BACKGROUND AND OBJECTIVES To determine the real-world data regarding the use of Rituximab (RTX) i... more BACKGROUND AND OBJECTIVES To determine the real-world data regarding the use of Rituximab (RTX) in neuroinflammatory disorders (NIDS) and assess the outcomes following RTX treatment. METHODS A cohort of consecutive patients with NIDS started on RTX (2018-2020) was included. The outcomes assessed were the proportion with favourable clinical response (FCR) as defined by clinical remission/ improvement using disease specific disability scores, comparative efficacy based on timing of initiation and B cell kinetics. RESULTS A total of 97 patients with NIDS were included. The mean age was 36.43 (±14.4) years and median duration of follow - up being 15 months (IQR 12-16). Forty patients (41.2%) were initiated on RTX "early" in disease course. Favourable clinical response at last follow-up was seen in 94.9% (n = 92). The mean change in disability score (mRS) was 1.89 (SD 1.30) (p < 0.001). RTX appeared more effective when initiated "early" with higher remission rates (75% vs. 42%, p 0.015). B cell kinetics varied across NIDS, with 73% having adequate depletion at 6 months. Minor adverse events including infusion related reactions were reported in 9%. CONCLUSIONS RTX has a favourable efficacy and safety profile. Future prospective studies are needed to establish the optimal timing of initiation and need for disease-based dosage regimens.
Neuromyelitis optica spectrum disorders (NMOSD) are characterised by pathological antibodies to a... more Neuromyelitis optica spectrum disorders (NMOSD) are characterised by pathological antibodies to aquaporin-4 water channels of astrocytes, resulting in severe brain and spinal cord injury. Serological evidence suggests that Epstein-Barr virus (EBV) reactivation may contribute to their pathogenesis. We describe an unusual case of a woman with fever, rash and headache preceding an Aquaporin-4 antibody positive longitudinally extensive transverse myelitis. EBV was detected in her cerebrospinal fluid by polymerase chain reaction assay. This case highlights the potential role of EBV in the pathogenesis of NMOSD.
We reviewed qualitative and quantitative data from the published medical literature, the Integrat... more We reviewed qualitative and quantitative data from the published medical literature, the Integrated Disease Surveillance Programme (IDSP) of the Ministry of Health and Family Welfare, and the rickettsial infection database at Christian Medical College, Vellore (CMC) to understand the burden of disease across the country. We also conducted a cross-sectional, population-based survey in Vellore district to estimate the seroprevalence of scrub typhus in the community using immunoglobulin (Ig)G and IgM antibodies. We assessed the risk factors for acquiring the disease in the community in a case–control study. We also analysed the severity of disease and current management options among patients admitted to CMC. The study was approved by the Ethics Review Board of CMC.
Two specific serological tests, a Dot enzyme immunoassay (EIA) and an immunoglobulin (Ig)M enzyme... more Two specific serological tests, a Dot enzyme immunoassay (EIA) and an immunoglobulin (Ig)M enzyme-linked immunosorbent assay (ELISA) using the 56 kDa antigen and the Weil-Felix test were evaluated for diagnosis of scrub typhus. Sensitivity of 100, 86.5 and 43.5% were observed with Dot EIA, IgM ELISA and Weil-Felix test, respectively. False-positive reactions were observed in patients with falciparum malaria, pulmonary tuberculosis, S. viridans septicemia and typhoid fever using Dot EIA and IgM ELISA. Therefore, although Dot EIA and IgM ELISA are useful in the serodiagnosis of scrub typhus, efforts should be made to rule out other febrile illnesses.
