Candidaemia and Central Line-Associated Candidaemia in a Network of Indian ICUs: Impact of COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES: Candidaemia is a potentially life-threatening emergency in the intensive care units (ICUs). Surveillance using common protocols in a large network of hospitals would give meaningful estimates of the burden of candidaemia and central line associated candidaemia in low resource settings. We undertook this study to understand the burden and epidemiology of candidaemia in multiple ICUs of India, leveraging the previously established healthcare-associated infections (HAI) surveillance network. Our aim was also to assess the impact that the pandemic of COVID-19 had on the rates and associated mortality of candidaemia. METHODS: This study included adult patients from 67 Indian ICUs in the AIIMS-HAI surveillance network that conducted BSI surveillance in COVID-19 and non-COVID-19 ICUs during and before the COVID-19 pandemic periods. Hospitals identified healthcare-associated candidaemia and central line associated candidaemia and reported clinical and microbiological data to the network as per established and previously published protocols. RESULTS: A total of 401,601 patient days and 126,051 central line days were reported during the study period. A total of 377 events of candidaemia were recorded. The overall rate of candidaemia in our network was 0.93/1000 patient days. The rate of candidaemia in COVID-19 ICUs (2.52/1000 patient days) was significantly higher than in non-COVID-19 ICUs (1.05/patient days) during the pandemic period. The rate of central line associated candidaemia in COVID-19 ICUs (4.53/1000 central line days) was also significantly higher than in non-COVID-19 ICUs (1.73/1000 central line days) during the pandemic period. Mortality in COVID-19 ICUs associated with candidaemia (61%) was higher than that in non-COVID-19 ICUs (41%). A total of 435 Candida spp. were isolated. C. tropicalis (26.7%) was the most common species. C. auris accounted for 17.5% of all isolates and had a high mortality. CONCLUSION: Patients in ICUs with COVID-19 infections have a much higher risk of candidaemia, CLAC and its associated mortality. Network level data helps in understanding the true burden of candidaemia and will help in framing infection control policies for the country.

Seroprevalence of Rickettsial disease: A population-based survey from kashmir valley, North India.

Background: Limited studies have been done regarding the prevalence of Rickettsial diseases in India and as far as UT of Jammu and Kashmir is concerned, only a few hospital-based studies are available. Objectives: The present study was therefore planned to find the seroprevalence of Rickettsial diseases in Kashmir Valley. Materials and Methods: A multistage sampling procedure was used for the collection of samples from 10 districts of Kashmir Valley and a total of 1740 samples were collected. In addition, 802 healthy blood donors were included to establish baseline titers for Weil-Felix (WF) Test. Results: Of 1734 subjects, 73 were positive by the WF test. The overall seroprevalence of Rickettsial diseases was 4.1% with the highest prevalence of scrub typhus (2.30%) followed by the spotted fever group (1.5%) and typhus group (0.40%). Maximum seropositive subjects were from district Kulgam (6.97%) followed by Pulwama (5.92%), Shopian (5.79%), Anantnag (5.47%), Ganderbal (5.00%), Kupwara (4.72%), Baramulla (4.62%), Srinagar (2.63%), Bandipora (2.41%), and Budgam (0.54%), respectively. Seropositivity was higher in females and subjects who had contact with ticks and mites like those involved in the collection of firewood and grass or had contact with uncut grass or shrub. The seropositivity was also significantly higher in those working in paddy fields and those living near the forest (P < 0.05). Conclusion: The results of the present study confirm the existence of Rickettsial diseases in this region. This data would promote awareness of rickettsioses among local physicians and will also serve as a baseline to detect changing prevalence in the future.

Airway Microbiology in Children with Cystic Fibrosis: A Prospective Cohort Study from Northern India.

