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July-September 2019
Volume 37 | Issue 3
Page Nos. 299-458

Online since Wednesday, January 29, 2020

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REVIEW ARTICLE  

Topical antimicrobial therapy: Current status and challenges Highly accessed article p. 299
Pallab Ray, Shreya Singh, Swati Gupta
DOI:10.4103/ijmm.IJMM_19_443  PMID:32003326
Topically applied antibacterial agents are widely used. Opinions regarding the clinical efficacy of topical antibiotics are conflicting, and for most indications, alternative oral therapies are available. Topical application has many potential advantages over systemic therapy that includes high and sustained concentrations of drug directly at the infected site, low quantity of antibiotic needed, better compliance, fewer systemic side effects and potentially less chance of antimicrobial resistance. Despite these advantages, an important concern has been the difficulty in monitoring antibiotic dosage and duration of therapy. Most topical preparations are applied on sites with pre-existing normal bacterial flora, and the detrimental effect of antibiotic on the 'good' bacteria is difficult to control. Unnecessary exposure of the resident microflora to high drug levels may select drug-resistant phenotypes. The number of antibiotics available and the quality and composition of the formulations recommended for topical drug delivery are improving. Their role in the prevention and treatment of locally invasive infections is established for many clinical conditions. However, there is still a lacuna in the availability of pharmacokinetic (PK) knowledge of these topical preparations and translation of the same to clinical practice. In addition, reporting the clinical outcome following the use of these agents and its analysis considering the recently proposed epidemiological cut-off value-based cut-offs are also areas which merit further research. In this review, we highlight the clinical utility and the PK aspects of topical antimicrobials in various infections. We also discuss the limitations of the current antimicrobial susceptibility testing (AST) protocols and new methods for AMST for topical agents.
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ORIGINAL ARTICLES Top

Assessment of core capacities for antimicrobial stewardship practices in indian hospitals: Report from a multicentric initiative of global health security agenda p. 309
Mathur Purva, Guleria Randeep, Malhotra Rajesh, C Misra Mahesh, Gupta Sunil, Kumar Subodh, Sagar Sushma, Wig Naveet, Garg Pramod, Kapil Arti, Khurana Surbhi, Katoch Omika, Katyal Sonal, Sahu Manoj, Chakrabarti Arunaloke, Ray Pallab, Biswal Manisha, Taneja Neelam, Rupali Priscilla, K Subaramani, Jacob Ebor, Balaji Veeraraghavan, Rodrigues Camilla, Nag Vijayalakshmi, Tak Vibhor, Singh Kuldeep, K Bhatia Pradeep, Gupta Neeraj, Khera Daisy, Venkatesh Vimala, Mukhopadhyay Chiranjay, KE Vandana, Varma Muralidhar, Deotale Vijayshri, Attal Ruchita, Padmaja Kanne, Sudhaharan Sukanya, Wattal Chand, Goel Neeraj, Bhattacharya Sanjay, Sen Sourav, Tadepalli Karuna, Saigal Saurabh, Bijayini Behera, Singh Sanjeev, MA Thirunarayan, Nath Reema, Saikia Lahri, Ray Raja, J Raj Hirak, Baveja Sujata, D'Souza Desma, Chandy Mammen, Mukherjee Sudipta, K Roy Manas, Goel Gaurav, Tripathy Swagata, Misra Satyajeet, Dey Anupam, S Mishra Tushar, A Fomda Bashir, Bashir Gulnaz, Nazir Shaista, Devi Sulochana, R Devi Khuraijam, C Singh Langpoklakpam, Das Padma, Bhargava Anudita, Gaikwad Ujjwala, Khandelwal Neeta, Vaghela Geeta, Sukharamwala Tanvi, Jain Shristi, Verma Prachi, Lamba Mamta, Bhattacharyya Prithwis, C Phukan Anil, Lyngdoh Clarissa, Gaind Rajni, Saksena Rushika, Kapoor Lata, Ohri Vinod, Walia Kamini
DOI:10.4103/ijmm.IJMM_19_445  PMID:32003327
Introduction: Antimicrobial-resistant HAI (Healthcare associated infection) are a global challenge due to their impact on patient outcome. Implementation of antimicrobial stewardship programmes (AMSP) is needed at institutional and national levels. Assessment of core capacities for AMSP is an important starting point to initiate nationwide AMSP. We conducted an assessment of the core capacities for AMSP in a network of Indian hospitals, which are part of the Global Health Security Agenda-funded work on capacity building for AMR-HAIs. Subjects and Methods: The Centers for Disease Control and Prevention's core assessment checklist was modified as per inputs received from the Indian network. The assessment tool was filled by twenty hospitals as a self-administered questionnaire. The results were entered into a database. The cumulative score for each question was generated as average percentage. The scores generated by the database were then used for analysis. Results and Conclusion: The hospitals included a mix of public and private sector hospitals. The network average of positive responses for leadership support was 45%, for accountability; the score was 53% and for key support for AMSP, 58%. Policies to support optimal antibiotic use were present in 59% of respondents, policies for procurement were present in 79% and broad interventions to improve antibiotic use were scored as 33%. A score of 52% was generated for prescription-specific interventions to improve antibiotic use. Written policies for antibiotic use for hospitalised patients and outpatients were present on an average in 72% and 48% conditions, respectively. Presence of process measures and outcome measures was scored at 40% and 49%, respectively, and feedback and education got a score of 53% and 40%, respectively. Thus, Indian hospitals can start with low-hanging fruits such as developing prescription policies, restricting the usage of high antibiotics, enforcing education and ultimately providing the much-needed leadership support.
