Early detection, reactivation of cytomegalovirus DNA & immediate early (IE)-mRNA expression in hematopoietic stem cell-transplant patients.

BACKGROUND: Human cytomegalovirus (HCMV) reactivation is a major cause of morbidity and mortality among stem cell transplant recipients post-transplantation. AIM: HCMV immediate-early messenger RNA (IE-mRNA) was evaluated as marker of post-transplant HCMV reactivation in bone marrow transplant recipients. METHOD: ology: An in-house real-time reverse transcriptase PCR targeting IE-mRNA was developed to estimate HCMV mRNA levels post-transplantation. Blood samples collected in K2-EDTA tubes from patients (n = 162) admitted with Department of Clinical Hematology were transported in cold condition for routine HCMV DNA screening. For HCMV IE-mRNA quantification, peripheral blood mononuclear cells (PBMCs) were separated from whole blood and stored in RNA later at -70 °C until testing. Samples were collected weekly once for first 3 weeks post-transplantation and thereafter from week 4-12, samples were collected twice weekly. A total of 2467 samples were collected from 162 study participants. RESULTS: Thirty five patients (21.6 %) had post-transplant HCMV reactivation. Twenty five patients with complete follow-up were selected for monitoring HCMV DNA. HCMV IE-mRNA PCR was performed for 15 patients and 7(46.6 %) patients had detectable mRNA levels. HCMV IE-mRNA was detected in all patients with increasing HCMV DNA levels except for one patient in whom IE-mRNA appeared 3 days before HCMV DNA was detected. One patient had detectable HCMV IE-mRNA during declining HCMV DNA level. However the patient showed an increased HCMV DNA one week later, indicating the importance of HCMV mRNA in predicting HCMV replication. CONCLUSION: Quantification of HCMV IE-mRNA may be a valuable tool to predict progression of HCMV infection post-transplantation, with further prospective studies needed for validation.

Costs & outcomes of hospitalized scrub typhus infection in a tertiary hospital in south India.

Background & objectives: Scrub typhus is a rickettsial infection seen along the Asian-Pacific rim and imposes a considerable burden on affected people in low- and middle-income countries. The present study was aimed to determine the direct cost of hospitalization of scrub typhus and its trend over six years. Methods: This was a retrospective, observational, hospital based study of individuals admitted to the hospital, diagnosed with scrub typhus over six years, from January 2013 to December 2018. The potential out of pocket expenditure was evaluated. Results: A total of 198 patients were included in the study. The median cost of admission (adjusted to INR 2020) for the six years (2013 to 2018) was found to be ₹ 37,026 (US $ 490) [interquartile range (IQR) 22,996-64,992]. The median cost for patients admitted to the intensive care unit (ICU) was ₹ 128,046 (US $ 1695) (IQR 71,575-201,171), while the cost for patients admitted to the ward-alone was ₹ 33,232 (US $ 440) (IQR 19,609-45,373). The multivariable analysis showed that ARDS and SOFA score were the independent predictors of ICU admission. Interpretation & conclusions: Hospitalisation for scrub typhus is associated with a substantial healthcare expense. The predictors of increased cost were the presence of acute respiratory distress syndrome (ARDS), shock, increasing sequential organ failure assessment (SOFA) score and duration of hospital stay.

The role and diagnostic accuracy of serology for COVID-19.

BACKGROUND: The role and performance of various serological tests for the diagnosis of COVID-19 are unclear. This study aimed to evaluate the performance of seven commercially available serological assays for SARS-CoV-2 antibodies by testing COVID-19 cases and controls. METHODS: Adult patients with fever for > 5 days, admitted to a tertiary-care teaching hospital in South India, were enrolled prospectively between June and December 2020. SARS-CoV-2 RT-PCR confirmed patients were classified as cases, and patients with febrile illness with laboratory-confirmed alternative diagnosis and healthy participants were controls. All participants were tested with SCoV-2 Detect™ IgM ELISA kit and SCoV-2 Detect™ IgG ELISA kit (InBios International, Seattle, USA) (Inbios), SARS-CoV-2 Total and SARS-CoV-2 IgG (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) (Siemens), Roche Elecsys® Anti-SARS-CoV-2 (Roche Diagnostics, Rotkreuz, Switzerland) (Roche), Abbott SARS-CoV-2 IgG (Abbott Diagnostics, IL, USA) (Abbott), and Liaison® SARS-CoV-2 S1/S2 IgG (DiaSorinS.p.A., Saluggia, Italy) (Liaison). The sensitivities, specificities, positive predictive values (PPV), negative predictive values (NPV), and accuracies were compared. RESULTS: There were 303 participants: 153 cases and 150 controls. ELISA detecting anti-S protein antibody was more sensitive (88.9% for IgG and 86.3% for IgM) than the CLIAs (82.4% for total antibodies and 76.5-85.6% for IgG). Among CLIAs, Roche IgG was most sensitive (85.6%) followed by Abbott (83%) and Liaison (83%). Abbot had the best PPV (88.8%) and was more specific (89.3%) than Liaison (82%) and Roche (82%). Siemens IgG was less sensitive (76.5%) than Siemens Total (82.4%). The specificity of all the serological assays was modest (75-90%). Antibody test positivity increased with the duration of illness reaching 90% after 10 days of illness. When cases were compared against pre-pandemic controls, the IgG gave excellent specificity (98-100%). For seroprevalence studies, InBios IgG had the best accuracy (90.8%) with 88.9% sensitivity and 97.6% specificity. CONCLUSION: The serological assays are important adjuncts for the diagnosis of COVID-19 in patients with persistent symptoms, especially in the second week of illness. The value of serological diagnostic tests is limited in the first week of illness and they provide additional value in seroprevalence studies. The diagnostic accuracy of the ELISA and CLIA platforms were comparable.