OBJECTIVE: The objective of this study is to find the organism profile and antimicrobial susceptibility patterns in children with cystic fibrosis (CF). DESIGN: Prospective cohort study. SETTING: Hospital-based study. INTERVENTION: Sputum cultures/throat swabs were collected from the study population. Relevant details like anthropometry, systemic examination findings and investigations were entered in a pre-designed format. Sputum culture was subjected to microbiological analysis at the hospital microbiology laboratory. MAIN OUTCOME MEASURE: Prevalence of positive sputum/cough swab culture in CF patients, their organism profile and antibiotic sensitivity. RESULTS: A total of 63 patients were enrolled in the study. A total of 136 organisms were grown in our study population. Thirteen different organisms were isolated, which included five gram-positive bacteria, six gram-negative bacteria, eight Candida spp. and one filamentous. Antibiotic sensitivity profile of the Pseudomonas aeruginosa showed excellent sensitivity to all the aminoglycosides, piperacillin-tazobacteum and polymixin, similarly methicillin-sensitive Staphylococcus aureus, methicillin-resistant S. aureus and Enterococcus spp. were uniformly sensitive to vancomycin, linezolid and teicoplanin. Fungal isolates showed 100% sensitivity to all the antifungals tested including azoles and amphotericin B. CONCLUSION: We observed 61% of culture positivity for different organisms in our study. Staphylococcus aureus and P. aeruginosa were the most frequently isolated organisms. Pseudomonas aeruginosa isolates were largely sensitive to aminoglycosides, carbapenems and polymixin. We found an unusually higher incidence of enterococcal infection in our study cohort with few vancomycin-resistant isolates.

Healthcare-Associated Pneumonia and Hospital-Acquired Pneumonia: Bacterial Aetiology, Antibiotic Resistance and Treatment Outcomes: A Study From North India.

BACKGROUND: Data regarding the comparative profiling of HCAP and HAP from developing countries like India are scant. We set out to address the microbial aetiology, antibiotic resistance and treatment outcomes in patients with HCAP and HAP. METHODS: 318 consenting patients with HCAP (n = 165, aged 16-90 years; median 60 years; 97 males) or HAP (n = 153; aged 16-85 years; median 45 years; 92 males) presenting to a tertiary care hospital in North India from 2013 to 2015 were prospectively recruited for the study. Data on patient characteristics, microbial aetiology, APACHE II scores, treatment outcomes and mortality were studied. Clinical outcomes were compared with various possible predictors employing logistic regression analysis. RESULTS: Patients in HCAP had more comorbidity. Escherichia coli (30, 18%) and Acinetobacter baumannii (62, 41%) were the most commonly isolated bacteria in HCAP and HAP, respectively. Multidrug-resistant bacteria were isolated more frequently in HCAP, only because the incidence of extensively drug-resistant bacteria was markedly high in HAP (p = 0.00). The mean APACHE II score was lower in HCAP (17.55 ± 6.406, range 30) compared to HAP (19.74 ± 8.843, range 37; p = 0.013). The length of stay ≥ 5 days (p = 0.036) and in-hospital mortality was higher in HAP group (p = 0.002). The most reliable predictors of in-hospital mortality in HCAP and HAP were APACHE II score ≥ 17 (OR = 14, p = 0.00; HAP: OR = 10.8, p = 0.00), and septic shock (OR = 4.5, p = 0.00; HAP: OR = 6.9, p = 0.00). CONCLUSION: The patient characteristics in HCAP, treatment outcomes, bacterial aetiology, and a higher incidence of antibiotic-resistant bacteria, suggest that HCAP although not as severe as HAP, can be grouped as a separate third entity.

NDM-1 (New Delhi metallo beta lactamase-1) producing Gram-negative bacilli: emergence & clinical implications.

UNLABELLED: BACKGOUND & OBJECTIVES: Resistance to carbapenems in Gram-negative bacteria conferred by NDM-1 is a global health problem. We investigated the occurrence of NDM-1 in clinical isolates of Gram-negative bacilli in a tertiary care hospital in Kashmir valley, India. METHODS: Gram-negative bacilli from different clinical isolates were included in the study. Antimicrobial susceptibility was performed by Kirby Bauer disk diffusion method and interpreted using Clinical Laboratory Standards Institute (CLSI) guidelines. Isolates resistant to carbapenems were subjected to different phenotypic test such as modified Hodge test (MHT), boronic acid and oxacillin based MHT ( BA-MHT and OXA-MHT), combined disk test and minimum inhibitory concentration (MIC) with imipenem and imipenem -EDTA for determination of class B metallo enzymes. Presence of blaNDM-1 gene was established by PCR and confirmed by sequencing. RESULTS: Of the total 1625 Gram-negative isolates received, 100 were resistant to imipenem. Of the 100 isolates, 55 (55%) were positive by modified Hodge test indicating carbapenemase production. Of the 100 isolates tested by MHT, BA-MHT and OXA-MHT, 29 (29%) isolates belonged to Class A and 15 (15%) to Class B, while 56 (56%) isolates were negative. Of the 15 class B metallo beta lactamase producers, nine carried the bla(NDM-1) gene. NDM-1 was found among Escherichia coli (2 isolates), Klebsiella pneumoniae (2 isolates), Citrobacter freundii (3 isolates), Acinetobacter spp (1 isolate), and one isolate of Pseudomonas aeruginosa. Isolates were resistant to all antibiotic tested except polymyxin B and tigecycline. INTERPRETATION & CONCLUSIONS: Our study showed the presence of clinical isolates expressing NDM-1 in Srinagar, Jammu & Kashmir, India. These isolates harbour plasmid mediated multiple drug resistant determinants and can disseminate easily across several unrelated genera. To halt their spread, early identification of these isolates is mandatory.