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Protocol for developing a surveillance system for surgical site infections p. 318
Purva Mathur, Samarth Mittal, Vivek Trikha, Ayush Lohiya, Surbhi Khurana, Sonal Katyal, Nidhi Bhardwaj, Sushma Sagar, Subodh Kumar, Rajesh Malhotra, Kamini Walia
DOI:10.4103/ijmm.IJMM_19_446  PMID:32003328
Purpose: Healthcare-associated infections (HCAIs/ HAIs) are the most common adverse occurrences during health care delivery. Across the globe, millions of patients are affected by HAIs annually, with a higher burden and impact in developing nations. a major lacuna in planning preventing protocols is the absence of National Surveillance Systems in most low-middle income countries, which also prevents allocation of resources to the high-priority areas. Among all the HAIs, there is a huge global burden of SSIs, in terms of morbidity, prolonged hospital stays, increased antimicrobial treatment as well as attributable mortality. Method: This manuscript details the process of establishment of an SSI surveillance protocol at a level-1 trauma centre in North India. Result and Conclusion: Surveillance is an essential tool to reduce this burden. It is also an important primary step in recognizing problems and priorities, and it plays a crucial role in identifying risk factors for SSI and to be able to target modifiable risk factors. Therefore, it is imperative to establish reliable systems for surveillance of HAIs, to regularly estimate the actual burden of HAIs, and to use these data for developing indigenous preventive measures, tailored to the country's priorities.
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Clonal clusters and virulence factors of methicillin-resistant Staphylococcus Aureus: Evidence for community-acquired methicillin-resistant Staphylococcus Aureus infiltration into hospital settings in Chennai, South India p. 326
Nagarajan Abimannan, G Sumathi, OR Krishnarajasekhar, Bhanu Sinha, Padma Krishnan
DOI:10.4103/ijmm.IJMM_18_271  PMID:32003329
Background and Objective: Staphylococcus aureus is one of the major pathogens of nosocomial infections as wells as community-acquired (CA) infections worldwide. So far, large-scale comprehensive molecular and epidemiological characterisation of S. aureus from very diverse settings has not been carried out in India. The objective of this study is to evaluate the molecular, epidemiological and virulence characteristics of S. aureus in both community and hospital settings in Chennai, southern India. Methods: S. aureus isolates were obtained from four different groups (a) healthy individuals from closed community settings, (b) inpatients from hospitals, (c) outpatients from hospitals, representing isolates of hospital–community interface and (d) HIV-infected patients to define isolates associated with the immunocompromised. Antibiotic susceptibility testing, multiplex polymerase chain reactions for detection of virulence and resistance determinants, molecular typing including Staphylococcal cassette chromosome mec (SCCmec) and agr typing, were carried out. Sequencing-based typing was done using spa and multilocus sequence typing (MLST) methods. Clonal complexes (CC) of hospital and CA methicillin-resistant S. aureus (MRSA) were identified and compared for virulence and resistance. Results and Conclusion: A total of 769 isolates of S. aureus isolates were studied. The prevalence of MRSA was found to be 7.17%, 81.67%, 58.33% and 22.85% for groups a, b, c and d, respectively. Of the four SCCmec types (I, III, IV and V) detected, SCCmec V was found to be predominant. Panton-Valentine leucocidin toxin genes were detected among MRSA isolates harbouring SCCmec IV and V. A total of 78 spa types were detected, t657 being the most prevalent. 13 MLST types belonging to 9 CC were detected. CC1 (ST-772, ST-1) and CC8 (ST238, ST368 and ST1208) were found to be predominant among MRSA. CA-MRSA isolates with SCCmec IV and V were isolated from all study groups including hospitalised patients and were found to be similar by molecular tools. This shows that CA MRSA has probably infiltrated into the hospital settings.
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Geographically distinct North-East Indian Helicobacter pylori strains are highly sensitive to clarithromycin but are levofloxacin resistant p. 337
Shweta Mahant, Amresh Kumar Sharma, Valentina Gehlot, Asish Kumar Mukhopadhyay, Ayushi Chhawchharia, Sangitanjan Dutta, Anil Agarwal, Anup Som, Kunal Das, Rajashree Das
DOI:10.4103/ijmm.IJMM_19_158  PMID:32003330
Purpose: Helicobacter pylori causes various gastro-intestinal diseases. Antibiotic resistance to commonly used antibiotics for the treatment of H. pylori infection is the major cause for treatment failure. The aim of this study is to determine the antimicrobial susceptibility pattern for clarithromycin and levofloxacin and find the evolutionary relationship of the partial sequence of 23S rRNA and gyraseA gene of H. pylori by phylogenetic analysis. Materials and Methods: A total of 46 H. pylori strains were tested for clarithromycin and levofloxacin susceptibility pattern and phylogenetic tree were reconstructed by PhyML software. Results: In this study, we observed that only 6.5% of North-East Indian H. pylori strains were resistant for clarithromycin showing mutation at A2143G and T2182C positions of 23S rRNA gene. Resistance for levofloxacin was observed in 89.1% of the H. pylori strains showing mutations at asparagine to lysine at 87 and aspartic acid to glycine/tyrosine/asparagine at 91 positions of gyraseA gene. The phylogenetic tree of the partial sequence of 23S rRNA and gyraseA gene depicts that the North-East Indian strains falls in different cluster when compared to other countries. Conclusions: Resistance for clarithromycin was less in North-East Indian strains but high for levofloxacin indicating that first-line therapy may be best and effective for eradication of H. pylori in this region. This study is the first report that showed antibiotic susceptibility pattern for clarithromycin and levofloxacin by mutation analysis. By partial sequencing of 23s rRNA and gyraseA gene, we found that North-East Indian strains are geographically distinct.
