Aliabbas Husain - Academia.edu (original) (raw)

Papers by Aliabbas Husain

Basic and Clinical Neuroscience Journal, 2020

Introduction: The diagnosis of Tuberculous Meningitis (TBM) has remained a challenge due to its i... more Introduction: The diagnosis of Tuberculous Meningitis (TBM) has remained a challenge due to its insidious onset and the failure of conventional diagnostic tests. The present study aimed to identify the mycobacterial pathogen in the CSF of patients with TBM and a poor prognosis. Methods: We retrospectively recruited 224 TBM and 34 non-TBM patients admitted to the Central India Institute of Medical Sciences, Nagpur, India, in 2014. The CSF samples of these patients were subjected to a duplex PCR assay for the species-specific identification of the causative pathogen. Results: M. bovis and infection with M.tuberculosis were detected in 7% (18) and 32.9% (85) of the patients, respectively. Moreover, 14% (36) of the study samples were culture positive; however, the mycobacterial pathogens could not be differentiated to the species level. Conclusion: The present study findings emphasized the potentially vital importance of M. bovis identification for appropriate patient management. The o...

Brucellosis is an important zoonotic disease and has public health importance. In the present stu... more Brucellosis is an important zoonotic disease and has public health importance. In the present study, we studied the prevalence and associated risk factors of human brucellosis in the central Indian population from tertiary care health settings. A prospective observational study was conducted from March 2015 to February 2018 in patients attending the outpatient department (OPD) of Central India Institute of Medical Sciences (CIIMS), Nagpur. A total of 7026 individuals suspected of brucellosis were recruited based on prespecified inclusion criteria, additional risk factors, and clinical symptoms. Baseline, demographic and clinical characteristics were likewise recorded. Sera samples from recruited individuals were collected and subjected to anti-brucellosis antibody (IgM) detection using a commercial kit by ELISA assay. The overall seroprevalence of brucellosis reported from tertiary care health settings was 11% (772/7026). The majority of positive cases were from the states Madhya Pr...

Mycobacterium bovis (M. bovis) infection in humans is not adequately diagnosed since classical bi... more Mycobacterium bovis (M. bovis) infection in humans is not adequately diagnosed since classical biochemical and cultural tests are both sophisticated and time consuming. However, being intrinsically resistant to Pyrazinamide, the species-specific identification of M. bovis is clinically significant. The present study was performed to determine the prevalence of Zoonotic M. bovis-induced tuberculosis (TB) in the malnourished tribal population of Melghat using a duplex PCR assay targeting the regions of difference (RD) 1 and 4. A prospective cohort study was carried over a period of 2 years from 2011 to 2013 in the Melghat region of Maharashtra, India. A total number of 347 blood samples were collected from participants recruited through camps organized in 10 different villages of Melghat. The samples were then subjected to duplex PCR assay for differential identification of the mycobacterial pathogens viz., M. tuberculosis (M. tb), M. bovis and M. bovis BCG. The duplex PCR assay ident...

Vaccine, 2021

Tuberculosis (TB) is the leading infectious cause of death globally. The only licensed TB vaccine... more Tuberculosis (TB) is the leading infectious cause of death globally. The only licensed TB vaccine, Bacille Calmette-Guérin (BCG), has low efficacy against TB in adults and is not recommended in people with impaired immunity. The incorporation of the Mycobacterium tuberculosis (Mtb) secretion system ESX-1 into BCG improves immunogenicity and protection against TB in animal models, which is associated with the secretion of the ESX-1-dependent protein ESAT-6. However, the resulting strain, BCG::ESX1Mtb, has been deemed unsafe as a human vaccine, due to prolonged persistence and increased virulence in immunocompromised mice. In this study, we describe a new recombinant BCG strain that uncouples the beneficial aspects of ESAT-6 secretion from the detrimental ESX-1effects on virulence and persistence. The strain was constructed by fusing the ESAT-6-encoding gene esxA to the general secretion signal for the mycobacterial type VII secretion pathway protein PE25. This new strain, BCG::ESAT6-PE25SS, secretes full-length ESAT-6 via the ESX-5 secretion system, which in contrast to ESX-1 is also present in BCG. In vivo testing revealed that ESX-5-targeted ESAT-6 export, induces cytosolic contact, generates ESAT-6-specific T cells and enhances the protective efficacy against TB disease, but is associated with low virulence and reduced persistence in immunocompetent and immunocompromised mice. Additionally, compared to BCG::ESX1Mtb and parental BCG, mucosal administration of BCG::ESAT6-PE25SS is associated with more rapid clearance from the lung. These results warrant further studies to evaluate BCG::ESAT6-PE25SS as a potential live attenuated vaccine candidate for TB.