Rapid detection of drug-resistant Mycobacterium tuberculosis by Modified MODS assay suitable for resource-poor settings.

BACKGROUND: Cross contamination and biosafety are concerns with the microscopic observation drug susceptibility assay. To address these issues, we modified the MODS technique in the current study. METHODOLOGY/PRINCIPAL FINDINGS: Two hundred and seventy-five samples were processed on LJ media and drug susceptibility was performed by the Indirect agar proportion method. A modified MODS test was done in tissue culture bottles. GenoType MTBDRplus assay was performed to detect the resistance and mutational pattern associated with the resistances. Sensitivity, specificity, positive predictive value, and negative predictive value for the detection of tuberculosis by modified MODS were 97.44%, 80.00%, 97.44%, and 80.00% respectively. The perfect agreement was seen between modified MODS and the Indirect agar proportion method for drug susceptibility testing of isoniazid (kappa = 0.923) and rifampicin (kappa = 1). The contamination rate, cost and TAT for modified MODS were less as compared to the solid media. In the case of MDR-TB isolates S531L (66.66%) was the most prevalent mutation in the rpoB gene followed by S315T2 mutation (58.33%) and T8C (41.66%) in katG and inhA gene respectively. In hetero-resistant strains, C-15T mutation (37.50%) was the most common followed by A-16G (12.50%) in the inhA gene. In INH mono-resistant strains only two mutations were observed i.e., S-315T1(50%) and C-15T (50%) in the katG and inhA genes respectively. CONCLUSIONS/SIGNIFICANCE: Modified MODS proved to be cost-effective and user-friendly, with minimal risk to the handler and no cross-contamination between samples were observed. Hence, it can be used in low-income countries for early detection of tuberculosis and its resistance.

An outbreak of Burkholderia cepacia bloodstream infections in a tertiary-care facility in northern India detected by a healthcare-associated infection surveillance network.

OBJECTIVE: The burden of healthcare-associated infections (HAIs) is higher in low- and middle-income countries, but HAIs are often missed because surveillance is not conducted. Here, we describe the identification of and response to a cluster of Burkholderia cepacia complex (BCC) bloodstream infections (BSIs) associated with high mortality in a surgical ICU (SICU) that joined an HAI surveillance network. SETTING: A 780-bed, tertiary-level, public teaching hospital in northern India. METHODS: After detecting a cluster of BCC in the SICU, cases were identified by reviewing laboratory registers and automated identification and susceptibility testing outputs. Sociodemographic details, clinical records, and potential exposure histories were collected, and a self-appraisal of infection prevention and control (IPC) practices using assessment tools from the World Health Organization and the US Centers for Disease Control and Prevention was conducted. Training and feedback were provided to hospital staff. Environmental samples were collected from high-touch surfaces, intravenous medications, saline, and mouthwash. RESULTS: Between October 2017 and October 2018, 183 BCC BSI cases were identified. Case records were available for 121 case patients. Of these 121 cases, 91 (75%) were male, the median age was 35 years, and 57 (47%) died. IPC scores were low in the areas of technical guidelines, human resources, and monitoring and evaluation. Of the 30 environmental samples, 4 grew BCC. A single source of the outbreak was not identified. CONCLUSIONS: Implementing standardized HAI surveillance in a low-resource setting detected an ongoing Burkholderia cepacia outbreak. The outbreak investigation and use of a multimodal approach reduced incident cases and informed changes in IPC practices.