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Detection and molecular typing of campylobacter isolates from human and animal faeces in coastal belt of Odisha, India p. 345
Nirmal Kumar Mohakud, Saumya Darshana Patra, Subrat Kumar, Priyadarshi Soumyaranjan Sahu, Namrata Misra, Arpit Kumar Shrivastava
DOI:10.4103/ijmm.IJMM_19_394  PMID:32003331
Introduction: Campylobacter-mediated diarrhoea is one of the major causes of gastroenteritis globally. A majority of the Campylobacter spp. that cause disease in humans have been isolated from animals. Faecal contamination of food and water is the identified frequent cause of human campylobacteriosis. Methodology: In the present study, faecal samples from patients with symptoms of acute diarrhoea (n = 310) and domestic animals including cows (n = 60), sheep (n = 45) and goats (n = 45) were collected from the same localities in the peri-urban Bhubaneswar city. Genomic DNA isolation followed by polymerase chain reaction and sequencing was employed to analyse Campylobacter spp.-positive samples. Results: Of the 460 faecal samples, 16.77% of human samples and 25.33% of animal samples were found to be positive for Campylobacter spp. Among animals, the isolation rate was highest in sheep followed by cows and goats with 9.33%, 8.66% and 7.33%, respectively. The highest number of Campylobacter-positive cases was diagnosed in infants of 2–5 years age. Concurrent infection of other pathogens in addition to Campylobacter spp. was frequently detected in the samples. Conclusion: The present study showed the incidence of Campylobacter infections in human and different animal species in and around Bhubaneswar, Odisha. The analysis suggested that domestic animals can be the potential sources for human campylobacteriosis in the region.
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Seroprevalence of Toxoplasmosis at a Tertiary Care Centre in North India from 2004 to 2014 p. 351
Abhishek Mewara, Shreya Singh, Sumeeta Khurana, Parakriti Gupta, Rakesh Sehgal
DOI:10.4103/ijmm.IJMM_19_327  PMID:32003332
Purpose: This study was carried out to determine the seroprevalence of anti-Toxoplasma gondii antibodies in different groups of patients at a tertiary care hospital in North India. Materials and Methods: Clinical and demographic data such as age and gender of patients who had undergone testing for the presence of anti-T. gondii IgG and IgM antibodies between January 2004 and October 2014 were retrospectively analysed. Results: Amongst the 8397 serum samples, an overall seropositivity of 21% (n = 1763) and IgG and IgM seropositivity of 5.7% (n = 481) and 15.3% (n = 1282) were respectively observed. Compared to the period of 2004–2012 (median seroprevalence: 23.6%), a decline in seropositivity to 9.7% in 2013 and 8.1% in 2014 was noted. A rising seroprevalence with age and a higher seroprevalence in females versus males (29.5%, n = 1179 vs. 13.3%, n = 584) were recorded. The highest seroprevalence was observed in suspected ocular toxoplasmosis (47.2%, n = 47), followed by neurological (26.8%, n = 77), human immunodeficiency virus/acquired immunodeficiency syndrome (18.9%, n = 267), post-transplant (17.1%, n = 12) and congenital (7.2%, n = 144) toxoplasmosis. In patients screened for Toxoplasma exposure, the seropositivity was 47.8% (n = 11) in transplant screening and 44.9% (n = 781) in antenatal screening. Conclusion: Toxoplasma infection is highly prevalent in the population of North India across various clinical categories of patients. Future studies focusing on continuous monitoring of seroprevalence trends and elucidation of the risk factors associated with seropositivity in more defined groups of patients are needed.
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Clonal similarities and sequence-type diversity of invasive and carriage Streptococcus pneumoniae in India among children under 5 Years p. 358
Rosemol Varghese, Ayyanraj Neeravi, Nithya Subramanian, B Pavithra, A Kavipriya, Jones Lionel Kumar, CP Girish Kumar, Yuvraj Jeyraman, G Karthik, Valsan P Verghese, Balaji Veeraraghavan
DOI:10.4103/ijmm.IJMM_19_348  PMID:32003333
Background: Pneumococcal pneumonia is one of the major causes of mortality in children less than 5 years in Asia, especially in India. Available PCVs have less serotype coverage in India compared to western countries. Moreover, the baseline pneumococcal serotype and sequence type data is limited and available data doesn't represent the entire India. With this background we aimed to characterize invasive and carriage isolates of S. pneumoniae from a tertiary care hospital in South India. Materials and Methods: A total of 221 S. pneumoniae isolates, invasive (n=138) and carriage (n=83) between the time period of 2012-2018 were included. Isolates was identified and confirmed using standard laboratory protocols. Serotyping was performed by Customized sequential multiplex PCR and MLST as described in www.pubmlst.org. Results: The major serotypes were 19F, 6B, 14, 6A and 19A and the sequence types (ST) were ST63, 236 and 230. Predominant STs in invasive was ST 63 whereas in carriage were ST4894 and 1701. High level ST diversity in carriage was observed. Majority of the STs were SLVs or DLVs of previously reported STs or PMEN clones. Phylogenetic analyses of the STs revealed gradual expansion of three PMEN CCs CC320, 63 and 230. Conclusion: The vaccine serotypes were the predominant ones found to be associated with IPD, PMEN clones, new STs and antimicrobial resistance. Accordingly, PCV13 is expected to provide invasive serotype coverage of 75% in Indian children less than 5 years. This study provides baseline serotype and sequence type data prior to the introduction of PCV in South India.