Background: Peripheral nerve hyperexcitability (PNH) and neuromyotonia have been mainly attribute... more Background: Peripheral nerve hyperexcitability (PNH) and neuromyotonia have been mainly attributed to antibodies against voltage-gated potassium channels (VGKC). Concurrent autoimmune disorders, malignancies, and heavy metal toxicity have also been implicated. There is scarce mention about infection as a triggering factor for PNH. There are no reports of methicillin-resistant Staphylococcus aureus (MRSA) infection being a possible precipitating factor for development of PNH. Methods: Case series and literature review. Results: Four subjects were diagnosed to have features of PNH based on clinical and electrophysiological assessment. All the subjects had concurrent evidence of cutaneous abscesses requiring surgical intervention and antibiotic therapy. The cultures in all of them revealed growth of Staphylococcus aureus with three of them being MRSA isolates. Two subjects tested positive for anti-VGKC antibodies. There was remarkable resolution in neuromyotonia after antibiotics in three subjects. One subject succumbed to fulminant MRSA septicemia. Conclusion: There appears to be a definitive link between staphylococcal infection (MRSA in particular) and development of PNH. The temporal evolution of PNH associated with the infection and resolution following treatment of the infection does support a causal association. The enterotoxins produced by staphylococci act as superantigens and could trigger an inflammatory cascade along with development of cross reacting antibodies against VGKC in peripheral nerves. Future studies with animal models could provide more directions in this regard.
Commercial dengue virus (DENV) nonstructural-1 (NS1) Ag detection immunoassays often perform poor... more Commercial dengue virus (DENV) nonstructural-1 (NS1) Ag detection immunoassays often perform poorly, particularly in secondary DENV infection. To develop a highly sensitive NS1 ELISA, we generated a large repertoire of anti-DENV NS1 mouse mAbs (n = 95) that falls into 36 mAb classes based on binding specificities. The identified mAb pair, capable of efficiently detecting NS1 from four DENV serotypes in an immunoassay, was selected based on multiparametric analysis. The selected mAbs have subnanomolar affinities for NS1 with recognition sites outside the immunodominant wing domain. The assay was converted to an ELISA kit, which showed higher analytical sensitivity (3-fold to 83-fold) for NS1 from four DENV serotypes than commercial Platelia NS1 ELISA (Bio-Rad Laboratories). Compared to RT-PCR, the developed NS1 ELISA showed 78.57% (66 of 84) sensitivity, whereas Platelia NS1 ELISA showed a sensitivity of 60.71% (51 of 84). In a subgroup of RT-PCR–positive secondary dengue samples, ou...
Introduction: Skin colonization is a risk factor for multi-drug resistant (MDR) catheter-associat... more Introduction: Skin colonization is a risk factor for multi-drug resistant (MDR) catheter-associated bloodstream infections (CABSI). This study aimed to determine the prevalence and spectrum of skin colonizing MDR organisms in incident HD patients and their correlation with CABSI. Methods: This single-center prospective cohort study included consecutive adult incident HD patients who underwent tunneled or non-tunneled internal jugular vein HD catheter insertion between June 1, 2017 and October 31, 2017. Nasal, axillary, and exit site swabs were obtained prior to catheter insertion, at 14–21 days, and 28–35 days after catheter insertion. Results: Forty-three patients (69.7% male, 32.5% diabetic) were included and provided baseline swabs, while 29 and 10 patients respectively were available for follow-up swabs. MDR bacterial colonization, MRSA colonization, and MDR gram-negative colonization on the baseline set of swabs were seen in 76.7%, 69.7%, and 9.3% patients respectively. Of the 29 patients with at least two consecutive sets of swabs, 79.3% showed persistent colonization by MDR gram-positive organisms, most commonly by MRSA. Six patients developed a CABSI during the follow-up period (incidence rate 3.7 per 1000 patient days), 83.4% were gram negative, and in only one instance (16.6%) was the bacterial strain identical to that which had previously colonized the skin. Conclusions: Three-fourths of HD patients were colonized by MDR bacteria prior to HD initiation. Despite the majority being persistently colonized by MDR gram-positive organisms, CABSIs were predominantly gram negative.