The 2022 outbreak and the pathobiology of the coxsackie virus [hand foot and mouth disease] in India.

Outbreaks of HFMD in children aged <5 years have been reported worldwide and the major causative agents are Coxsackievirus (CV) A16, enterovirus (EV)-A71 and recently CVA6. In India, HFMD is a disease that is not commonly reported. The purpose of the study was to identify the enterovirus type(s) associated with large outbreak of Hand, foot, and mouth disease during COVID-19 pandemic in 2022. Four hundred and twenty five clinical samples from 196-suspected cases were collected from different parts of the country. This finding indicated the emergence of CVA6 in HFMD along with CVA16, soon after the gradual easing of non-pharmaceutical interventions during-pandemic COVID-19 and the relevance of continued surveillance of circulating enterovirus types in the post-COVID pandemic era.

Pan-India influenza-like illness (ILI) and Severe acute respiratory infection (SARI) surveillance: epidemiological, clinical and genomic analysis.

Background: Over time, COVID-19 testing has significantly declined across the world. However, it is critical to monitor the virus through surveillance. In late 2020, WHO released interim guidance advising the use of the existing Global Influenza Surveillance and Response System (GISRS) for the integrated surveillance of influenza and SARS-CoV-2. Methods: In July 2021, we initiated a pan-India integrated surveillance for influenza and SARS-CoV-2 through the geographically representative network of Virus Research and Diagnostic Laboratories (VRDLs) across 26 hospital and laboratory sites and 70 community sites. A total of 34,260 cases of influenza-like illness (ILI) and Severe acute respiratory infection (SARI) were enrolled from 4 July 2021 to 31 October 2022. Findings: Influenza A(H3) and B/Victoria dominated during 2021 monsoon season while A(H1N1)pdm09 dominated during 2022 monsoon season. The SARS-CoV-2 "variants of concern" (VoC) Delta and Omicron predominated in 2021 and 2022, respectively. Increased proportion of SARI was seen in extremes of age: 90% cases in < 1 year; 68% in 1 to 5 years and 61% in ≥ 8 years age group. Approximately 40.7% of enrolled cases only partially fulfilled WHO ILI and SARI case definitions. Influenza- and SARS-CoV-2-infected comorbid patients had higher risks of hospitalization, ICU admission, and oxygen requirement. Interpretation: The results depicted the varying strains and transmission dynamics of influenza and SARS-CoV-2 viruses over time, thus emphasizing the need to continue and expand surveillance across countries for improved decision making. The study also describes important information related to clinical outcomes of ILI and SARI patients and highlights the need to review existing WHO ILI and SARI case definitions.

A self-reported survey on the implementation of infection prevention and control elements in Indian hospitals, part of a HAI surveillance network: Results from 23 hospitals conducting a standardized IPC assessment.

BACKGROUND: Healthcare-associated infections (HAIs) are one of the most common adverse events in patient care that account for substantial morbidity and mortality. We evaluate the existing Infection Prevention and Control (IPC) practices in hospitals participating in the nationally representative HAI Surveillance network. METHODS: This cross-sectional survey was conducted in 23 hospitals across 22 states of India from October-2015 to September-2018 in the HAI surveillance network. The World Health Organization (WHO) IPC core components assessment tool for health-care facility level (IPCAT-H) was adapted from IPC assessment tool developed by US Centers for Disease Control and Prevention (US CDC) under the Epidemiology and Laboratory Capacity (ELC) Infection Control Assessment and Response (ICAR) Program. Mann-Whitney U test was used to calculate the significant difference between scores (P < .05). RESULTS: Amongst the participating hospitals, 7 were private sectors and 16 were public health care facilities. Infection IPCAT-H average score per multimodal strategy was less than 50% for programmed IPC activities (45.7); implementation of health care workers (HCWs) immunization programme (43.5%); monitoring and evaluation component (38.30%). CONCLUSIONS: There is potential for improvement in Human Resources, Surveillance of HAIs as well as Monitoring and Evaluation components.

Evaluation of various phenotypic methods for differentiation of Candida dubliniensis from Candida albicans.