Community-acquired fungal pyelonephritis with renal infarction and gangrene of the colon: an uncommon diagnosis.

A 54-year-old male farmer with a history of long-standing uncontrolled type 2 diabetes mellitus (HbA1c 10.8) presented with a 3-week history of fever, intermittent vomiting, malaise and left flank pain for which he was treated with broad-spectrum antibiotics and oral antifungals for Candida isolated from urine culture. CT of the abdomen revealed predominant involvement of the left kidney and retroperitoneal structures. Nephrectomy was performed due to worsening abdominal pain and features of bowel perforation found on imaging. Pus culture from the necrotic kidney grew aseptate fungal hyphae, and the histopathological examination was suggestive of zygomycosis. He received amphotericin B postoperatively, but his condition deteriorated and he succumbed to nosocomial gram-negative septicaemia.

Critical Care for COVID-19 Affected Patients: Updated Position Statement of the Indian Society of Critical Care Medicine.

The management of coronavirus disease-2019 (COVID-19) is witnessing a change as we learn more about the pathophysiology and the severity of the disease. Several randomized controlled trials (RCTs) and meta-analysis have been published over the last few months. Several interventions and therapies which showed promise in the initial days of the pandemic have subsequently failed to show benefit in well-designed trials. Understanding of the methods of oxygen delivery and ventilation have also evolved over the past few months. The Indian Society of Critical Care Medicine (ISCCM) has reviewed the evidence that has emerged since the publication of its position statement in May and has put together an addendum of updated evidence. How to cite this article: Mehta Y, Chaudhry D, Abraham OC, Chacko J, Divatia J, Jagiasi B, et al. Critical Care for COVID-19 Affected Patients: Position Statement of the Indian Society of Critical Care Medicine. Indian J Crit Care Med 2020;24(Suppl 5):S225-S230.

Performance of molecular and serologic tests for the diagnosis of scrub typhus.

Diagnosis of scrub typhus, caused by the bacterium Orientia tsutsugamushi, is challenging because of the overlap of its non-specific symptoms with other infections coupled with the lack of sufficient data on the performance of diagnostic tests. Early diagnosis of scrub typhus is crucial to improve outcomes and this study evaluates the diagnostic performance of various tests. The present study aims at assessing the accuracy of various rapid diagnostic tests, serologic tests, and nucleic acid amplification methods on well-characterized patient samples. Adult patients with acute febrile illness and manifestations suggestive of scrub typhus confirmed by positive PCR in the blood, eschar or tissue were characterized as cases. Patients with acute febrile illness and a confirmed alternate etiology such as culture-confirmed typhoid, smear/PCR positive for malaria, PCR/NS1 antigen positive for dengue, PCR positive for influenza, PCR/MAT positive for leptospirosis, PCR positive for spotted fever were characterized as controls with other infections. The healthy controls consisted of subjects from the same geographic region. We performed the following tests on blood samples for scrub typhus and calculated the sensitivity, specificity, positive predictive value, and negative predictive value: (1) Quantitative real time PCR using 47kDa gene (qPCR); (2) Conventional PCR using 56kDa gene (cPCR); (3) Loop-mediated isothermal amplification assay (LAMP assay); (4) Immunofluorescence assay (IFA); (5) Enzyme-linked immunosorbent assay (ELISA); (6) Weil-Felix test(WF test); and (7) Immunochromatographic Rapid Diagnostic Test (RDT).Among the 316 participants, 158 had confirmed scrub typhus (cases) and 158 were controls. ELISA and RDT detecting Orientia tsutsugamushi specific IgM antibodies had excellent discriminative potential with sensitivities and specificities of 92%, 94% and 92%, 92% respectively. The sensitivity and specificity of IFA were found to be 95% and 74% respectively. IgM serology had a false positivity rate of 8% with other acute febrile illnesses such as dengue, leptospirosis and spotted fever due to the nonspecific binding of the pentavalent IgM. LAMP assay had 91.7% sensitivity and 77.2% specificity while qPCR provided excellent sensitivity (97%) and perfect specificity. In conclusion, ELISA and RDT detecting Orientia tsutsugamushi specific IgM antibodies have excellent sensitivity and specificity while the accuracy of IFA is suboptimal for the diagnosis of scrub typhus. Given its perfect specificity and superior sensitivity, qPCR is preferred for diagnostic confirmation in reference laboratories particularly for diagnosis of early disease with less than 7 days duration. This study provides a comprehensive evaluation of all currently available diagnostic tests for scrub typhus.