Detection of Orientia tsutsugamushi DNA in a trombiculid mite chigger species suggests that it mi... more Detection of Orientia tsutsugamushi DNA in a trombiculid mite chigger species suggests that it might be a potential vector of scrub typhus in an endemic area. Over a period of 20 mo, 85 rats were trapped, 57 had chiggers that were identified by standard morphometric techniques. The chigger pools were assessed by performing PCR assays targeting fragments of the single-copy genes 56 kDa type-specific antigen gene (TSA56) by nested PCR and the 47 kDa (htrA) quantitative real-time PCR (qPCR). The novel traD SYBR green assay that detects a multicopy gene was also performed. In total, 27 chigger pools were positive by traD qPCR, of which only 7 were positive by 47 kDa qPCR and in 3 of these, 56 kDa gene was amplified by nested PCR. Orientia tsutsugamushi-specific DNA was detected in Ascoschoengastia spp., Schoengastiella ligula, Leptotrombidium rajasthanense, Leptotrombidium deliense, and Leptotrombidium jayawickremei chigger pools. Therefore, they could be potential vectors of scrub typh...
Spondylodiscitis is an infectious inflammation that affects the intervertebral disc and adjacent ... more Spondylodiscitis is an infectious inflammation that affects the intervertebral disc and adjacent structures. Treating infective spondylodiscitis is often challenging due to the lack of specific symptoms. Here we present an unusual case of infective spondylodiscitis caused by Campylobacter fetus subsp. fetus .
Background:: Antiretroviral therapy (ART) has led to a decline in autoimmune diseases but lacks s... more Background:: Antiretroviral therapy (ART) has led to a decline in autoimmune diseases but lacks studies on its effect on autoantibodies. Methods: It is a cross-sectional study with archived samples from 100 paired HIV-1 infected ART naïve and experienced individuals and 100 prospectively collected matched blood-donor controls. Antinuclear antibody, IgG anticardiolipin antibody, IgM and IgG β2 glycoprotein-1 antibodies, and total IgG levels were detected. Results are expressed as mean with standard deviation (SD), median, percentage positivity, and a p<0.05 is considered significant. The study was approved by the Institutional Review Board. Results: The median viral load of the treatment naïve samples was 4.34 Log copies/mL, while all were virally suppressed post ART with a median duration of treatment for 12 months (range: 3-36 months). The percentage of antinuclear antibody positivity was 5% among ART naïve and controls, with a decrease of 2% post ART (p= 0.441). The positivity ...
Rapid diagnostic test (RDT) kits are widely used in India for the diagnosis of dengue infection. ... more Rapid diagnostic test (RDT) kits are widely used in India for the diagnosis of dengue infection. It is important to evaluate the validity and reliability of these RDTs. The study was aimed to determine the sensitivity, specificity and predictive value of four commercially available RDTs [Panbio Dengue Duo cassette, Standard Diagnostics (SD) Bioline Dengue Duo, J. Mitra Dengue Day-1 test and Reckon Dengue IgG/IgM] against composite reference criteria (CRC), and compare the cost of the tests. In this prospective observational study for diagnostic accuracy, we tested stored blood samples from 132 cases of dengue and 149 controls of other infections as classified based on CRC, with all the four RDTs. The CRC was based on the epidemiological considerations, common clinical features and laboratory abnormalities. The non-dengue controls were the cases of proven alternative diagnosis. The diagnostic performances of the tests were compared in terms of sensitivity, specificity and predictive ...
The immunodominant TSA 56 gene ofOrientia tsutsugamushi, (scrub typhus agent) has four variable r... more The immunodominant TSA 56 gene ofOrientia tsutsugamushi, (scrub typhus agent) has four variable regions (VD-I to VD-IV) making it useful for genotyping. As of date the genotyping data from India is based on partial 56kDa gene sequence analysis. The complete TSA 56 gene sequence is important for knowing the circulating strains and for designing region specific diagnostics and vaccines. This study was undertaken to determineOrientia tsutsugamushigenotypes circulating in and around Vellore using complete and partial TSA 56 gene. Of the 379 whole blood samples from suspected scrub typhus patients, 162 were positive by 47 kDa qPCR. Long protocol to amplify the complete TSA 56 gene (≈1605 bp) was performed on 21 samples. On the same 21 samples the partial gene sequence was also amplified using the Horinouchi (≈650bp) and the Furuya (≈480 bp) protocol. Using a combination of Sanger and Nanopore technology complete sequence was obtained for 9 and near complete (1551 to 1596 bp) for 4 respec...