INTRODUCTION: Candida dubliniensis was first identified by Sullivan et al. (1995) in Dublin, Ireland. Its clinical significance is associated with development of fluconazole-resistance and invasive diseases in immunocompromised hosts. C. dubliniensis share many features with C. albicans so has been overlooked and misidentified for a long time. AIMS: Evaluation of various phenotypic tests with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) as a gold standard to find out the best method/methods for identifying C. dubliniensis. MATERIALS AND METHODS: First PCR-RFLP was performed on 186C. albicans and 14C. dubliniensis strains and then five phenotypic tests were performed simultaneously on all the strains. RESULTS: The results of salt tolerance test at 48 h, colony color on HiCrome candida differential agar (HCDA) at 72 h, heat tolerance test at 48 h, xylose assimilation using discs at 72 h and growth on xylose based agar medium (XAM) at 48 h are completely concordant with PCR-RFLP. Colony color on Tobacco agar could differentiate accurately 100% test strains while peripheral hyphal fringes and chlamydosporulation on this agar was seen in only 86% and 87% respectively. Our routine methods proved to be cost effective than PCR-RFLP but the turnaround time was same or more than PCR-RFLP. CONCLUSION: For routine identification of C. dubliniensis we recommend use of colony color on HCDA and growth on XAM as simple, reliable and inexpensive method.

Comparative evaluation of serological tests used for the diagnosis of rickettsial diseases prevalent in the temperate region of North India.

PURPOSE: The clinical manifestations of rickettsial diseases mimic other endemic infections with similar presentations thus posing a serious challenge to clinicians for their diagnosis. For the diagnosis of rickettsial disease serological tests like Weil Felix, ELISA and IFA are used. There are limited studies that have evaluated different serological tests for the diagnosis of rickettsial diseases. Therefore, the present study was undertaken to evaluate the ELISA and Weil Felix test for the diagnosis of rickettsial diseases prevalent in this region. METHODS: Samples from 281 patients clinically suspected of rickettsial diseases were tested for spotted fever group (SFG), typhus group (TG) and scrub typhus group (STG) by Weil Felix, ELISA and IFA was taken as the gold standard. Baseline titers and cut-off ODs were calculated by taking samples from healthy blood donors. RESULTS: The sensitivity, specificity, positive and negative predictive value of Weil Felix test ranged from 30% to 44%, 83.46%-97.86%, 9%-77%, 92-96% respectively. The sensitivity and specificity, positive and negative predictive value of ELISA ranged from 80.77% to 96.15%, 96.33%-98.43%, 70.21%-88.64%, 92.89%-99.60% respectively. Maximum cross-reactions were observed between SFG and STG by the Weil Felix test and between STG and TG by ELISA. CONCLUSIONS: ELISA was found to be sensitive and specific for the diagnosis of rickettsial diseases. It is easy to perform, does not require a technical expert for result interpretation and a large number of samples can be processed at a time.

Health-care-associated bloodstream and urinary tract infections in a network of hospitals in India: a multicentre, hospital-based, prospective surveillance study.

BACKGROUND: Health-care-associated infections (HAIs) cause significant morbidity and mortality globally, including in low-income and middle-income countries (LMICs). Networks of hospitals implementing standardised HAI surveillance can provide valuable data on HAI burden, and identify and monitor HAI prevention gaps. Hospitals in many LMICs use HAI case definitions developed for higher-resourced settings, which require human resources and laboratory and imaging tests that are often not available. METHODS: A network of 26 tertiary-level hospitals in India was created to implement HAI surveillance and prevention activities. Existing HAI case definitions were modified to facilitate standardised, resource-appropriate surveillance across hospitals. Hospitals identified health-care-associated bloodstream infections and urinary tract infections (UTIs) and reported clinical and microbiological data to the network for analysis. FINDINGS: 26 network hospitals reported 2622 health-care-associated bloodstream infections and 737 health-care-associated UTIs from 89 intensive care units (ICUs) between May 1, 2017, and Oct 31, 2018. Central line-associated bloodstream infection rates were highest in neonatal ICUs (>20 per 1000 central line days). Catheter-associated UTI rates were highest in paediatric medical ICUs (4·5 per 1000 urinary catheter days). Klebsiella spp (24·8%) were the most frequent organism in bloodstream infections and Candida spp (29·4%) in UTIs. Carbapenem resistance was common in Gram-negative infections, occurring in 72% of bloodstream infections and 76% of UTIs caused by Klebsiella spp, 77% of bloodstream infections and 76% of UTIs caused by Acinetobacter spp, and 64% of bloodstream infections and 72% of UTIs caused by Pseudomonas spp. INTERPRETATION: The first standardised HAI surveillance network in India has succeeded in implementing locally adapted and context-appropriate protocols consistently across hospitals and has been able to identify a large number of HAIs. Network data show high HAI and antimicrobial resistance rates in tertiary hospitals, showing the importance of implementing multimodal HAI prevention and antimicrobial resistance containment strategies. FUNDING: US Centers for Disease Control and Prevention cooperative agreement with All India Institute of Medical Sciences, New Delhi. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Self-reported survey on infection prevention and control structures in healthcare facilities part of a national level healthcare associated infection surveillance network in India, 2019.