Acute infectious purpura fulminans: a case series from India.

Acute infectious purpura fulminans is a serious, potentially fatal condition. We present a case series of 11 patients from March 2005 to March 2017, whose clinical symptoms were fever (100%), confusion (63.6%) and headache (55%), and whose common laboratory abnormalities were thrombocytopenia (100%), elevated alkaline phosphatase (70%) and anaemia (63.6%). Three patients (27%) developed gangrene and two presented in shock. Only one grew Neisseria meningitidis in cerebrospinal fluid (CSF) culture and another confirmed by latex agglutination and polymerase chain reaction in CSF. Five others had serology confirmed spotted fever rickettsioses (SFG). All received broad spectrum antibiotics; in 9/11 patients, this included doxycycline or azithromycin. The mean hospital stay was 10.2 days and overall mortality was 18.2%.

Clinical management of COVID-19.

The novel coronavirus disease 2019 (COVID-19) with its early origin from Wuhan city in China has evolved into a global pandemic. Maximal precautionary measures and resources have been put forward by most nations in war footing to mitigate transmission and decrease fatality rates. This article was aimed to review the evidence on clinical management and to deal with the identification of high-risk groups, warning signs, appropriate investigations, proper sample collection for confirmation, general and specific treatment measures, strategies as well as infection control in the healthcare settings. Advanced age, cardiovascular disease, diabetes, hypertension and cancer have been found to be the risk factors for severe disease. Fever lasting for >five days with tachypnoea, tachycardia or hypotension are indications for urgent attention and hospitalization in a patient with suspected COVID-19. At present, reverse transcription-polymerase chain reaction (RT-PCR) from the upper respiratory tract samples is the diagnostic test of choice. While many drugs have shown in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are insufficient clinical data to promote or dissuade their usage. Among the currently available drugs, hydroxychloroquine and lopinavir/ritonavir may be considered for patients with severe COVID-19 infection, awaiting further clinical trials. Stringent droplet and contact precautions will protect healthcare workers against most clinical exposures to COVID-19.

Critical Care for COVID-19 Affected Patients: Position Statement of the Indian Society of Critical Care Medicine.

The global pandemic involving severe acute respiratory syndrome-coronavirus-2 (SARS-COV-2) has stretched the limits of science. Ever since it emerged from the Wuhan province in China, it has spread across the world and has been fatal to about 4% of the victims. This position statement of the Indian Society of Critical Care Medicine represents the collective opinion of the experts chosen by the society. HOW TO CITE THIS ARTICLE: Mehta Y, Chaudhry D, Abraham OC, Chacko J, Divatia J, Jagiasi B, et al. Critical Care for COVID-19 Affected Patients: Position Statement of the Indian Society of Critical Care Medicine. Indian J Crit Care Med 2020;24(4):222-241.

Trainee doctors in medicine prefer case-based learning compared to didactic teaching.

BACKGROUND: Sustaining interest and promoting deep learning is a challenge in any teaching method. The purpose of the study is to find the perception of trainee doctors in Internal Medicine and teaching faculty on the usefulness of case-based learning (CBL) and to compare assessment knowledge outcome with didactic seminars. METHODS AND MATERIALS: We developed and conducted a CBL teaching program on eight topics in infectious diseases. First group had CBL and second group had didactic seminars. In step 1, a clinical case was introduced in stages. Learning objectives were formulated and topics were divided among the trainees. At step 2, trainees shared what they had learnt from self-directed learning. Faculty summarized the case and learning points. In the seminar group, trainees made presentations on the given topics. Trainees who had CBL underwent a questionnaire survey. Multiple choice questions-based test was administered for both the groups. RESULTS: The trainee doctors and staff overwhelmingly found CBL to be more interesting, stimulating, and useful compared to didactic seminars. There was no statistical difference in the test scores. CONCLUSIONS: CBL is a useful and interesting method of learning and should be employed more often in teaching for trainee doctors.