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Cross-country transport and isolation and identification of Streptococcus pneumoniae by use of alternate sources of blood supplemented media among laboratories in India p. 363
Satish Kumar Amarnath, Sangeeta Joshi, Madhuwanti N Abhyankar, Ranjeeta Adhikary, HB Beena, TD Chugh, KD Gandhi, Vivek Hittinahalli, VA Indumathi, Mukhopadhyay Rajavari, S Muralidharan, SS Rao, I Roy, N Saini
DOI:10.4103/ijmm.IJMM_19_82  PMID:32003334
Background: The isolation of S. pneumoniae (Sp) depends on specimen integrity / transport, media and expertise. The non-availability of sheep blood agar poses a challenge in identification of colonial morphology and identification in India. Methods: Laboratories processed swabs containing either pure Sp or Sp in mixed cultures with a second (confounding) bacterium shipped across the country in cold conditions. Duplicate set of swabs was shipped back to the central laboratory to assess the impact of shipping on culture viability. The identical swab was cultured on sheep, human blood and one additional agar plate used in the laboratory. Results: 46/60(77%) of cultures containing only Sp were correctly identified. In specimens where Sp was present in mixed culture, the proportion of isolates in which Sp was correctly identified varied, with most variability attributed to the particular confounding organism rather than the media. There was no discernible impact of temperature-controlled (4-6°C) transport on the isolation of Sp from culture swabs. Conclusions: The study clearly elucidates the ability of laboratories for isolation of S. pneumoniae on human blood agar in resource limited settings. The results highlight the difficulties inherent in correctly identifying pathogens in mixed cultures in needs improvement using standardized tests across the study centers. The study also reaffirms the ability to transport biological specimens over long geographical distances without loss.
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Frequencies of regulatory subsets of CD4+ TH cells in peripheral blood in Mycobacterium Tuberculosis-Infected individuals and healthy contacts in a high-burden setting from Assam, Northeast India p. 370
Lahari Saikia, Trinayan Deka, Pranjal Deori, Rasmi Roy, Md Ezaz Hussain, Reema Nath
DOI:10.4103/ijmm.IJMM_18_439  PMID:32003335
Background: Mycobacterium tuberculosis (Mtb) adapts many strategies to persist and replicate inside human tissue. One such strategy is the manipulation of CD4+ TH cells for subset interconversion to regulatory subsets. The aim of the present study is to get an insight of dynamic changes of CD4+ TH cells to regulatory subsets, CD4+ CD25+ forkhead box P3 (Foxp3)+ T-cells and CD4+ CD25+ Foxp3+ programmed death molecule-1 (Foxp3+) T-cells, in peripheral blood in Mtb-infected individuals and healthy contacts in a high-burden setting from Assam, Northeast India. Materials and Methods: A case–control study was conducted in newly diagnosed active pulmonary tuberculosis (APTBs) patients and 2 sets of controls: (i) individuals infected with latent tuberculosis infection (LTBI) and (ii) healthy close tuberculosis healthy contacts (HCs). The frequencies of different subsets of CD4+ cells with regulatory markers were measured in peripheral blood in 3 groups of study participants. Results and Observations: Frequencies of CD4+ CD25+ Foxp3+ T-cells (1.84 ± 1.40 vs. 4.32 ± 1.82 vs. 11.30 ± 3.66), CD4+ CD25+ Foxp3+ PD1+ T-cells (0.37 ± 1.28 vs. 2.99 ± 3.69 vs. 14.54 ± 5.10) and ligand (PD-L1)-positive CD4+ TH cells (0.80 ± 0.45 vs. 2.28 ± 0.95 vs. 7.13 ± 2.02) were significantly increased from HCs to LTBIs to APTB patients, respectively (P < 0.0001). No significant changes in frequencies of total CD4+ cells were observed between APTBs (29.51 ± 11.93), LTBIs (29.23 ± 8.16) and HCs (28.16 ± 9.73) whereas the mean ratios of CD4+ to CD4+ CD25+ FoxP3+ were significantly decreased from 34.34 ± 47.56 in HCs to 7.96 ± 5.8 in LTBIs to 3.12 ± 2.58 in APTBs (P < 0.0001). Significant decrease in mean ratios of CD4+ CD25+ FoxP3+ to CD4+ CD25+ FoxP3+ PD1+ were also observed from 4.97 ± 1.09 in HCs to 1.44 ± 0.49 in LTBIs to 0.78 ± 0.72 in APTBs. Conclusion: CD4+ TH cells change dynamically to regulatory subsets depending on the status of infection and a shift of response towards excessive regulatory T-cells, and PD-1/PD-L1 production may help in the development of active infection in latently infected individuals. These immunological parameters may be used, as potential biomarkers to see the changing dynamics of Mtb infection.