Journal of Pharmaceutical Research International, 2021

Background: Latent TB infection (LTBI) is an infection where the presence of disease causing orga... more Background: Latent TB infection (LTBI) is an infection where the presence of disease causing organism M. tuberculosis is there without any sign and symptoms of the disease hence mostly remains undiagnosed, though Tuberculin skin test (TST) and Interferon Gamma Release Assay (IGRA) were used to diagnose the LTBI. They have their limitations, TST gives major cross-reactivity with BCG vaccine and gives inaccurate results in individuals who have taken BCG and IGRA are very costly and variable sensitivity is repeated in various populations hence the modifications are needed in the IGRA for proper diagnosis of LTBI. Objectives: In the proposed study we aimed to develop an improved whole blood assay towards a diagnosis of latent and active TB infection as an alternative to the Quantiferon QFT assay Methodology: Synthetic antigenic peptides against latency specific antigens will be designed and synthesized. Designed peptides will be screened for LTBI specific cytokine by ...

Journal of Pharmaceutical Research International, 2021

Background: Bacterial meningitis (BM) is severe complication of central nervous system (CNS) and ... more Background: Bacterial meningitis (BM) is severe complication of central nervous system (CNS) and is often associated with high mortality and morbidity rates if not timely diagnosed and treated. Current diagnostic tools for BM and drug resistance suffer from lack of sensitivity due to paucibacillary nature of Cerebrospinal fluid (CSF). Objectives: The objective of the study is to develop rapid and efficacious immunological tools (Enzyme linked immunosorbent assay and Lateral flow) for diagnosis of BM in hospital settings. In addition, in-house molecular assays will be developed for diagnosis of extended spectrum beta lactamases and Carbapenems drug resistance in community and hospital acquired BM infection Methodology: A prospective observational study will be carried out in patients admitted in IPD awards of CIIMS, Nagpur. Diagnosis of BM will be done using conventional gold standards and by in-house designed nested polymerase chain reaction (PCR) for 8 etiological pathogens. An in-...

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) viru... more The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) virus has emerged as public health emergency affecting 206 countries worldwide. India is second highest currently worst effected by Covid 19 pandemic with close to 12.6 million cases and 1.6K deaths reported till date. Maharahstra is the highest Covid-19 burden state in India reporting quarter of overall cases. The city of Nagpur, in Maharashtra state, ranks 4th in terms of reported COVID-19 cases, with 2.5 lakh incidences and more than 4,000 deaths As the transmission rate of COVID-19 is high, it is imperative to study its disease epidemiology in regions of high endemicity to bolster our understanding of its spread, transmission dynamics and contact tracing to undertake appropriate public health control measures.. The present study was undertaken to study the incidence and trend of COVID-19 infection from various zonal regions of Nagpur city, using real time PCR (RT PCR). A retrospective st...

Clinical Microbiology and Infection, 2021

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Epidemiology and Health, 2021

India has a higher tuberculosis (TB) burden than any other country, accounting for an estimated o... more India has a higher tuberculosis (TB) burden than any other country, accounting for an estimated one-fourth of the global burden. Drug-resistant tuberculosis (DR-TB) presents a major public health problem in India. Patients with DR-TB often require profound changes in their drug regimens, which are invariably linked to poor treatment adherence and sub-optimal treatment outcomes compared to drug-sensitive TB. The challenge of addressing DR-TB is critical for India, as India contributes over 27% of global DR-TB cases. In recent decades, India has been proactive in its battle against TB, even implementing a revised National Strategic Plan to eliminate TB by 2025. However, to achieve this ambitious goal, the country will need to take a multifaceted approach with respect to its management of DR-TB. Despite concerted efforts made by the National TB Elimination Program, India faces substantial challenges with regard to DR-TB care, especially in peripheral and resource-limited endemic zones....

Malaysian Journal of Medical Sciences, 2020

Background: Human brucellosis is an important zoonotic disease of public health and often remains... more Background: Human brucellosis is an important zoonotic disease of public health and often remains neglected owing to lack of sensitive and efficient diagnostic methods. This study evaluates diagnostic utility of in-house designed enzyme-linked immunosorbent assay (ELISA) using whole-cell antigens of Brucella abortus (B. abortus) S19 against the commercially available kits. Methods: A prospective cohort study involving different populations within the Vidarbha regions of Maharashtra, India was conducted through camps organised from May 2009 to October 2015. A total of 568 serum samples were collected from high-risk people recruited as study cohorts based on inclusion criteria, additional risk factors and clinical symptoms. Samples were evaluated by indirect ELISA using the whole-cell antigens of B. abortus. The results were compared with the commercially available IgG detection ELISA kit to ascertain the specificity and sensitivity of the developed test. Results: Fever, body ache, jo...

JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH, 2018

Brucellosis has remained an emerging yet neglected zoonotic disease in humans worldwide. In devel... more Brucellosis has remained an emerging yet neglected zoonotic disease in humans worldwide. In developing nations like India, brucellosis remains an uncontrolled and major public health problem. The disease is mainly transmitted to humans through the ingestion of raw or unpasteurised milk and milk products contaminated with Brucella species. A wide incidence of human brucellosis in India is described in many studies ranging from 0.8% in Kashmir and 26.6% in Ludhiana [1]. In 5-10% of cases, existing infection may contribute to severe complications of the Central Nervous System (CNS) known as neurobrucellosis [2-4]. Neurobrucellosis is a rare disease and can be misdiagnosed clinically with neurological complications of other diseases of bacterial and viral origin. Despite being a rare complication of brucellosis, neurobrucellosis can be a major cause of neurological morbidity and mortality if not promptly recognised and treated. Various studies suggest that CNS involvement of brucellosis can lead to encephalitis, meningoencephalitis, radiculitis, myelitis, peripheral and cranial neuropathies, subarachnoid haemorrhage, and psychiatric manifestations [5-10]. Diagnostic criteria for neurobrucellosis are often challenging. Existing tests for diagnosis of neurobrucellosis in CSF such as culture, and molecular tests suffer from sensitivity and specificity limitation due to the paucibacillary nature of the disease. Also, such tests requires elaborate infrastructural facilities which are way beyond reach for most of the diagnostic capacities in low resource settings in India [11,12]. Development of rapid and sensitive tests that can be carried out with minimal sample volume would greatly reduce diagnostic constraints and treatment delays associated with brucellosis. Detection of Brucella specific antibodies in CSF using ELISA technique is rapid, highly sensitive, cost effective and can readily be set up in a laboratory with minimum resources [11]. Such tests can be utilised along with other diagnostic protocols for screening the incidence and confirmatory diagnosis of neurobrucellosis. In the present study, we report utility of antibody based immunoassay protocol for diagnosis and incidence of neurobrucellosis in suspected cases with neurological complications in our hospital. MAtERIALS And MEthOdS Study design and Participant Recruitment This was a prospective cohort study conducted on 280 patients admitted to the Neurology Department of the Central India Institute of Medical Sciences (CIIMS), Nagpur, Maharashtra, India (from the April 2015 to March 2016). Patients showing infectious/non infectious neurological disorders were referred to the Neurology Department of CIIMS from different primary and secondary health centres where more than 1000 CSF samples were withdrawn and analysed annually. Out of 280 cases, 79 patients were excluded from the study as these patients showed no exposure to neurobrucellosis risk-factors. Further 88 cases showing mixed infection other than brucellosis were ruled out from the study. Out of 113 cases, 31 Pallavi a TemBhurne 1 , ajaz S ali 2 , aliaBBaS a huSain 3 , haTim F Daginawala 4 , lokenDra r Singh 5 , rajPal S kaShyaP 6

Journal of Epidemiology and Global Health, 2017

In the present study, we aimed to estimate the occurrence of bovine tuberculosis (TB) and examine... more In the present study, we aimed to estimate the occurrence of bovine tuberculosis (TB) and examine the determinants of distribution of the disease in three high-risk populations of Central India. A prospective cohort study was conducted in Central India between March 2014 and June 2015. Based on the requisite inclusion criteria, we recruited a total of 301 participants whose blood samples were subjected to polymerase chain reaction-based detection and differentiation of Mycobacterium bovis and Mycobacterium tuberculosis. M. bovis was detected in 11.4%, 8.9%, and 12.6% of the recruited participants belonging to three distinct population groups (Groups A, B, and C, respectively). The highest proportion of cases infected with M. bovis was observed in Group C, who lived in the high TB endemic region. Previous contact with active TB cases (odds ratio = 3.7; 95% confidence interval, 0.9612-14.4533) and raw milk consumption (odds ratio = 5.3472; 95% confidence interval, 1.9590-14.5956) were found to be important determinants of bovine TB in this population. The high incidence rates of bovine TB in the Central Indian populations indicate the substantial consequences of this disease for some population groups and settings. However, more research is necessary to identify the main transmission drivers in these areas.