Acute oleander poisoning: A study of clinical profile from a tertiary care center in South India.

INTRODUCTION: Yellow oleander (Thevetia peruviana), which belongs to the Apocyanaceae family, is a common shrub seen throughout the tropics. All parts of the plant contain high concentrations of cardiac glycosides which are toxic to cardiac muscle and the autonomic nervous system. Here, we describe the clinical profile of patients with oleander poisoning and their outcomes. METHODS AND MATERIALS: This retrospective study was conducted over a period of 12 months (March 2016 to February 2017). The data was extracted from the inpatient electronic medical records. Adult patients with a diagnosis of acute yellow oleander poisoning were included in the study. Descriptive statistics were obtained for all variables in the study and appropriate statistical tests were employed to ascertain their significance. RESULTS: The study comprised 30 patients aged 30.77 ± 12.31 (mean ± SD) who presented at 12.29 ± 8.48 hours after consumption of yellow oleander. Vomiting (80%) was the most common presenting symptom. Metabolic abnormalities at presentation included hyperchloremia in 22 patients and metabolic acidosis (bicarbonate <24 mmol/L) in 29 patients. Fifteen (50%) patients had abnormal ECG, of which second-degree AV block was the commonest ECG abnormality seen in 4 (13.3%). Fifteen (50%) patients had transvenous temporary pacemaker insertion (TPI). Having a TPI significantly prolonged the duration of hospital stay (OR 1.85, 95% CI 1.06-3.21, P 0.03). The mortality in the cohort was 2 (6.7%). CONCLUSION: In patients with yellow oleander poisoning, dyselectrolytemia with ECG abnormalities was common. TPI prolonged the duration of hospital stay. Further studies are required to know the indication for and to ascertain the effect of temporary pacing on survival.

Symptomatic HIV CNS viral escape among patients on effective cART.

OBJECTIVE: The clinical syndrome in symptomatic HIV associated CNS viral escape is poorly defined. We attempted to describe the clinical syndrome, laboratory profile, radiological features and outcomes of HIV infected patients with symptomatic central nervous system (CNS) viral escape in our study. METHODS: This is a retrospective study were adult patients with HIV infection on cART admitted with a diagnosis of CD8 encephalitis or CNS viral escape in a large teaching hospital in South India was identified. RESULTS: The mean age of the eleven patients included in the study was 37.5 years. Most patients had received almost a decade of antiretroviral treatment at diagnosis (mean: 11.18 years). All patients presented with global cerebral syndrome. Cognitive decline, tremors, and headaches were common manifestations. All patients had lymphocytic pleocytosis (mean cell count: 44.63 cells/ml; lymphocyte percentage: 94.81%) with elevated protein (mean: 125.36 mg/dl). All patients were on boosted protease inhibitors (81.8% on Atazanavir and 18.18% Lopinavir). All except one patient was on Tenofovir and lamivudine combination therapy. White matter changes and deep brain nuclei involvement were common. Most patients required a change of cART to regimens with better CNS penetration and suppression of the resistant virus in the plasma and improved. CONCLUSION: CNS viral escape should be considered as a differential among patients on Atazanavir presenting with non-focal cerebral syndrome and CSF lymphocytic pleocytosis.

Direct cost of illness for dengue in hospitalized children and adults at a referral hospital in India.

OBJECTIVES: To describe the direct cost of illness in pediatric and adult inpatients at a referral hospital in India. METHODS: Inpatients who tested positive for dengue were identified in the hospital records of a single private non-profit hospital over a period of 1 year and line-listed. Hospital discharge bills were obtained for pediatric and adult patients and the median costs by severity of illness for bed and treatment were estimated. Costs were also converted to US dollars (1 USD=64.6 Indian rupees (INR)). RESULTS: The median and interquartile range (IQR) direct costs for pediatric dengue without warning signs, dengue with warning signs, and severe dengue were 179.80 (IQR 85.51-428.51) USD, 145.06 (IQR 90.89-321.86) USD, and 933.51 (IQR 400.50-1117.43) USD, respectively. The median and IQR direct costs for adult dengue without warning signs, dengue with warning signs, and severe dengue were 312.75 (IQR 174.55-531.03) USD, 287.22 (IQR 210.96-389.34) USD, and 720.39 (IQR 389.23-1035.51) USD, respectively. CONCLUSIONS: Children and adults with dengue incur high costs when hospitalized for dengue. Since most medical costs in India are out-of-pocket expenses, these illnesses can impact households.