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Central line-associated bloodstream infections in cancer patients: An experience from a tertiary care cancer centre p. 376
Sonu Kumari Agrawal, Hitender Gautam, Abdul Hakim Choudhary, Bimal Kumar Das, Lalit Kumar, Arti Kapil
DOI:10.4103/ijmm.IJMM_19_352  PMID:32003336
Introduction: Central venous catheters (CVCs) implanted in patients with malignancies may often be associated with local or central line-associated bloodstream infections (CLABSI), which are a major source of morbidity and rarely mortality, making such patients' care difficult and complicated. Materials and Methods: This retrospective study is a single-centre's experience including both paediatric and adult patients with malignancy, who had a CVC inserted and were receiving care at cancer centre of our hospital over a period between January 2017 and June 2018. Results: In the period from January 2017 to June 2018, 73 confirmed cases of CLABSIs among cancer patients were included in this study. The rate of CLABSIs was estimated as 2.1 episodes/1000 CVC days. Out of 73 CLABSI cases, Gram-negative bacilli were the predominant causative agents of CLABSI constituting 72.6% (n = 53/73) of isolated organisms, 21.9% (n = 16/73) of infections were caused by Gram-positive cocci while polymicrobial infections accounted for 5.4% (n = 4/73) of these cases. Conclusion: Over the last 20 years, an epidemiologic shift has occurred among CLABSI in cancer patients. These findings should be considered with the development of interventions that will prevent Gram-negative CLABSI after CVC insertion. To our knowledge, this is the first study reporting data on the incidence of CLABSIs in cancer patients at tertiary care hospital from North Indian hospital.
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Diagnostic performance of mini parasep® solvent-free foecal parasite concentrator for the diagnosis of intestinal parasitic infections p. 381
Abhishek Mewara, Sumeeta Khurana, Swati Gupta, Vimal S Munda, Shreya Singh, Rakesh Sehgal
DOI:10.4103/ijmm.IJMM_19_44  PMID:32003337
Introduction: Various stool concentration techniques have been used to increase the microscopic detection of parasites. We assessed the enclosed, single-vial, Mini Parasep® technique in comparison to the currently used coprodiagnosis procedures. Materials and Methods: A total of 150 stool samples were collected. Samples concentrated by formol–ether method (FEM) and Mini Parasep® SF foecal concentrator and unconcentrated samples were subjected to wet mount, iodine mount microscopy and smear examination by modified acid-fast staining. Results: Direct wet mount detected 72 positive samples (48.6%), whereas 77 (51.3%) and 80 (53.3%) samples were detected by FEM and Mini Parasep® SF methods, respectively. The sensitivity of detection of parasites was 98.7%, 95% and 90.1% with Mini Parasep®, FEM and direct microscopy, respectively. A clearer background with less foecal debris and a better yield of Hymenolepis nana, Trichuris trichiura, Entamoeba coli and Giardia lamblia were noted with Mini Parasep®. Conclusion: Mini Parasep® SF technique is simple, rapid and less cumbersome than conventional diagnostics, making it suitable for routine use. In addition, it offers higher sensitivity and better background clearance than both direct stool examination and FEM.
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Hepatitis B virus X protein: The X factor in chronic hepatitis B virus disease progression p. 387
Monika Mani, Shanthi Vijayaraghavan, Gopalsamy Sarangan, Ramya Barani, Priya Abraham, Padma Srikanth
DOI:10.4103/ijmm.IJMM_19_421  PMID:32003338
Introduction: Hepatitis B virus (HBV) is the most common aetiological factor causing hepatocellular carcinoma (HCC). HBx gene plays an enigmatic role in HBV-related HCC. In this study we have analysed amino acid substitutions in HBx from HBV-infected individuals of different clinical stages. Materials and Methods: HBV-infected individuals (n = 93) were recruited in the study. DNA was extracted from plasma, amplified, and DNA sequencing was performed using specific primers targeting HBx gene (540 bp). Results: Among the study participants, 57% had chronic HBV infection, 30% had chronic liver disease (CLD) and 13% had HBV related HCC. Genotypes such as D1, D2, D3, A1, C2 and B2 were identified of which genotype D2 was predominant (78%). HBxC-terminal deletion was observed in four hepatitis B e antigen (HBeAg) negative participants with CLD. The frequency of aminoacid substitution in proapoptotic domain was higher in HBeAg negative participants including I127V (34%), K130M (34%), V131I (40%). The frequency of double mutation (K130M+V131I) and triple mutation (I127V+K130M+V131I) were found to be higher (32% and 36%) in HBeAg negative participants. Also, we identified L5M substitution (4.3%) in HBeAg positive participants with advanced liver disease. Conclusion: In HBx gene, aminoacid substitutions at positions 127, 130, 131 are associated with poor expression of HBeAg. We suggest screening for HBx aminoacid substitutions especially in patients with HBeAg negative chronic HBV infection to predict the clinical outcome and enable early treatment to prevent disease progression.
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Emergence of dengue virus 4 as the predominant serotype during the outbreak of 2017 in South India p. 393
P Ferdinamarie Sharmila, K Vanathy, Barathidasan Rajamani, Venkatesh Kaliaperumal, Rahul Dhodapkar
DOI:10.4103/ijmm.IJMM_19_338  PMID:32003339
Context: Dengue virus (DENV) causes acute febrile illness in tropical and subtropical countries. In India there is a steady increase in incidence since 1950s which could be attributed to emergence of new serotype or lineage\clade shifts in circulating DENV. Aims: We aimed to perform molecular characterisation and phylogenetic analysis on samples from the recent outbreak (August–October 2017). Settings and Design: Retrospective epidemiological analysis of dengue outbreak. Subjects and Methods: Samples positive for non-steroidal 1 antigen by enzyme-linked immunosorbent assay (n = 147) were included. The study was approved by our institute ethics committee (JIP/IEC/2018/496). Five hundred and eleven base pair of capsid and pre-membrane encoding genes (CprM) region was amplified using Lanciotti primers, followed by second round of polymerase chain reaction using serotype specific primers. Samples which were positive by second round (n = 68) were sequenced and genotyped using Basic Local Alignment Search Tool analysis and phylogenetic tree was constructed by MEGA7 software. Results: Phylogenetic analysis of CprM sequences identified all 4 serotypes in circulation during this outbreak. We observed both single (n = 50) and concurrent infections (n = 18), with DENV4 as the major contributor (64%). Within Genotype I of DENV4 we observed a distinct new clade (Clade E) which was 2.6% ± 0.9%–5.5% ± 1.1% divergent from the other clades. Among the concurrent infection, DENV 4 and DENV 2 combination was observed to form the majority (77.8%). Conclusions: Overall this study documents the emergence of DENV4 as the major serotype in circulation, replacing DENV1, 2 and 3 which had been previously reported from Tamil Nadu and Puducherry. This substantiates the need for continuous monitoring in endemic countries like India, where such data may impact the formulation of vaccine policy for dengue.