BACKGROUND: Healthcare associated infections (HAIs) are prevalent and difficult to treat worldwide. Most HAIs can be prevented by effective implementation of Infection Prevention and Control (IPC) measures. A survey was conducted to assess the existing IPC practices across a network of Indian Hospitals using the World Health Organization designed self-assessment IPC Assessment Framework (IPCAF) tool. METHODS: This was a cross sectional observation study. Thirty-two tertiary care public and private facilities, part of the existing Indian HAI surveillance network was included. Data collected was analyzed by a central team at All India Institute of Medical Sciences, New Delhi, a tertiary care hospital of India. The WHO questionnaire tool was used to understand the capacity and efforts to implement IPC practices across the network. RESULTS: The overall median score of IPCAF across the network was 620. Based on the final IPCAF score of the facilities; 13% hospitals had basic IPC practices, 28% hospitals had intermediate and 59% hospitals had advanced IPC practices. The component multimodal strategies had the broadest range of score while the component IPC guidelines had the narrowest one. CONCLUSIONS: Quality improvement training for IPC nurses and healthcare professionals are needed to be provided to health facilities.

Prevalence, clinical profile and follow up of asymptomatic bacteriuria in patients with type 2 diabetes-prospective case control study in Srinagar, India.

BACKGROUND AND AIMS: Asymptomatic bacteriuria (ASB) is more prevalent in diabetes mellitus (DM) patients than non diabetics, but its significance is not fully known. This study was done to estimate the prevalence, clinical profile, risk factors and follow up of ASB in type 2 diabetes (T2D) patients compared with matching healthy controls. METHODS: Prospective, case-control study involving 400 T2D patients without symptoms of urinary tract infection (UTI) and 200 age and sex matched healthy controls. Apart from clinical and biochemical parameters, samples for urine examination and culture were taken from all the subjects. ASB was defined as ≥105 colony-forming units/ml of one or two organisms in the absence of symptoms of UTI. RESULTS: The prevalence of ASB was significantly higher in T2D (17.5%) as compared to controls (10%). E. coli was the most common organism. On multivariate analysis, postmenopausal state, prior history of UTI, uncontrolled diabetes and longer duration of disease were associated with increased risk of ASB. Presence of ASB was significantly associated with symptomatic UTI at the 6-month follow up without deterioration of renal parameters. CONCLUSIONS: Asymptomatic bacteriuria was more prevalent in people with diabetes than those without diabetes. The presence of ASB may be considered a risk factor for subsequent symptomatic UTI on follow up but has no adverse effect on kidney function.

Rickettsial Infections among the Undifferentiated Febrile Patients Attending a Tertiary Care Teaching Hospital of Northern India: A Longitudinal Study.