BACKGROUND AND OBJECTIVES To determine the real-world data regarding the use of Rituximab (RTX) i... more BACKGROUND AND OBJECTIVES To determine the real-world data regarding the use of Rituximab (RTX) in neuroinflammatory disorders (NIDS) and assess the outcomes following RTX treatment. METHODS A cohort of consecutive patients with NIDS started on RTX (2018-2020) was included. The outcomes assessed were the proportion with favourable clinical response (FCR) as defined by clinical remission/ improvement using disease specific disability scores, comparative efficacy based on timing of initiation and B cell kinetics. RESULTS A total of 97 patients with NIDS were included. The mean age was 36.43 (±14.4) years and median duration of follow - up being 15 months (IQR 12-16). Forty patients (41.2%) were initiated on RTX "early" in disease course. Favourable clinical response at last follow-up was seen in 94.9% (n = 92). The mean change in disability score (mRS) was 1.89 (SD 1.30) (p < 0.001). RTX appeared more effective when initiated "early" with higher remission rates (75% vs. 42%, p 0.015). B cell kinetics varied across NIDS, with 73% having adequate depletion at 6 months. Minor adverse events including infusion related reactions were reported in 9%. CONCLUSIONS RTX has a favourable efficacy and safety profile. Future prospective studies are needed to establish the optimal timing of initiation and need for disease-based dosage regimens.
Neuromyelitis optica spectrum disorders (NMOSD) are characterised by pathological antibodies to a... more Neuromyelitis optica spectrum disorders (NMOSD) are characterised by pathological antibodies to aquaporin-4 water channels of astrocytes, resulting in severe brain and spinal cord injury. Serological evidence suggests that Epstein-Barr virus (EBV) reactivation may contribute to their pathogenesis. We describe an unusual case of a woman with fever, rash and headache preceding an Aquaporin-4 antibody positive longitudinally extensive transverse myelitis. EBV was detected in her cerebrospinal fluid by polymerase chain reaction assay. This case highlights the potential role of EBV in the pathogenesis of NMOSD.
We reviewed qualitative and quantitative data from the published medical literature, the Integrat... more We reviewed qualitative and quantitative data from the published medical literature, the Integrated Disease Surveillance Programme (IDSP) of the Ministry of Health and Family Welfare, and the rickettsial infection database at Christian Medical College, Vellore (CMC) to understand the burden of disease across the country. We also conducted a cross-sectional, population-based survey in Vellore district to estimate the seroprevalence of scrub typhus in the community using immunoglobulin (Ig)G and IgM antibodies. We assessed the risk factors for acquiring the disease in the community in a case–control study. We also analysed the severity of disease and current management options among patients admitted to CMC. The study was approved by the Ethics Review Board of CMC.
Two specific serological tests, a Dot enzyme immunoassay (EIA) and an immunoglobulin (Ig)M enzyme... more Two specific serological tests, a Dot enzyme immunoassay (EIA) and an immunoglobulin (Ig)M enzyme-linked immunosorbent assay (ELISA) using the 56 kDa antigen and the Weil-Felix test were evaluated for diagnosis of scrub typhus. Sensitivity of 100, 86.5 and 43.5% were observed with Dot EIA, IgM ELISA and Weil-Felix test, respectively. False-positive reactions were observed in patients with falciparum malaria, pulmonary tuberculosis, S. viridans septicemia and typhoid fever using Dot EIA and IgM ELISA. Therefore, although Dot EIA and IgM ELISA are useful in the serodiagnosis of scrub typhus, efforts should be made to rule out other febrile illnesses.