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Dynamics of the occurrence of influenza in relation to seasonal variation in Chennai, Tamil Nadu: A 7 -year cumulative study p. 401
Ramesh Kiruba, BV Suresh Babu, AK Sheriff, P Gunasekaran, CP Anupama, N Saran, V Senthil Kumar, P Padmapriya, N Nivas Chakravarthy, Krishnasamy Kaveri
DOI:10.4103/ijmm.IJMM_19_226  PMID:32003340
Background: Influenza viruses have emerged as virulent pathogens causing considerable burden across the world. A thorough understanding of the pattern in occurrence of influenza globally is the need of hour. The present study deals with analysis of the dynamics of Influenza virus, especially the influence of seasonal change on viral circulation and causation of epidemics/pandemics in the context of subtropical region. Methods: During the 7 year (2009–2015) study, 36670 specimens were subjected to influenza analysis. Nasopharyngeal swabs collected from suspected patients from Chennai, Tamil Nadu, were tested and typed by real-time polymerase chain reaction assay. Results: During 2009 pandemic, among influenza A positives 95.16% were Apdm09, indicating that there was a predominant circulation of Apdm09. During postpandemic period, there were waves in the occurrence of Apdm09 which indicates fall in immunity with buildup in the susceptible population. Conclusion: In Chennai, Tamil Nadu, influenza positivity started with the onset of monsoon and peaks during the postmonsoon months throughout the study period. The assessment of meteorological factors compounding influenza activity can help in raising alerts to the public health officials of impending disaster which suggests that Influenza vaccination can be initiated before monsoon months in South India.
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VP1-binding protein glucose-regulated protein 78 as an important mediator for enterovirus 71 infecting human brain microvascular endothelial cells p. 406
Wenying Luo, Peng Liang, Santhosh Puthiyakunnon, Lawei Yang, Cao Hong
DOI:10.4103/ijmm.IJMM_19_194  PMID:32003341
Purpose: Enterovirus 71 (EV71) is one of the main pathogens causing hand, foot and mouth disease, which could even induce severe brain damage in some patients. As the underlying mechanism of the invasion and replication process still remains largely unknown, we investigated the role of candidate proteins expressed during EV71 invasion in human brain microvascular endothelial cells (HBMECs) to delineate the pathophysiological mechanism of EV-71 infection. Materials and Methods: Ninety-one candidate EV71-associated proteins which could bind the major capsid protein (viral protein 1 [VP1]) of EV71 on the HBMEC were identified by applying an analysis of glutathione-S-transferase pull-down coupling with liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS). Seventy-eight kDa glucose-regulated protein 78 (GRP78) binding to the VP1 protein was further validated by co-immunoprecipitation, immunofluorescence and western blot analysis. To explore the role of GRP78 in EV71 infection, GRP78 was knocked down and overexpressed in HBMEC and was verified by TCID50 assay. Results: LC-ESI-MS/MS-identified 91 proteins were subjected to gene ontology analysis, and on molecular and biological function analysis revealed GRP78 act as an important binding protein in mediating EV71 infection. In addition, immunofluorescence demonstrated the co-localisation of GRP78 and VP1 in cytoplasm of the infected HBMEC. The TCID50 assay showed that knockdown of GRP78 could attenuate the replication capacity of EV71 in HBMEC, and the overexpression could increase the virus titre in HBEMC at 24 h post-infection suggesting that GRP78 was associated with the replication capacity of EV71 in HBMEC. Conclusion: These findings provided evidence that GRP78 plays an important role during the progression of EV71 infection as a mediator in HBMEC.
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Occurrence of viral gastroenteritis in children below 5 years: A hospital-based study from Assam, India p. 415
Shalini Goldar, Gitika Rajbongshi, Kailash Chamuah, Syed Tanwir Alam, Ajanta Sharma
DOI:10.4103/ijmm.IJMM_19_79  PMID:32003342
Viral gastroenteritis is an important cause of mortality and morbidity in children under 5 years of age. Many a time, these cases go unnoticed causing immense scarcity of data on viral diarrhoea. The study aimed to determine the occurrence of viral gastroenteritis among children below 5 years and the aetiological viral agents. Stool samples were collected from patients suffering from acute gastroenteritis. Real-time polymerase chain reaction was done for detection of rotavirus, adenovirus, norovirus, astrovirus and sapovirus. Viruses were detected in 55% of children. Adenovirus was found to be the most common virus (33.7%), followed by rotavirus infection (28.7%).