Lung India, 2016

and among these, 5-10% are at lifetime risk of progressing to the active TB. [3] Laboratory tests... more and among these, 5-10% are at lifetime risk of progressing to the active TB. [3] Laboratory tests aiding early and rapid diagnosis along with efficient treatment against LTBI are therefore required to minimize the burden of TB in India. INTRODUCTION An estimated 40% of Indian population harbors Mycobacterium tuberculosis (MTB) infection, making India among the top five countries with high TB incidence cases on a global scale. [1,2] Once infected with MTB, ~30% of the individuals develops latent tuberculosis infection (LTBI) Aims: To study socioeconomic status (SES) and living conditions (LC) as risk factors for latent tuberculosis infection (LTBI) and their impact on QuantiFERON-TB gold (QFT-G) and tuberculin skin test (TST) outcome for determining a better diagnostic test for LTBI in the malnourished tribal population of Melghat. Settings and Design: Six hundred sixty nine participants matching the inclusion criteria were recruited from 10 tribal villages of Melghat region, India. Subjects and Methods: Complete information related to various risk factors and test outcome was obtained on 398 participants, which was analyzed as per predefined conceptual framework. Factors were classified based on their relevance either at individual or household level, and subsequently based on the possibility of intervention. Data were partitioned into concordant and discordant sets depending on test agreement. Results: In concordant set, the two tests revealed that LTBI was significantly associated with smoking (adjusted odds ratio [aOR]: 2.64 [95% confidence interval [CI]: 1.03-6.79]), tobacco usage (aOR: 2.74 [95% CI: 1.50-4.99]), and malnourishment (aOR: 1.97 [95% CI: 1.12-3.48]) after basic adjustment. Inclusion of latent variable SES and LC in the model has mediating effect on the association of above factors with LTBI. Further, the association of SES and LC with LTBI in concordant set was unaltered in presence of other cofactors. From discordant set, results of QFT-G corroborated with that of concordant set. Conclusions: Poor SES and LC can be considered as strong risk factors linked with LTBI as compared to malnourishment, which is often targeted in such communities. Further, our study showed QFT-G test as a reliable tool in screening of LTBI in the tribal population of Melghat, India.

Tuberculosis, 2016

Tuberculosis (TB) continues to be a global epidemic, despite of the availability of Bacillus Calm... more Tuberculosis (TB) continues to be a global epidemic, despite of the availability of Bacillus Calmette Guerin (BCG) vaccine for more than six decades. In an effort to eradicate TB, vaccinologist around the world have made considerable efforts to develop improved vaccine candidates, based on the understanding of BCG failure in developing world and immune response thought to be protective against TB. The present review represents a current perspective on TB vaccination research, including additional research strategies needed for increasing the efficacy of BCG, and for the development of new effective vaccines for high TB endemic regions.

Clinical and Experimental Vaccine Research, 2016

In the present study, the protective immunological markers in serum and peripheral blood mononucl... more In the present study, the protective immunological markers in serum and peripheral blood mononuclear cells (PBMCs) of bacillus Calmette-Guérin (BCG) vaccinated and unvaccinated children were evaluated after vaccination. Further, PBMCs of children with low protective levels were boosted with BCG, Ag85B, and Ag85B peptides to study their booster effects to increase waning BCG induced immunity. Materials and Methods: Fifty children from 1 month to 18 years of age were randomized for the study. Blood samples were collected from 27 participants with/without BCG vaccination. Immunological markers (anti-BCG, interferon γ [IFN-γ], and adenosine deaminase activity) were assessed in both serum and PBMCs of children. Children with low levels of protective immunological markers were further recruited and their PBMCs were boosted with BCG, Ag85B, and Ag85B peptides. Results: Children in age group of 4-6 years were associated with significantly (p<0.05) higher BCG-specific IgG and IFN-γ levels compared to those in age group greater than 10 years. Vaccinated children had greater repertoire of immunological memory which on in vitro stimulation with BCG showed increase in BCG-specific response compared to unvaccinated controls. Assessment of booster effects of BCG, Ag85B, and Ag85B peptides in PBMCs of children revealed greater potential of peptides to boost BCG induced immunity compared to BCG and Ag85B. Conclusion: To conclude, children within age 4-6 years are associated with high immunological markers which eventually diminish with age thereby suggesting need for booster dose in later years. Mycobacterium tuberculosis peptides along with BCG may be used as attractive candidates to boost such waning BCG induced immunity in children.