Newer ß-Lactam/ß-Lactamase inhibitor for multidrug-resistant gram-negative infections: Challenges, implications and surveillance strategy for India.

Antimicrobial resistance (AMR) is a major public health concern across the globe, and it is increasing at an alarming rate. Multiple classes of antimicrobials have been used for the treatment of infectious diseases. Rise in the AMR limits its use and hence the prerequisite for the newer agents to combat drug resistance. Among the infections caused by Gram-negative organisms, beta-lactams are one of the most commonly used agents. However, the presence of diverse beta-lactamases hinders its use for therapy. To overcome these enzymes, beta-lactamase inhibitors are being discovered. The aim of this document is to address the burden of AMR in India and interventions to fight against this battle. This document addresses and summarises the following: The current scenario of AMR in India (antimicrobial susceptibility, resistance mechanisms and molecular epidemiology of common pathogens); contentious issues in the use of beta-lactam/beta-lactamase inhibitor as an carbapenem sparing agent; role of newer beta-lactam/beta-lactamase inhibitor agents with its appropriateness to Indian scenario and; the Indian Council of Medical Research interventions to combat drug resistance in terms of surveillance and infection control as a national response to AMR. This document evidences the need for improved national surveillance system and country-specific newer agents to fight against the AMR.

Invasive fungal infection following chemotherapy for acute myeloid leukaemia-Experience from a developing country.

The incidence of invasive fungal infections (IFI) is believed to be higher in patients with acute myeloid leukaemia (AML) undergoing chemotherapy in non-HEPA-filtered rooms. The aim of this study is to review the incidence of IFI in a large cohort of patients with AML treated at a single centre in India. Two hundred and twenty-two patients with AML treated with either induction chemotherapy or salvage chemotherapy between 2008 and 2013 were studied retrospectively. IFI was defined as per the revised EORTC-MSG criteria. Data on type of chemotherapy, prophylactic strategies, engraftment (ANC>500), the presence of IFI and survival were collected. IFI was diagnosed in 86 patients (38.7%) with proven IFI in 12 (5.4%). Use of posaconazole prophylaxis (P=.001) was the only factor associated with reduced incidence of IFI. Survival in patients with proven IFI was lower than those without proven IFI, but not statistically significant (59.4% vs 78.5%; P=.139). There is a high incidence of IFI during induction chemotherapy for acute myeloid leukaemia in developing countries. Posaconazole prophylaxis was associated with a significantly lower incidence of IFI. Optimal yet cost-effective strategies for prevention and early diagnosis of IFI are required to improve survival in patients undergoing chemotherapy for AML.

Effect of Interleukin-28B polymorphism on Interleukin-28 expression and immunological recovery amongst HIV-1-infected individuals following antiretroviral therapy.

PURPOSE: Type III interferon is well known to have diverse antiviral and immunomodulatory activities. Studies describing the association of interleukin (IL)-28 polymorphisms in treatment-experienced HIV participants are limited. This study was aimed to determine the association of IL-28B gene polymorphisms with immunological recovery in HIV patients on 6-9 months of antiretroviral therapy (ART). METHODS: Eighty treatment-naive HIV patients were recruited, of which 48 patients were followed up after 6-9 months of ART. Whole blood samples were collected before and after 6-9 months of ART. CD4, CD8 and CD3 counts were enumerated flow cytometry. IL-28B polymorphisms (rs12979860 and rs8099917) were profiled by polymerase chain reaction (PCR)-restriction fragment length polymorphism. The IL-28 mRNA and plasma HIV-1 viral load were estimated using real-time PCR and plasma IL-28 level by ELISA. RESULTS: The CD4, CD4/CD3%, IL-28 mRNA and reversal of CD4/CD8 ratio were significantly increased following 6-9 months of ART (P < 0.01). The rs12979860 CC genotype and rs12979860:rs8099917 (CC: TT) haplotype showed significant association with higher CD4+ T-cell count amongst treatment-naive HIV-infected individuals (P < 0.05). In addition, there was a significant association of rs12979860 CC genotype with increase in CD4/CD3% following 6-9 months of ART. IL-28 mRNA showed correlation with the HIV-1 viral load, and there was a significant increase in the IL-28 mRNA expression following 6-9 months of ART. CONCLUSION: Our preliminary findings suggest that IL-28 polymorphisms could influence both immunological recovery and therapeutic response in HIV infection. Hence, functional studies are warranted to understand the mechanistic basis of IL-28-mediated host genetic influence on HIV therapeutic response.