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Diverse aminoglycoside phosphotransferase types conferring aminoglycoside resistance in Enterobacteriaceae: A single-centre study from Northeast India p. 418
Jayalaxmi Wangkheimayum, Mohana Bhattacharjee, Bhaskar Jyoti Das, K Melson Singha, Debadatta Dhar Chanda, Debadatta Dhar Chanda, Deepshikha Bhowmik, Amitabha Bhattacharjee
DOI:10.4103/ijmm.IJMM_19_262  PMID:32003343
The present study investigates the molecular basis of aph-mediated aminoglycoside resistance and their transmission dynamics in a tertiary care hospital of Northeast India. Two hundred forty one isolates (230 Escherichia coli and 11 Klebsiella pneumoniae) were collected and screened for aminoglycoside resistance genes. Various aph types were amplified using polymerase chain reaction (PCR) assay. Plasmid incompatibilty, horizontal transferability and ERIC-PCR based typing were carried out for all the positive isolates. Among them, 67 isolates showed the presence of aph gene. Aph (3“)-IIIa and aph (3')-Via were predominant and horizontally transferable. All the plasmids were of incompatibility I1 group. Twenty-eight different haplotypes of E. coli were found harbouring aph gene types. This study was able to identify diverse aph types in a single centre and their corresponding phenotypic trait.
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Insights to the diphtheria toxin encoding prophages amongst clinical isolates of Corynebacterium diphtheriae from India p. 423
Dhiviya Prabaa Muthuirulandi Sethuvel, Nithya Subramanian, Agila Kumari Pragasam, Francis Yesurajan Inbanathan, Prashant Gupta, Jaichand Johnson, Naresh Chand Sharma, Nanda Hemvani, Balaji Veeraraghavan, Shalini Anandan, Lucky Sangal
DOI:10.4103/ijmm.IJMM_19_469  PMID:32003344
Diphtheria is a dreadful disease caused by Corynebacterium diphtheriae. Lysogenised bacteriophages carrying toxin gene in C. diphtheriae can make the strain toxigenic. However, such phage disseminates the toxin genes to other strains when it undergoes lytic phase. As little is known about the phage diversity in C. diphtheriae in India, the present study was undertaken to investigate the prophages integrated into the genome of 29 clinical isolates of C. diphtheriae using whole-genome shotgun sequencing. Amongst these isolates, 27 were toxigenic, while 2 were non-toxigenic strains. Of the 27 toxigenic strains, all harbored known phages carrying toxin gene and two other phages with unknown function. However, the two non-toxin strains did not harbour any of the phages in the genome. It is imperative to devise prevention strategies that hinder the dissemination of toxin by prophages, as it may increase the complications of diphtheria post-immunisation.
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Seroprevalence of brucellosis in Western Rajasthan: A study from a tertiary care centre p. 426
Yashik Bansal, Alisha Aggarwal, Ravisekhar Gadepalli, Vijaya Lakshmi Nag
DOI:10.4103/ijmm.IJMM_19_358  PMID:32003345
Brucellosis is a significant bacterial zoonotic disease with a high seroprevalence in low-to-middle-income countries where there is a significant contact of humans with animals. This prospective study was conducted to observe the seroprevalence of brucellosis in 75 symptomatic patients with pyrexia of unknown origin (PUO) and 75 high-risk individuals (10 veterinarians, 15 milkmen and 50 healthy contacts of symptomatic patients) with possible exposure to brucellosis. Serum samples collected from these patients and individuals were subjected to rose Bengal test (RBT) and ELISA for the detection of IgM and IgG antibodies. RBT was positive in 50 samples (40 PUO and 10 high risk), of which 25 (33.3%) PUO cases had detectable IgM antibodies, whereas IgG antibodies were detected in 20 patients. None of samples from high-risk individuals was reactive for IgM/IgG antibodies by ELISA. The overall seroprevalence in this study was 16.7% (33.3% in PUO patients). Being a predominantly livestock rearing area, brucellosis is a significant health-care problem in this part of India with this entity being linked to 33% of PUO cases.
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Melioidosis in Odisha: A clinico-microbiological and epidemiological description of culture-confirmed cases over a 2-year period p. 430
Bijayini Behera, Srujana Mohanty, Ashoka Mahapatra, Vinay Kumar Hallur, Baijayantimala Mishra, Anupam Dey, Rajesh Kumar, Tushar K Mishra, Prakash K Sasmal, Mithilesh Sinha, Prasanta R Mohapatra, Manoj K Panigrahi, C Preetam, Rashmi Ranjan Das
DOI:10.4103/ijmm.IJMM_19_367  PMID:32003346
Melioidosis is an emerging infectious disease in India mostly reported from South-western coastal Karnataka and North-eastern Tamil Nadu. We speculate the existence of another major hidden focus in Odisha, one of the eastern coastal states. The clinico-epidemiological features of 47 culture-confirmed melioidosis at a tertiary care teaching hospital over a period of 2 years are reported. Septicaemia was the most common clinical presentation. Diabetes mellitus (DM) was present in 72.3% of our cases. The geo-climatic conditions of Odisha and other coastal states of India and the rise in the incidence of DM demand a nationwide surveillance of melioidosis and creation of melioidosis registry.