International Journal of Peptide Research and Therapeutics, 2015

Limited experimental evidences are available on the use of peptides as vaccines to boost BCG indu... more Limited experimental evidences are available on the use of peptides as vaccines to boost BCG induced immunity for protection against tuberculosis. The present study therefore evaluated protective efficacy of booster dose of N-terminal peptides of Ag85B, using prime boost approaches in murine model of tuberculosis. Using earlier established subcutaneous murine model of TB in our laboratory, we compared the protective vaccination efficacy of peptides of Ag85B with that of booster dose of whole Ag85B and BCG by evaluating both antibody and cellmediated immune response. Groups of mice primed by BCG and boosted with Ag85B peptides showed limited pulmonary bacillary burden and reduced lung pathology after challenge with virulent dose of Mycobacterium tuberculosis in mice. Significant levels (p \ 0.001) of BCG specific antibodies (anti-BCG, anti-PPD) and T cellspecific cytokines were observed in Ag85B peptides boosted mice compared to Ag85B and BCG. Ag85B and BCG boosted mice however showed significant protection compared to single BCG dose and unvaccinated control groups. Our result suggests that prime boost strategy using N-terminal peptides of Ag85B may improve immunogenicity of BCG against TB. Such peptides may be attractive candidates for boosting waning BCG induced immune response in near future. However study demands further work including improvisation in experimental designs to justify the results.

PloS one, 2015

Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the ch... more Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-ass...

JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH, 2015

Basic and Clinical Neuroscience Journal, 2020

Introduction: The diagnosis of Tuberculous Meningitis (TBM) has remained a challenge due to its i... more Introduction: The diagnosis of Tuberculous Meningitis (TBM) has remained a challenge due to its insidious onset and the failure of conventional diagnostic tests. The present study aimed to identify the mycobacterial pathogen in the CSF of patients with TBM and a poor prognosis. Methods: We retrospectively recruited 224 TBM and 34 non-TBM patients admitted to the Central India Institute of Medical Sciences, Nagpur, India, in 2014. The CSF samples of these patients were subjected to a duplex PCR assay for the species-specific identification of the causative pathogen. Results: M. bovis and infection with M.tuberculosis were detected in 7% (18) and 32.9% (85) of the patients, respectively. Moreover, 14% (36) of the study samples were culture positive; however, the mycobacterial pathogens could not be differentiated to the species level. Conclusion: The present study findings emphasized the potentially vital importance of M. bovis identification for appropriate patient management. The o...

Brucellosis is an important zoonotic disease and has public health importance. In the present stu... more Brucellosis is an important zoonotic disease and has public health importance. In the present study, we studied the prevalence and associated risk factors of human brucellosis in the central Indian population from tertiary care health settings. A prospective observational study was conducted from March 2015 to February 2018 in patients attending the outpatient department (OPD) of Central India Institute of Medical Sciences (CIIMS), Nagpur. A total of 7026 individuals suspected of brucellosis were recruited based on prespecified inclusion criteria, additional risk factors, and clinical symptoms. Baseline, demographic and clinical characteristics were likewise recorded. Sera samples from recruited individuals were collected and subjected to anti-brucellosis antibody (IgM) detection using a commercial kit by ELISA assay. The overall seroprevalence of brucellosis reported from tertiary care health settings was 11% (772/7026). The majority of positive cases were from the states Madhya Pr...

Mycobacterium bovis (M. bovis) infection in humans is not adequately diagnosed since classical bi... more Mycobacterium bovis (M. bovis) infection in humans is not adequately diagnosed since classical biochemical and cultural tests are both sophisticated and time consuming. However, being intrinsically resistant to Pyrazinamide, the species-specific identification of M. bovis is clinically significant. The present study was performed to determine the prevalence of Zoonotic M. bovis-induced tuberculosis (TB) in the malnourished tribal population of Melghat using a duplex PCR assay targeting the regions of difference (RD) 1 and 4. A prospective cohort study was carried over a period of 2 years from 2011 to 2013 in the Melghat region of Maharashtra, India. A total number of 347 blood samples were collected from participants recruited through camps organized in 10 different villages of Melghat. The samples were then subjected to duplex PCR assay for differential identification of the mycobacterial pathogens viz., M. tuberculosis (M. tb), M. bovis and M. bovis BCG. The duplex PCR assay ident...

