorbid conditions (≥4 pills/day) were more likely to exhibit inadequate adherence ([odds ratio] 1.216, 95% confidence interval 1.0171-1.454). Univariate analysis showed that age, education, habits of alcohol, tobacco, number of pills, and duration of disease played a significant role in predicting adherence to ART (P < 0.05). CONCLUSIONS: Patients attending private clinic are surviving longer with HIV diagnosis, have fewer opportunistic infections, and have better treatment adherence compared to free ART clinic.

The epidemiology of non-Candida yeast isolated from blood: The Asia Surveillance Study.

BACKGROUND: Current guidelines recommend echinocandins as first-line therapy for candidemia. However, several non-Candida yeast are non-susceptible to echinocandins (echinocandin non-susceptible yeast, ENSY), including Cryptococcus, Geotrichum, Malassezia, Pseudozyma, Rhodotorula, Saprochaete, Sporobolomyces and Trichosporon. In laboratories that are not equipped with rapid diagnostic tools, it often takes several days to identify yeast, and this may lead to inappropriate presumptive use of echinocandins in patients with ENSY fungemia. The aim of this study was to determine the distribution of ENSY species during a 1-year, laboratory surveillance programme in Asia. METHODS: Non-duplicate yeast isolated from blood or bone marrow cultures at 25 hospitals in China, Hong Kong, India, Singapore, Taiwan and Thailand were analysed. Isolates were considered to be duplicative if they were obtained within 7 days from the same patient. RESULTS: Of 2155 yeast isolates evaluated, 175 (8.1%) were non-Candida yeast. The majority of non-Candida yeast were ENSY (146/175, 83.4%). These included Cryptococcus (109 isolates), Trichosporon (23), Rhodotorula (10) and Malassezia (4). The proportion of ENSY isolates (146/2155, 6.7%) differed between tropical (India, Thailand and Singapore; 51/593, 8.6%) and non-tropical countries/regions (China, Hong Kong and Taiwan; 95/1562, 6.1%, P = 0.038). ENSY was common in outpatient clinics (25.0%) and emergency departments (17.8%) but rare in intensive care units (4.7%) and in haematology-oncology units (2.9%). Cryptococcus accounted for the majority of the non-Candida species in emergency departments (21/24, 87.5%) and outpatient clinics (4/5, 80.0%). CONCLUSIONS: Isolation of non-Candida yeast from blood cultures was not rare, and the frequency varied among medical units and countries.

Histoplasmosis in non-endemic North-Western part of India.

PURPOSE OF STUDY: The western and North-Western parts of India are usually considered non-endemic for histoplasmosis. On the contrary, we observe histoplasmosis cases with relatively higher frequency from this region although the awareness and laboratory facility to diagnose the disease are not adequate. Hence, we planned the present retrospective study to compile the cases and to analyse different clinical parameters. MATERIALS AND METHODS: Medical records of the patients diagnosed with histoplasmosis during January 2012-August 2017 at two infectious disease clinics of Ahmedabad were included in this study. RESULTS: During the study, 12 cases of histoplasmosis were diagnosed. The median age of the patients was 53 years; all males except one. The diagnosis of histoplasmosis was confirmed on histopathology for 11 cases, and one patient was diagnosed as probable histoplasmosis. The patients were either from Gujarat or Rajasthan without any travel history to endemic zone of histoplasmosis, except one patient. The majority (67%) of the patients had no apparent immunosuppression. Adrenal enlargement, oral ulcers and lymphadenopathy were common presentations in four patients each. We lost two patients in follow-up, and rest 10 patients responded to either to amphotericin B deoxycholate and/or itraconazole therapy. CONCLUSION: This study highlights that Gujarat and Rajasthan are an endemic region for histoplasmosis, and a systematic study is required to understand epidemiology of the disease. Histoplasmosis should be a differential diagnosis in a patient presenting with adrenal enlargement, lymphadenopathy, oral ulcers and fever of unknown origin in this region.

Incidence of symptomatic CSF viral escape in HIV infected patients receiving atazanavir/ritonavir (ATV/r)-containing ART: a tertiary care cohort in western India.