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Utility of QuantiFERON®-TB gold In-Tube test compared with tuberculin skin test in diagnosing tuberculosis in Indian children with malnutrition p. 433
Deepthi Boddu, Valsan Philip Verghese, Joy Sarojini Michael, Anila Chacko, Visali Jeyaseelan
DOI:10.4103/ijmm.IJMM_19_227  PMID:32003347
This prospective cohort study was conducted to compare the accuracy of QuantiFERON®-TB (QFT) Gold In-Tube test and tuberculin skin test (TST) in diagnosing tuberculosis (TB) in predominantly bacille Calmette–Guerin-vaccinated children with a high incidence of malnutrition. The sensitivity of the QFT versus the TST was 69.6% versus 52.9% for WHO-defined TB, with specificity of 86% versus 78.3%, respectively. The concordance of the TST and QFT was 79% overall (κ = 0.430), 62.5% in those with WHO-defined TB and 85.7% in those without TB. Majority of the QFT+/TST − discordance was seen in children with TB, whereas majority of the TST+/QFT − discordance was seen in those without TB. The TST was more likely to be negative in children with moderate-to-severe malnutrition (P = 0.003) compared to the QFT, which was more likely to be positive in younger children. The significantly better performance of the QFT in malnourished children and those at younger ages supports its use for TB diagnosis in these subpopulations.
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Phylogenetic diversity of Orientia tsutsugamushi isolates in patients with scrub typhus in Bengaluru, India p. 438
Sneha K Chunchanur, Shwetha J Venugopal, R Ambica, B Dakshayani
DOI:10.4103/ijmm.IJMM_19_267  PMID:32003348
Scrub typhus has re-emerged as an important cause of acute febrile illness in India. There is a dearth of information on strain diversity of Orientia tsutsugamushi from Karnataka, India, hence the present study sought to address this issue. One hundred clinically suspected cases of scrub typhus/rickettsiosis (as per the DHR-ICMR guidelines) were included. Nested-polymerase chain reaction (PCR) for 56-kDa gene and phylogenetic analysis was performed. PCR was positive in 22 cases and phylogenetic analysis showed the presence of different strains, with predominance of clustering (57%) with Gilliam-type for the first time in Karnataka. Knowledge of genetic diversity has implications in development of diagnostics and vaccine.
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Determination of Biofilm-Forming Capacity of Otopathogens Isolated from Discharging Ears in Children with Chronic Otitis Media p. 442
Zoremsangi Ralte, P Naina, Anushree Amladi, Mary John, Shalini Anndan, Ajoy Mathew Varghese
DOI:10.4103/ijmm.IJMM_19_404  PMID:32003349
Chronic otitis media is a common disease of the developing world with persistent ear discharge, leading to major complications. This study describes the microorganisms isolated from the middle ear and nasopharynx of children with chronically discharging ears. Middle ear and nasopharyngeal swabs from 89 children were studied, and the microorganisms isolated were assessed for biofilm-forming ability. Methicillin-susceptible Staphylococcus aureus was common in the nasopharynx, while the middle ear showed predominantly pseudomonas and Methicillin-resistant S. aureus. Pseudomonas aeruginosa showed strong biofilm formation, whereas Escherichia coli, Proteus sp. and Providentia sp. were weak biofilm producers. S. aureus isolates were negative for biofilm formation.
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Group B Streptococcus vaginal colonisation in pregnant women at a tertiary care hospital in Mumbai p. 446
Shalmali Deshpande, Tanu Singhal, Suchitra N Pandit, Sweta Shah
DOI:10.4103/ijmm.IJMM_19_448  PMID:32003350
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Utility of Xpert® MTB/RIF in the diagnosis of extrapulmonary tuberculosis p. 448
Vidya Krishna, Ram Gopalakrishnan, Anil Tarigopula, Senthur Nambi Panchatcharam, Suresh Kumar Dorairajan, Ramasubramanian Venkatasubramanian
DOI:10.4103/ijmm.IJMM_19_149  PMID:32003351
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CASE REPORTS Top

Paradoxical upgradation response in non-HIV tuberculosis: Report of two cases p. 450
Meghana Nathani Kabra, Thrinadh Kunapareddy
DOI:10.4103/ijmm.IJMM_18_242  PMID:32003352
A paradoxical upgradation response in tuberculosis (TB) is defined as the worsening of a pre-existing tubercular lesion or the appearance of a new lesion in a patient whose clinical symptoms initially improved with anti-TB treatment. A paradoxical response is common in HIV patients in the form of immune reconstitution inflammatory syndrome. A similar kind of response can also be seen in immunocompetent patients. Here, we present two cases of non-HIV TB who initially improved with antitubercular therapy (ATT) but worsened thereafter. After excluding possibilities such as multidrug-resistant TB, treatment failure or a superadded infection, a paradoxical upgradation response was diagnosed. Both the cases improved after treatment with corticosteroids in addition to ATT.
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Fungal infection in a post-renal transplant patient with Diaporthe p. 454
K Vichitra, Lokeshwari Gopal, Balajee Govindarao, V Chandrasekaran, Anupma Jyoti Kindo
DOI:10.4103/ijmm.IJMM_19_96  PMID:32003353
Post-renal transplant fungal infections continue to be a major cause of mortality and morbidity. Universally reported fungi are Candida, especially Candida albicans, Cryptococcus, Aspergillus, Trichophyton rubrum and Pityriasis versicolor. Here, we report a case of infection caused by a rare fungus Diaporthe. It is an endophyte reported as plant pathogens and infrequently in humans and mammals. The patient was a renal transplant recipient on immunosuppressant. He had hypothyroidism and diagnosed with permanent pacemaker due to a complete heart block. The patient was treated with itraconazole (200 mg) successfully.
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ERRATUM Top

Erratum: Abstracts - Indian journal of medical microbiology - supplement 1 - 2019 - Volume 37 p. 457

DOI:10.4103/0255-0857.277076  PMID:32003354
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2004 - Indian Journal of Medical Microbiology
Published by Wolters Kluwer - Medknow

Online since April 2001, new site since 1st August '04