Vaccine, 2021

Tuberculosis (TB) is the leading infectious cause of death globally. The only licensed TB vaccine... more Tuberculosis (TB) is the leading infectious cause of death globally. The only licensed TB vaccine, Bacille Calmette-Guérin (BCG), has low efficacy against TB in adults and is not recommended in people with impaired immunity. The incorporation of the Mycobacterium tuberculosis (Mtb) secretion system ESX-1 into BCG improves immunogenicity and protection against TB in animal models, which is associated with the secretion of the ESX-1-dependent protein ESAT-6. However, the resulting strain, BCG::ESX1Mtb, has been deemed unsafe as a human vaccine, due to prolonged persistence and increased virulence in immunocompromised mice. In this study, we describe a new recombinant BCG strain that uncouples the beneficial aspects of ESAT-6 secretion from the detrimental ESX-1effects on virulence and persistence. The strain was constructed by fusing the ESAT-6-encoding gene esxA to the general secretion signal for the mycobacterial type VII secretion pathway protein PE25. This new strain, BCG::ESAT6-PE25SS, secretes full-length ESAT-6 via the ESX-5 secretion system, which in contrast to ESX-1 is also present in BCG. In vivo testing revealed that ESX-5-targeted ESAT-6 export, induces cytosolic contact, generates ESAT-6-specific T cells and enhances the protective efficacy against TB disease, but is associated with low virulence and reduced persistence in immunocompetent and immunocompromised mice. Additionally, compared to BCG::ESX1Mtb and parental BCG, mucosal administration of BCG::ESAT6-PE25SS is associated with more rapid clearance from the lung. These results warrant further studies to evaluate BCG::ESAT6-PE25SS as a potential live attenuated vaccine candidate for TB.

Journal of Pharmaceutical Research International, 2021

Background: Latent TB infection (LTBI) is an infection where the presence of disease causing orga... more Background: Latent TB infection (LTBI) is an infection where the presence of disease causing organism M. tuberculosis is there without any sign and symptoms of the disease hence mostly remains undiagnosed, though Tuberculin skin test (TST) and Interferon Gamma Release Assay (IGRA) were used to diagnose the LTBI. They have their limitations, TST gives major cross-reactivity with BCG vaccine and gives inaccurate results in individuals who have taken BCG and IGRA are very costly and variable sensitivity is repeated in various populations hence the modifications are needed in the IGRA for proper diagnosis of LTBI. Objectives: In the proposed study we aimed to develop an improved whole blood assay towards a diagnosis of latent and active TB infection as an alternative to the Quantiferon QFT assay Methodology: Synthetic antigenic peptides against latency specific antigens will be designed and synthesized. Designed peptides will be screened for LTBI specific cytokine by ...

Journal of Pharmaceutical Research International, 2021

Background: Bacterial meningitis (BM) is severe complication of central nervous system (CNS) and ... more Background: Bacterial meningitis (BM) is severe complication of central nervous system (CNS) and is often associated with high mortality and morbidity rates if not timely diagnosed and treated. Current diagnostic tools for BM and drug resistance suffer from lack of sensitivity due to paucibacillary nature of Cerebrospinal fluid (CSF). Objectives: The objective of the study is to develop rapid and efficacious immunological tools (Enzyme linked immunosorbent assay and Lateral flow) for diagnosis of BM in hospital settings. In addition, in-house molecular assays will be developed for diagnosis of extended spectrum beta lactamases and Carbapenems drug resistance in community and hospital acquired BM infection Methodology: A prospective observational study will be carried out in patients admitted in IPD awards of CIIMS, Nagpur. Diagnosis of BM will be done using conventional gold standards and by in-house designed nested polymerase chain reaction (PCR) for 8 etiological pathogens. An in-...

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) viru... more The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) virus has emerged as public health emergency affecting 206 countries worldwide. India is second highest currently worst effected by Covid 19 pandemic with close to 12.6 million cases and 1.6K deaths reported till date. Maharahstra is the highest Covid-19 burden state in India reporting quarter of overall cases. The city of Nagpur, in Maharashtra state, ranks 4th in terms of reported COVID-19 cases, with 2.5 lakh incidences and more than 4,000 deaths As the transmission rate of COVID-19 is high, it is imperative to study its disease epidemiology in regions of high endemicity to bolster our understanding of its spread, transmission dynamics and contact tracing to undertake appropriate public health control measures.. The present study was undertaken to study the incidence and trend of COVID-19 infection from various zonal regions of Nagpur city, using real time PCR (RT PCR). A retrospective st...