This single-center study attempts to quantify the incidence of symptomatic CSF viral escape (CSFVE) in patients receiving atazanavir/r (ATV/r)-containing regimen. We performed a retrospective analysis of patients receiving ATV/r-containing ART who were diagnosed with symptomatic CSFVE from August 2012 to January 2017. Primary objective was to assess the incidence of symptomatic CSFVE in patients receiving ATV/r-containing ART in clinical practice. Incidence rates were calculated by dividing the number of patients who experienced CSFVE by the number of person-months at risk and summarized as per 10,000 (ten thousand) person-months at risk. Nine hundred thirty-three patients receiving ATV/r containing ART with a total of 36,068 person-months of follow-up were included. Incidence rate of symptomatic CSFVE was 4.4 per 10,000 person-months (95% CI 2.7 to 7.2). The incidence of CSFVE was 9.5 per 10,000 person-months (95% CI 5.7 to 15.7) when the nadir CD4 count was ≤ 200 compared to 0.49 (95% CI 0.07 to 3.5) with a nadir CD4 count > 200 (IRR 19.1 (95% CI 2.93 to 802.8), p < 0.0001). Nadir CD4 count ≤ 200 was associated with substantially increased risk of symptomatic CSFVE, further strengthening efforts to diagnose and treat patients early in disease.

Mucormycosis at a tertiary care centre in Gujarat, India.

The prevalence of mucormycosis is reportedly high in India, although the studies are mainly from north and south India only. We analysed the mucormycosis cases at tertiary care centres of West India. We retrieved the clinical details of all the patients with probable and proven mucormycosis diagnosed at Sterling Hospital and ID clinic at Ahmedabad, Gujarat over the period from 1 January 2013 through 30 April 2015. The data were analysed to determine demography, risk factors, underlying diseases, site of infection and outcome of these patients. A total of 27 patients with the median age of 50 (16-65) years were diagnosed with mucormycosis during the period. Rhino-orbital-cerebral mucormycosis was the most common (51.9%) presentation. Majority (55.6%) of the patients had uncontrolled diabetes with or without ketoacidosis; 25.9% patients had no underlying disease and most of them (85.7%) had cutaneous mucormycosis. In this group, the mortality was 25.9% and an equal percentage of patients were lost to follow up; 14 (51.9%) patients could complete 6 weeks of amphotericin B therapy. All patients who completed antifungal therapy survived except one. Like other parts of India, uncontrolled diabetes was the predominant risk factor for mucormycosis in our group. Patients completing 6 weeks of amphotericin B treatment were likely to survive.

Microsporidial polymyositis in human immunodeficiency virus-infected patients, a rare life-threatening opportunistic infection: clinical suspicion, diagnosis, and management in resource-limited settings.

INTRODUCTION: Microsporidial myositis is a rare opportunistic infection that has been reported in HIV-infected and HIV-uninfected immunocompromised patients. METHODS: In this study we present a retrospective analysis of 5 cases of microsporidial myositis in HIV-infected patients, including the clinical, laboratory, and histologic features, and a review of the literature. RESULTS: Five young men with HIV infection [median CD4 count of 20 cells (range 14-144)/mm(3) ] who presented with signs and symptoms suggestive of myositis underwent EMG-NCV and muscle biopsy, which revealed signs compatible with microsporidial myositis. Early and aggressive treatment led to improvement in 3 patients. Two of the 5 patients died due to a delay in diagnosis, because the spores were mistaken for Candida without confirmatory stains or a high index of suspicion. CONCLUSIONS: Myositis in HIV-infected patients with low CD4 counts should be evaluated using muscle biopsy. A high index of suspicion is required for early diagnosis of microsporidial myositis in HIV-infected patients. Early diagnosis and immediate, aggressive treatment are the keys to favorable outcomes in these patients.

Living related donor renal transplant in human immunodeficiency virus infected patient: case reports from tertiary care hospital in Western India.

Renal transplantation (TX) in human immunodeficiency virus (HIV) infected patients with end stage renal disease (ESRD) is increasingly performed in developed countries in the era of antiretroviral therapy (ART). Management of HIV infected patients during and post-transplant is very complex and challenging due to drug interaction, infection risk and associated co-infections. We described our experience with living related donor renal TX in three HIV infected patients.