Background: Peripheral nerve hyperexcitability (PNH) and neuromyotonia have been mainly attribute... more Background: Peripheral nerve hyperexcitability (PNH) and neuromyotonia have been mainly attributed to antibodies against voltage-gated potassium channels (VGKC). Concurrent autoimmune disorders, malignancies, and heavy metal toxicity have also been implicated. There is scarce mention about infection as a triggering factor for PNH. There are no reports of methicillin-resistant Staphylococcus aureus (MRSA) infection being a possible precipitating factor for development of PNH. Methods: Case series and literature review. Results: Four subjects were diagnosed to have features of PNH based on clinical and electrophysiological assessment. All the subjects had concurrent evidence of cutaneous abscesses requiring surgical intervention and antibiotic therapy. The cultures in all of them revealed growth of Staphylococcus aureus with three of them being MRSA isolates. Two subjects tested positive for anti-VGKC antibodies. There was remarkable resolution in neuromyotonia after antibiotics in three subjects. One subject succumbed to fulminant MRSA septicemia. Conclusion: There appears to be a definitive link between staphylococcal infection (MRSA in particular) and development of PNH. The temporal evolution of PNH associated with the infection and resolution following treatment of the infection does support a causal association. The enterotoxins produced by staphylococci act as superantigens and could trigger an inflammatory cascade along with development of cross reacting antibodies against VGKC in peripheral nerves. Future studies with animal models could provide more directions in this regard.
Commercial dengue virus (DENV) nonstructural-1 (NS1) Ag detection immunoassays often perform poor... more Commercial dengue virus (DENV) nonstructural-1 (NS1) Ag detection immunoassays often perform poorly, particularly in secondary DENV infection. To develop a highly sensitive NS1 ELISA, we generated a large repertoire of anti-DENV NS1 mouse mAbs (n = 95) that falls into 36 mAb classes based on binding specificities. The identified mAb pair, capable of efficiently detecting NS1 from four DENV serotypes in an immunoassay, was selected based on multiparametric analysis. The selected mAbs have subnanomolar affinities for NS1 with recognition sites outside the immunodominant wing domain. The assay was converted to an ELISA kit, which showed higher analytical sensitivity (3-fold to 83-fold) for NS1 from four DENV serotypes than commercial Platelia NS1 ELISA (Bio-Rad Laboratories). Compared to RT-PCR, the developed NS1 ELISA showed 78.57% (66 of 84) sensitivity, whereas Platelia NS1 ELISA showed a sensitivity of 60.71% (51 of 84). In a subgroup of RT-PCR–positive secondary dengue samples, ou...
Introduction: Skin colonization is a risk factor for multi-drug resistant (MDR) catheter-associat... more Introduction: Skin colonization is a risk factor for multi-drug resistant (MDR) catheter-associated bloodstream infections (CABSI). This study aimed to determine the prevalence and spectrum of skin colonizing MDR organisms in incident HD patients and their correlation with CABSI. Methods: This single-center prospective cohort study included consecutive adult incident HD patients who underwent tunneled or non-tunneled internal jugular vein HD catheter insertion between June 1, 2017 and October 31, 2017. Nasal, axillary, and exit site swabs were obtained prior to catheter insertion, at 14–21 days, and 28–35 days after catheter insertion. Results: Forty-three patients (69.7% male, 32.5% diabetic) were included and provided baseline swabs, while 29 and 10 patients respectively were available for follow-up swabs. MDR bacterial colonization, MRSA colonization, and MDR gram-negative colonization on the baseline set of swabs were seen in 76.7%, 69.7%, and 9.3% patients respectively. Of the 29 patients with at least two consecutive sets of swabs, 79.3% showed persistent colonization by MDR gram-positive organisms, most commonly by MRSA. Six patients developed a CABSI during the follow-up period (incidence rate 3.7 per 1000 patient days), 83.4% were gram negative, and in only one instance (16.6%) was the bacterial strain identical to that which had previously colonized the skin. Conclusions: Three-fourths of HD patients were colonized by MDR bacteria prior to HD initiation. Despite the majority being persistently colonized by MDR gram-positive organisms, CABSIs were predominantly gram negative.