Clinical Microbiology and Infection, 2021

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Epidemiology and Health, 2021

India has a higher tuberculosis (TB) burden than any other country, accounting for an estimated o... more India has a higher tuberculosis (TB) burden than any other country, accounting for an estimated one-fourth of the global burden. Drug-resistant tuberculosis (DR-TB) presents a major public health problem in India. Patients with DR-TB often require profound changes in their drug regimens, which are invariably linked to poor treatment adherence and sub-optimal treatment outcomes compared to drug-sensitive TB. The challenge of addressing DR-TB is critical for India, as India contributes over 27% of global DR-TB cases. In recent decades, India has been proactive in its battle against TB, even implementing a revised National Strategic Plan to eliminate TB by 2025. However, to achieve this ambitious goal, the country will need to take a multifaceted approach with respect to its management of DR-TB. Despite concerted efforts made by the National TB Elimination Program, India faces substantial challenges with regard to DR-TB care, especially in peripheral and resource-limited endemic zones....

Malaysian Journal of Medical Sciences, 2020

Background: Human brucellosis is an important zoonotic disease of public health and often remains... more Background: Human brucellosis is an important zoonotic disease of public health and often remains neglected owing to lack of sensitive and efficient diagnostic methods. This study evaluates diagnostic utility of in-house designed enzyme-linked immunosorbent assay (ELISA) using whole-cell antigens of Brucella abortus (B. abortus) S19 against the commercially available kits. Methods: A prospective cohort study involving different populations within the Vidarbha regions of Maharashtra, India was conducted through camps organised from May 2009 to October 2015. A total of 568 serum samples were collected from high-risk people recruited as study cohorts based on inclusion criteria, additional risk factors and clinical symptoms. Samples were evaluated by indirect ELISA using the whole-cell antigens of B. abortus. The results were compared with the commercially available IgG detection ELISA kit to ascertain the specificity and sensitivity of the developed test. Results: Fever, body ache, jo...

JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH, 2018

Brucellosis has remained an emerging yet neglected zoonotic disease in humans worldwide. In devel... more Brucellosis has remained an emerging yet neglected zoonotic disease in humans worldwide. In developing nations like India, brucellosis remains an uncontrolled and major public health problem. The disease is mainly transmitted to humans through the ingestion of raw or unpasteurised milk and milk products contaminated with Brucella species. A wide incidence of human brucellosis in India is described in many studies ranging from 0.8% in Kashmir and 26.6% in Ludhiana [1]. In 5-10% of cases, existing infection may contribute to severe complications of the Central Nervous System (CNS) known as neurobrucellosis [2-4]. Neurobrucellosis is a rare disease and can be misdiagnosed clinically with neurological complications of other diseases of bacterial and viral origin. Despite being a rare complication of brucellosis, neurobrucellosis can be a major cause of neurological morbidity and mortality if not promptly recognised and treated. Various studies suggest that CNS involvement of brucellosis can lead to encephalitis, meningoencephalitis, radiculitis, myelitis, peripheral and cranial neuropathies, subarachnoid haemorrhage, and psychiatric manifestations [5-10]. Diagnostic criteria for neurobrucellosis are often challenging. Existing tests for diagnosis of neurobrucellosis in CSF such as culture, and molecular tests suffer from sensitivity and specificity limitation due to the paucibacillary nature of the disease. Also, such tests requires elaborate infrastructural facilities which are way beyond reach for most of the diagnostic capacities in low resource settings in India [11,12]. Development of rapid and sensitive tests that can be carried out with minimal sample volume would greatly reduce diagnostic constraints and treatment delays associated with brucellosis. Detection of Brucella specific antibodies in CSF using ELISA technique is rapid, highly sensitive, cost effective and can readily be set up in a laboratory with minimum resources [11]. Such tests can be utilised along with other diagnostic protocols for screening the incidence and confirmatory diagnosis of neurobrucellosis. In the present study, we report utility of antibody based immunoassay protocol for diagnosis and incidence of neurobrucellosis in suspected cases with neurological complications in our hospital. MAtERIALS And MEthOdS Study design and Participant Recruitment This was a prospective cohort study conducted on 280 patients admitted to the Neurology Department of the Central India Institute of Medical Sciences (CIIMS), Nagpur, Maharashtra, India (from the April 2015 to March 2016). Patients showing infectious/non infectious neurological disorders were referred to the Neurology Department of CIIMS from different primary and secondary health centres where more than 1000 CSF samples were withdrawn and analysed annually. Out of 280 cases, 79 patients were excluded from the study as these patients showed no exposure to neurobrucellosis risk-factors. Further 88 cases showing mixed infection other than brucellosis were ruled out from the study. Out of 113 cases, 31 Pallavi a TemBhurne 1 , ajaz S ali 2 , aliaBBaS a huSain 3 , haTim F Daginawala 4 , lokenDra r Singh 5 , rajPal S kaShyaP 6

