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   Table of Contents - Current issue
Coverpage
November 2019
Volume 150 | Issue 5
Page Nos. 425-514

Online since Monday, January 6, 2020

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EDITORIAL  

Diabetes mellitus, vitamin D & osteoporosis: Insights Highly accessed article p. 425
Ravinder Goswami, Abilash Nair
DOI:10.4103/ijmr.IJMR_1920_19  
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COMMENTARY Top

Diagnosis & management of infections due to non-tuberculous mycobacteria in developing countries: Looking ahead p. 429
VM Katoch
DOI:10.4103/ijmr.IJMR_2096_19  
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VIEWPOINT Top

Waterborne & foodborne viral hepatitis: A public health perspective p. 432
Abhik Sinha, Shanta Dutta
DOI:10.4103/ijmr.IJMR_1430_18  
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REVIEW ARTICLES Top

Typhoid fever: Control & challenges in India p. 437
Bratati Mukhopadhyay, Dipika Sur, Sanjukta Sen Gupta, NK Ganguly
DOI:10.4103/ijmr.IJMR_411_18  
Enteric fever is a common but serious disease that affects mostly children and adolescents in the developing countries. Salmonella enterica serovar Typhi remains responsible for most of the disease episodes; however, S. Paratyphi A has also been reported as an emerging infectious agent of concern. The control measures for the disease must encompass early diagnosis, surveillance and vaccine to protect against the disease. Sanitation and hygiene play a major role in reducing the burden of enteric diseases as well. The current status of diagnostics, the surveillance practices in the recent past and the vaccine development efforts have been taken into account for suggesting effective prevention and control measures. However, the challenges in all these aspects persist and cause hindrance in the implementation of the available tools. Hence, an integrative approach and a comprehensive policy framework are required to be in place for the prevention, control and elimination of typhoid fevers.
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Microbiological diagnosis of tuberculous meningitis: Phenotype to genotype p. 448
Ravindra Kumar Garg
DOI:10.4103/ijmr.IJMR_1145_19  
Tuberculous meningitis (TBM) is a commonly encountered central nervous system infection. Characteristic clinical, imaging and cerebrospinal fluid parameters help clinicians to make a prompt presumptive diagnosis that enables them to start empirical anti-tuberculosis treatment. There are several close mimic to TBM, such as partially treated pyogenic meningitis, fungal meningitis, sarcoidosis, meningeal metastases and meningeal lymphomatosis. Microbiological confirmation instils a sense of confidence amongst treating physicians. With conventional phenotypic methods (cerebrospinal fluid microscopy and culture), in more than 50 per cent patients, microbiological confirmation is not achieved. Moreover, these methods take a long time before providing conclusive results. Negative result does not rule out Mycobacterium tuberculosis infection of the brain. Genotypic methods, such as IS 6110 polymerase chain reaction and automated Xpert M. tuberculosis/rifampicin (MTB/RIF) assay system improved the TBM diagnostics, as results are rapidly available. Xpert MTB/RIF assay, in addition, detects rifampicin resistance. Xpert MTB/RIF Ultra is advanced technology which has higher (60-70%) sensitivity and is being considered a game-changer in the diagnostics of TBM. A large number of TBM cases remain unconfirmed. The situation of TBM diagnostics will remain grim, if low-cost technologies are not widely available. Till then, physicians continue to rely on their clinical acumen to start empirical anti-tuberculosis treatment.
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ORIGINAL ARTICLES Top