Detection of Orientia tsutsugamushi DNA in a trombiculid mite chigger species suggests that it mi... more Detection of Orientia tsutsugamushi DNA in a trombiculid mite chigger species suggests that it might be a potential vector of scrub typhus in an endemic area. Over a period of 20 mo, 85 rats were trapped, 57 had chiggers that were identified by standard morphometric techniques. The chigger pools were assessed by performing PCR assays targeting fragments of the single-copy genes 56 kDa type-specific antigen gene (TSA56) by nested PCR and the 47 kDa (htrA) quantitative real-time PCR (qPCR). The novel traD SYBR green assay that detects a multicopy gene was also performed. In total, 27 chigger pools were positive by traD qPCR, of which only 7 were positive by 47 kDa qPCR and in 3 of these, 56 kDa gene was amplified by nested PCR. Orientia tsutsugamushi-specific DNA was detected in Ascoschoengastia spp., Schoengastiella ligula, Leptotrombidium rajasthanense, Leptotrombidium deliense, and Leptotrombidium jayawickremei chigger pools. Therefore, they could be potential vectors of scrub typh...
Spondylodiscitis is an infectious inflammation that affects the intervertebral disc and adjacent ... more Spondylodiscitis is an infectious inflammation that affects the intervertebral disc and adjacent structures. Treating infective spondylodiscitis is often challenging due to the lack of specific symptoms. Here we present an unusual case of infective spondylodiscitis caused by Campylobacter fetus subsp. fetus .
Background:: Antiretroviral therapy (ART) has led to a decline in autoimmune diseases but lacks s... more Background:: Antiretroviral therapy (ART) has led to a decline in autoimmune diseases but lacks studies on its effect on autoantibodies. Methods: It is a cross-sectional study with archived samples from 100 paired HIV-1 infected ART naïve and experienced individuals and 100 prospectively collected matched blood-donor controls. Antinuclear antibody, IgG anticardiolipin antibody, IgM and IgG β2 glycoprotein-1 antibodies, and total IgG levels were detected. Results are expressed as mean with standard deviation (SD), median, percentage positivity, and a p<0.05 is considered significant. The study was approved by the Institutional Review Board. Results: The median viral load of the treatment naïve samples was 4.34 Log copies/mL, while all were virally suppressed post ART with a median duration of treatment for 12 months (range: 3-36 months). The percentage of antinuclear antibody positivity was 5% among ART naïve and controls, with a decrease of 2% post ART (p= 0.441). The positivity ...
Rapid diagnostic test (RDT) kits are widely used in India for the diagnosis of dengue infection. ... more Rapid diagnostic test (RDT) kits are widely used in India for the diagnosis of dengue infection. It is important to evaluate the validity and reliability of these RDTs. The study was aimed to determine the sensitivity, specificity and predictive value of four commercially available RDTs [Panbio Dengue Duo cassette, Standard Diagnostics (SD) Bioline Dengue Duo, J. Mitra Dengue Day-1 test and Reckon Dengue IgG/IgM] against composite reference criteria (CRC), and compare the cost of the tests. In this prospective observational study for diagnostic accuracy, we tested stored blood samples from 132 cases of dengue and 149 controls of other infections as classified based on CRC, with all the four RDTs. The CRC was based on the epidemiological considerations, common clinical features and laboratory abnormalities. The non-dengue controls were the cases of proven alternative diagnosis. The diagnostic performances of the tests were compared in terms of sensitivity, specificity and predictive ...
The immunodominant TSA 56 gene ofOrientia tsutsugamushi, (scrub typhus agent) has four variable r... more The immunodominant TSA 56 gene ofOrientia tsutsugamushi, (scrub typhus agent) has four variable regions (VD-I to VD-IV) making it useful for genotyping. As of date the genotyping data from India is based on partial 56kDa gene sequence analysis. The complete TSA 56 gene sequence is important for knowing the circulating strains and for designing region specific diagnostics and vaccines. This study was undertaken to determineOrientia tsutsugamushigenotypes circulating in and around Vellore using complete and partial TSA 56 gene. Of the 379 whole blood samples from suspected scrub typhus patients, 162 were positive by 47 kDa qPCR. Long protocol to amplify the complete TSA 56 gene (≈1605 bp) was performed on 21 samples. On the same 21 samples the partial gene sequence was also amplified using the Horinouchi (≈650bp) and the Furuya (≈480 bp) protocol. Using a combination of Sanger and Nanopore technology complete sequence was obtained for 9 and near complete (1551 to 1596 bp) for 4 respec...
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