BACKGROUND: Acute undifferentiated febrile illness (AUFI) is one of the most daunting challenges a physician faces in such settings. Among AUFI, rickettsial infections are most common and related infections (such as anaplasmosis, ehrlichiosis, and Q fever) which are caused by an unusual type of bacteria that can live only inside the cells of another organism. The present study was therefore planned with an objective to estimate the prevalence of rickettsial infection among patients of undifferentiated fever and to determine any association of socio-demographic characteristics with rickettsial disease. MATERIALS AND METHODS: Patients presenting with febrile illness and admitted or attending out-patient department of Sher-i-Kashmir Institute of Medical Sciences, Srinagar was approached and recruited in the study. Weil Felix Assay, enzyme-linked immunosorbent assay and indirect immunofluorescence assay were done to detect the anti-rickettsial antibodies. Serological evidence of a fourfold increase in IgG-specific antibody titer reactive with spotted fever group rickettsial antigen by indirect immunofluorescence antibody assays between paired serum specimens was considered a confirmatory diagnosis for the rickettsial disease. RESULTS: Most of the patients were males 61.6%, and most 46.2% were in the age group of 20 -39 years. Most of the patients, 80.8% belonged to rural areas, and 48% belonged to the upper middle (II) class of the socio-economic class according to modified Kuppuswamy scale. Of the studied participants, a majority, 47.0%, were determined undiagnosed, while 15.4% studied participants were diagnosed to have a rickettsial disease. In patients positive for typhus group, 67.8% were IgM positive, 28.5% were IgG positive, and only 3% were positive for IgM and IgG. In patients positive for Scrub Typhus Group, 32.7% were positive for IgM, and 62.0% were positive for IgG, and only 5.0% were positive for both IgM and IgG. In patients positive for spotted fever group, 36.1% were positive for IgM, and 58.5% were positive for IgG, and only 5.5% were positive for both IgM and IgG. The prevalence of rickettsial disease was found to be 11.3%. CONCLUSION: Rickettsial diseases, typhoid and brucellosis, were the most prevalent diseased diagnosed among patients reporting to hospitals with undifferentiated febrile illness. Clinicians must consider rickettsial diseases as one of the differential diagnosis while treating patients with fever.

Clinical Characterization and Genomic Analysis of Samples from COVID-19 Breakthrough Infections during the Second Wave among the Various States of India.

From March to June 2021, India experienced a deadly second wave of COVID-19, with an increased number of post-vaccination breakthrough infections reported across the country. To understand the possible reason for these breakthroughs, we collected 677 clinical samples (throat swab/nasal swabs) of individuals from 17 states/Union Territories of the country who had received two doses (n = 592) and one dose (n = 85) of vaccines and tested positive for COVID-19. These cases were telephonically interviewed and clinical data were analyzed. A total of 511 SARS-CoV-2 genomes were recovered with genome coverage of higher than 98% from both groups. Analysis of both groups determined that 86.69% (n = 443) of them belonged to the Delta variant, along with Alpha, Kappa, Delta AY.1, and Delta AY.2. The Delta variant clustered into four distinct sub-lineages. Sub-lineage I had mutations in ORF1ab A1306S, P2046L, P2287S, V2930L, T3255I, T3446A, G5063S, P5401L, and A6319V, and in N G215C; Sub-lineage II had mutations in ORF1ab P309L, A3209V, V3718A, G5063S, P5401L, and ORF7a L116F; Sub-lineage III had mutations in ORF1ab A3209V, V3718A, T3750I, G5063S, and P5401L and in spike A222V; Sub-lineage IV had mutations in ORF1ab P309L, D2980N, and F3138S and spike K77T. This study indicates that majority of the breakthrough COVID-19 clinical cases were infected with the Delta variant, and only 9.8% cases required hospitalization, while fatality was observed in only 0.4% cases. This clearly suggests that the vaccination does provide reduction in hospital admission and mortality.

An Epidemiological Analysis of SARS-CoV-2 Genomic Sequences from Different Regions of India.

The number of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) cases is increasing in India. This study looks upon the geographic distribution of the virus clades and variants circulating in different parts of India between January and August 2020. The NPS/OPS from representative positive cases from different states and union territories in India were collected every month through the VRDLs in the country and analyzed using next-generation sequencing. Epidemiological analysis of the 689 SARS-CoV-2 clinical samples revealed GH and GR to be the predominant clades circulating in different states in India. The northern part of India largely reported the 'GH' clade, whereas the southern part reported the 'GR', with a few exceptions. These sequences also revealed the presence of single independent mutations-E484Q and N440K-from Maharashtra (first observed in March 2020) and Southern Indian States (first observed in May 2020), respectively. Furthermore, this study indicates that the SARS-CoV-2 variant (VOC, VUI, variant of high consequence and double mutant) was not observed during the early phase of virus transmission (January-August). This increased number of variations observed within a short timeframe across the globe suggests virus evolution, which can be a step towards enhanced host adaptation.