A prospective study of non-tuberculous mycobacterial disease among tuberculosis suspects at a tertiary care centre in north India p. 458
Surendra Kumar Sharma, Rohini Sharma, Binit Kumar Singh, Vishwanath Upadhyay, Indra Mani, Madhavi Tripathi, Prahlad Kumar
DOI:10.4103/ijmr.IJMR_194_19  
Background & objectives: The burden of non-tuberculous mycobacterial (NTM) disease is increasing worldwide. The disease shares clinicoradiological features with tuberculosis (TB), Nocardia and several fungal diseases, and its diagnosis is frequently delayed. The present study was performed to determine the frequency of NTM disease among TB suspects in a tertiary care centre in north India. Methods: In this prospective study, mycobacterial culture isolates from pulmonary and extrapulmonary specimens among TB suspects were tested with immunochromatographic assay (ICA). All ICA-negative isolates were considered as NTM suspects and further subjected to 16S-23S rRNA internal transcribed spacer gene sequencing for confirmation and species identification. Patients with active disease were treated with drug regimen as per the identified NTM species. Follow up of patients was done to determine clinical, radiological and microbiological outcomes. Results: Of the 5409 TB suspects, 42 (0.77%) were diagnosed with NTM disease. Patients with active disease consenting for treatment were treated and followed up. Thirty four patients had NTM pulmonary disease (NTM-PD) and the remaining eight had extrapulmonary NTM (EP-NTM) disease. Mycobacterium intracellulare and M. abscessus, respectively, were most frequently isolated from NTM-PD and EP-NTM patients. Fifteen NTM-PD and seven EP-NTM patients successfully completed the treatment. Ten patients died due to unrelated causes, five were lost to follow up and another four declined the treatment. Interpretation & conclusions: Our study showed that the frequency of NTM disease was low among TB suspects at a large tertiary care centre in north India and this finding was similar to other Indian studies. More studies need to be done in other parts of the country to know the geographical variation in NTM disease, if any.
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Frequent plateletpheresis donations & its effect on haematological parameters: An observational study p. 468
Sweta Nayak, Poonam Coshic, RM Pandey, Kabita Chatterjee
DOI:10.4103/ijmr.IJMR_512_18  
Background & objectives: The well-being of donors undergoing frequent plateletpheresis has been a matter of concern. The aim of this study was to analyze the effect of frequent plateletpheresis on the haematological parameters (HP) of repeat donors. Methods: The study was conducted during February 2016 to March 2017 on all the repeat plateletpheresis donors undergoing the 2nd plateletpheresis within a month of the first in a tertiary care centre. Donors repeating plateletpheresis 3rd and 4th times were also studied. The values of the HP observed on follow up after plateletpheresis done on three different separators were compared. Results: HPs of the 98 donors were similar at follow up except mean platelet volume (P <0.05). Of the 98 donors, 35 were followed up within a week and 63 were followed up within 8-30 days. No significant alteration was found in the HPs except a significant difference in the variation of platelet counts of the two groups (P=0.025). In 34 donors who presented 3rd time for plateletpheresis (mean gap between 1st and 3rd plateletpheresis=31 days), no significant differences in the HPs were found except the platelet distribution width (P <0.05). Minimal difference in the HP was found in the baseline and the follow up of 3rd plateletpheresis i.e., at 4th plateletpheresis donation. Plateletpheresis through all the three cell separators used had similar effects on the follow up HPs. Interpretation & conclusions: Repeated plateletpheresis can be done without any detrimental effects on the cell counts of the plateletpheresis donors. The three cell separators yielded similar post-donation follow up haematological parameters.
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Is it necessary to focus on morphologically normal acrosome of sperm during intracytoplasmic sperm injection? p. 477
Ziba Zahiri, Fatemeh Ghasemian
DOI:10.4103/ijmr.IJMR_866_18  
Background & objectives: The detailed assessment of sperm morphology is important in the semen of infertile men because there is a low proportion of normal spermatozoa. One of the parameters of such sperm morphology is the acrosome, and its effect on assisted reproductive outcomes is controversial. This study was undertaken to evaluate the association between different forms of acrosome on the chromatin status and the assisted reproductive outcomes. Methods: A total of 1587 unstained sperms from 514 infertile men were captured and analyzed for different acrosome forms (normal, large, small, skew, amorphous acrosome and without acrosome) in real time during intracytoplasmic sperm injection into oocytes. The association between the percentage of sperms with atypical acrosome and head shapes and the sperm chromatin status was studied. Fertilization, zygote and embryo quality and clinical pregnancy rates were calculated for different groups of sperms. Results: The highest frequency of irregular shapes of acrosomes, such as small, large and amorphous, was observed in abnormal ellipticity, anteroposterior symmetry and angularity parameters, respectively (P <0.05). The fertilization rate of injected sperms with large (P <0.01) and small (P=0.001) acrosomes and without acrosome (P=0.001) was significantly lower in comparison with normal acrosomes. The quality of zygotes (Z3, P=0.05), embryos (grade C, P <0.05) and the pregnancy rate (P=0.001) from injected sperms with large acrosomes were significantly lower compared with normal acrosomes. Interpretation & conclusions: Our findings showed that the different sperm acrosome morphologies (e.g., large, small, and without acrosome) might negatively relate with chromatin integrity and decrease the sperm's fertility potential and pregnancy rate during intracytoplasmic sperm injection (ICSI) cycles.
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Assessing the susceptibility of highly pathogenic avian influenza H5N1 viruses to oseltamivir using embryonated chicken eggs p. 486
Deeksha S Tare, Sadhana S Kode, Aeron C Hurt, Shailesh D Pawar
DOI:10.4103/ijmr.IJMR_845_18  
Background & objectives: The susceptibility of influenza viruses to neuraminidase inhibitors (NAIs) is studied using enzyme-based assays, sequence analysis and in vitro and in vivo studies. Oseltamivir carboxylate (OC) is the active prodrug of the NAI oseltamivir. There is lack of information on the use of embryonated chicken eggs for studying susceptibility of highly pathogenic avian influenza (HPAI) H5N1 viruses to antiviral drugs. The aim of the present study was to assess the use of 10 day old embryonated chicken eggs for studying antiviral susceptibility of HPAI H5N1 viruses. Methods: Two HPAI H5N1 viruses isolated from India were used in the study. Fluorescence-based NAI assay was performed to determine antiviral susceptibility of these viruses. In ovo antiviral assays were carried out using 10 day old embryonated chicken eggs. The virus dilutions were incubated with 14 μg/ml of OC and inoculated in the allantoic cavity. In the eggs, 50 per cent egg infectious dose (EID50) titres as well as mortality were quantitated. Results: The two viruses used were susceptible to OC in the NAI assay. It was found that there was a significant drop in EID50titres; however, no significant protection from mortality after OC treatment was observed. Interpretation & conclusions: By measuring viral titres, the egg model was suitable to study the susceptibility of HPAI viruses to antiviral drugs along with NAI assay. The present study highlights the use of eggs as a model to study susceptibility of HPAI viruses to OC.
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Outbreaks of dengue in Central India in 2016: Clinical, laboratory & epidemiological study p. 492
Shraddha Tiwari, Mohan K Shukla, Gyan Chand, Lalit Sahare, Mahendra J Ukey, Piyush Joshi, Rameshwar Khedekar, Neeru Singh, Pradip V Barde
DOI:10.4103/ijmr.IJMR_1315_18  
Background & objectives: Dengue virus (DENV) causes outbreaks and sporadic cases in tropical and subtropical countries. Documenting intricacies of DEN outbreaks is important for future interventions. The objective of this study was to report clinical, laboratory and epidemiological features of DEN outbreaks reported in different districts of Central India in 2016. Methods: In 2016, outbreaks (n=4) suspected of DEN were investigated by rapid response team. Door-to-door fever and entomological surveys were conducted. Blood samples were collected and tested using NS1 or IgM ELISA; real-time reverse transcription-polymerase chain reaction was done to identify serotypes of DEN virus (DENV). NS1-positive samples were tested for the presence of IgG by ELISA. Clinical and demographic data were collected and analyzed. Results: Outbreaks occurred in both urban and rural areas in monsoon season and Aedes aegypti was identified as the vector. Fever, chills, headache and myalgia were the major symptoms; no fatality was recorded. Of the 268 DEN suspects, 135 (50.4%) were found serologically positive. DEN positivity was higher (n=75; 55.56%) among males and in the age group of 16-45 yr (n=78; 57.8%). DENV 3 followed by DENV 2 were detected as the major responsible serotypes. High attack rates (up to 38/1000) and low cumulative IgG prevalence (14.9%) were recorded in rural areas. Interpretation & conclusions: Our study showed that DENV 3 was the major serotype responsible for outbreaks that occurred in monsoon. High attack rates and lower number of secondary infections in rural areas indicated that DENV is emerging in rural parts of Central India. Early diagnosis at local level and timely intervention by mosquito control activities are needed to avoid such outbreaks in future.
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Japanese encephalitis virus-induced neuropathology in mouse model infected through the conjunctival route p. 498
Menaka Sethi, Tareni Das, Neelam Tomar, Jeny K John, Zunjar B Dubal, Kaushal K Rajak, Rajendra Singh, G Saikumar
DOI:10.4103/ijmr.IJMR_2078_17  