Phenotypic detection of constitutive and inducible clindamycin resistance in clinical isolates of Staphylococcus aureus and coagulase negative Staphylococcus on routine susceptibility plate.

Increasing frequency of methicillin resistant Staphylococcus aureus infections and changing patterns in antimicrobial resistance have led to renewed interest in the use of macrolidelincosamide-streptogramin antibiotics. However therapy may fail either due to constitutive or inducible resistance. This study was undertaken to detect different phenotypes including inducible clindamycin resistance in clinical isolates of Staphylococcus aureus and coagulase negative Staphylococcus. Four hundred sixty five Staphylococcus aureus and 84 coagulase negative Staphylococci isolated from different clinical specimens were included in the study. On routine susceptibility testing plate clindamycin (2 microg) disk was placed at a distance of 15mm towards the centre from a peripherally placed erythromycin (15 microg) disk. Fisher exact test was used for statistical analysis. Out of 465 Staphylococcus aureus isolates, 237 (50.96%) were methicillin sensitive (MSSA) and 228 (49.03%) methicillin resistant (MLS(B)c).Over all 118 (25.37%) isolates showed constitutive resistance (MLS(B)c), 70 (15.05%) inducible clindamycin resistance, 143 (30.75%) MS(B) phenotype and 134 (28.81%) were susceptible to both erythromycin as well as clindamycin. Constitutive and inducible resistance to clindamycin were significantly higher in MRSA than MSSA (P=0.0000 and 0.0001 respectively). Out of 84 isolates of coagulase negative Staphylococci, 43 (51.19%) were methicillin sensitive (MSCNS) and 41(48.80%) methicillin resistant (MRCNS). Constitutive MLS(B) resistance was detected in 32 (38.09%), inducible clindamycin resistance 10 (11.90%), MS(B) phenotype 27 (32.14%) and 15 (17.85%) were susceptible to both erythromycin and clindamycin. Performing D test on a routine susceptibility plate saves material, manpower and time as inducible resistance can be reported simultaneously along with other susceptibility results.

Fungal endophthalmitis: fourteen years' experience from a center in India.

BACKGROUND: As fungal endophthalmitis is an emerging challenge, the study was carried out to determine the prevalence and the spectrum of fungal agents causing endophthalmitis from a single center, to identify the risk factors, and to correlate clinical course of illness with the agents involved. METHODS: The microbiological and clinical records of all fungal endophthalmitis diagnosed during January 1992 through December 2005 at a tertiary center in India were reviewed retrospectively. During this period, treatment protocol of the patients with fungal endophthalmitis was pars plana vitrectomy, instillation of intravitreal amphotericin B (5 microg) and dexamethasone (400 microg). Additionally, oral fluconazole (27 patients) or itraconazole (78 patients) was given in 105 patients. RESULTS: Fungal endophthalmitis was diagnosed in 113 patients and they were categorized into: postcataract surgery (53 patients), posttrauma (48), and endogenous (12) groups. Aspergillus species was the most common (54.4%) agent isolated, followed by yeasts (24.6%), and melanized fungi (10.5%). Among Aspergilli, Aspergillus flavus was the most common (24.6%) species whereas Candida tropicalis (8.8%) was in the yeast. Other rare agents isolated include Fonsecaea pedrosoi, Fusarium solani, Paecilomyces lilacinus, Pseudallescheria boydii, Colletotrichum dematium, Cryptococcus neoformans, and Trichosporon cutaneum. Visual acuity after therapy remained <20/400 in 77.4%, 64.3%, 50.0%, and 16.7% patients infected with Aspergillus species, yeasts, melanized fungi and other mycelial fungi, respectively. The outcome was unfavorable in 52.8%, 66.7%, and 33.3% patients with postoperative, posttrauma, and endogenous groups, respectively. CONCLUSIONS: This study is the largest series of fungal endophthalmitis from a single center and highlights the fact that a vast array of fungi can cause endophthalmitis though Aspergilli are the common agents. The combination of pars plana vitrectomy and intravitreal amphotericin B with or without fluconazole/itraconazole was the common mode of therapy in such patients. However, the main challenge is suspecting fungal etiology at the time of presentation and accurately diagnosing those patients.