Background & objectives: Mouse is a preferred animal model for studying pathogenesis of Japanese encephalitis virus (JEV) infections, and different routes of inoculation have been tried. Some neurotropic viruses can reach the brain following infection through ocular route. This study was undertaken to establish JEV-induced clinical disease in mouse model through conjunctival route and document the neuropathological effects. Methods: Ten two-week old Swiss albino mice were inoculated with 5 μl Vero cell cultured virus containing 104.7 TCID50 JEV through conjunctival route. Clinical signs of mice were observed twice daily. After necropsy examination, different organs including eyes and olfactory bulbs were collected for histopathological examination, quantification of viral copy number and antigen by real-time TaqMan assay and immunohistochemistry, respectively. Results: Infected mice showed characteristic clinical signs of JE by 4 days post-infection (dpi). Histopathological lesions in brain included perivascular cuffing by mononuclear cells, focal gliosis, necrosis of neurons and neuronophagia and astrocytosis in the cerebrum, cerebellum and the brainstem. JEV viral load was highest in the brain followed by intestine, heart, liver, spleen, lung and kidney. JEV antigen was detected in the bipolar and ganglion cells of the retina and in the mitral cells and periglomerular cells of olfactory bulb and other parts of the brain. Interpretation & conclusions: JEV infection in mice through conjunctival route produced characteristic clinical signs of the disease and neuropathological lesions. Demonstration of JEV antigen in association with neuropathological lesions in the central nervous system and neuronal cells of the eye showed that conjunctival route could be an effective alternate route for virus invasion into the brain. These findings have biosafety implications for researchers, veterinary practitioners and pig farmers.
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Effect of different methods of pasteurization on bactericidal action of human milk: A prospective observational study p. 504
Savita Patil, Anitha Ananthan, Ruchi Nimish Nanavati, Gita Nataraj, Priyanka Prasad
DOI:10.4103/ijmr.IJMR_600_18  
Background & objectives: Pasteurization involves not only inactivation of pathogens, but also loss of immunological functions and bactericidal action of human milk. Hence, this study was aimed to explore the stability of such bactericidal action after subjecting human milk samples to thermal pasteurization under different condition of time and temperature. Methods: In this observational study 48 human milk samples were analyzed over a period of three months. The effect of holder and flash methods of pasteurization on bactericidal action against Escherichia coli was evaluated compared to the control sample before and after 72 h of storage at −18°C. Results: Both holder and flash methods of pasteurization showed significant reduction in the E. coli growth to 46.4 and 25.5 per cent, respectively, after 24 h of incubation (P <0.001). The bactericidal activity was significantly more in samples subjected to holder method compared to flash method before and after 72 h of storage (46.41±15.38 vs. 25.50±30.74, P <0.001 and 42.27±20.38 vs. 18.33±28.55, P <0.001). Interpretation & conclusions: Our results showed that the bactericidal activity of human milk was better preserved by the holder method of pasteurization. Further well-powered and well-designed randomized trials are needed to confirm the findings.
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Status of adult immunity to hepatitis A virus in healthcare workers from a tertiary care hospital in north India p. 508
Sanshriti Chauhan, Jyotsna Agarwal, Amita Jain, KK Sawlani, Prashant Gupta, Abhishek Goel, Neera Verma, D Himanshu
DOI:10.4103/ijmr.IJMR_787_18  
Background & objectives: Humans are considered to be the principal host for hepatitis A virus (HAV) infection. In India, heterogeneous groups of susceptible individuals coexist in different regions. There has been a decline in antibody titres to HAV among young adults which may pose a major public health problem. The objective of this study was to assess the IgG anti-HAV level among healthcare workers (HCWs) in the age group of 20-60 yr and its association with the socio-demographic variables. Methods: Blood sample (2 ml) was collected under aseptic conditions from each participant followed by the preparation of serum and storing at −20°C. ELISA-based kits were used for the determination of IgG antibodies to HAV in the human serum samples. Results: Two hundred and fifty four HCWs were enrolled. IgG anti-HAV antibodies were detected in 97.2 per cent of the samples analyzed. No differences were observed in the levels of IgG anti-HAV antibody and education, income, occupation and socio-economic classes of the HCWs. A seropositivity rate of over 90 per cent was seen amongst all the socio-economic classes. Interpretation & conclusions: High levels of IgG protective antibodies were seen among the studied HCWs, hence HAV vaccination may not be required. It will be advisable to do a cost-benefit analysis of vaccination for HAV.
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CLINICAL IMAGE Top

Pancreatico-pleural fistula: An unusual cause of chronic cough p. 512
Anand V Kulkarni, Murali. S Shasthry
DOI:10.4103/ijmr.IJMR_1674_18  
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BOOK REVIEW Top

Vaccines for cancer immunotherapy: An evidence-based review on current status and future perspectives p. 514
Mausumi Bharadwaj
DOI:10.4103/ijmr.IJMR_1275_19  
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