Journal of Epidemiology and Global Health, 2017

In the present study, we aimed to estimate the occurrence of bovine tuberculosis (TB) and examine... more In the present study, we aimed to estimate the occurrence of bovine tuberculosis (TB) and examine the determinants of distribution of the disease in three high-risk populations of Central India. A prospective cohort study was conducted in Central India between March 2014 and June 2015. Based on the requisite inclusion criteria, we recruited a total of 301 participants whose blood samples were subjected to polymerase chain reaction-based detection and differentiation of Mycobacterium bovis and Mycobacterium tuberculosis. M. bovis was detected in 11.4%, 8.9%, and 12.6% of the recruited participants belonging to three distinct population groups (Groups A, B, and C, respectively). The highest proportion of cases infected with M. bovis was observed in Group C, who lived in the high TB endemic region. Previous contact with active TB cases (odds ratio = 3.7; 95% confidence interval, 0.9612-14.4533) and raw milk consumption (odds ratio = 5.3472; 95% confidence interval, 1.9590-14.5956) were found to be important determinants of bovine TB in this population. The high incidence rates of bovine TB in the Central Indian populations indicate the substantial consequences of this disease for some population groups and settings. However, more research is necessary to identify the main transmission drivers in these areas.

Lung India, 2016

and among these, 5-10% are at lifetime risk of progressing to the active TB. [3] Laboratory tests... more and among these, 5-10% are at lifetime risk of progressing to the active TB. [3] Laboratory tests aiding early and rapid diagnosis along with efficient treatment against LTBI are therefore required to minimize the burden of TB in India. INTRODUCTION An estimated 40% of Indian population harbors Mycobacterium tuberculosis (MTB) infection, making India among the top five countries with high TB incidence cases on a global scale. [1,2] Once infected with MTB, ~30% of the individuals develops latent tuberculosis infection (LTBI) Aims: To study socioeconomic status (SES) and living conditions (LC) as risk factors for latent tuberculosis infection (LTBI) and their impact on QuantiFERON-TB gold (QFT-G) and tuberculin skin test (TST) outcome for determining a better diagnostic test for LTBI in the malnourished tribal population of Melghat. Settings and Design: Six hundred sixty nine participants matching the inclusion criteria were recruited from 10 tribal villages of Melghat region, India. Subjects and Methods: Complete information related to various risk factors and test outcome was obtained on 398 participants, which was analyzed as per predefined conceptual framework. Factors were classified based on their relevance either at individual or household level, and subsequently based on the possibility of intervention. Data were partitioned into concordant and discordant sets depending on test agreement. Results: In concordant set, the two tests revealed that LTBI was significantly associated with smoking (adjusted odds ratio [aOR]: 2.64 [95% confidence interval [CI]: 1.03-6.79]), tobacco usage (aOR: 2.74 [95% CI: 1.50-4.99]), and malnourishment (aOR: 1.97 [95% CI: 1.12-3.48]) after basic adjustment. Inclusion of latent variable SES and LC in the model has mediating effect on the association of above factors with LTBI. Further, the association of SES and LC with LTBI in concordant set was unaltered in presence of other cofactors. From discordant set, results of QFT-G corroborated with that of concordant set. Conclusions: Poor SES and LC can be considered as strong risk factors linked with LTBI as compared to malnourishment, which is often targeted in such communities. Further, our study showed QFT-G test as a reliable tool in screening of LTBI in the tribal population of Melghat, India.

Tuberculosis, 2016

Tuberculosis (TB) continues to be a global epidemic, despite of the availability of Bacillus Calm... more Tuberculosis (TB) continues to be a global epidemic, despite of the availability of Bacillus Calmette Guerin (BCG) vaccine for more than six decades. In an effort to eradicate TB, vaccinologist around the world have made considerable efforts to develop improved vaccine candidates, based on the understanding of BCG failure in developing world and immune response thought to be protective against TB. The present review represents a current perspective on TB vaccination research, including additional research strategies needed for increasing the efficacy of BCG, and for the development of new effective vaccines for high TB endemic regions.

Clinical and Experimental Vaccine Research, 2016

In the present study, the protective immunological markers in serum and peripheral blood mononucl... more In the present study, the protective immunological markers in serum and peripheral blood mononuclear cells (PBMCs) of bacillus Calmette-Guérin (BCG) vaccinated and unvaccinated children were evaluated after vaccination. Further, PBMCs of children with low protective levels were boosted with BCG, Ag85B, and Ag85B peptides to study their booster effects to increase waning BCG induced immunity. Materials and Methods: Fifty children from 1 month to 18 years of age were randomized for the study. Blood samples were collected from 27 participants with/without BCG vaccination. Immunological markers (anti-BCG, interferon γ [IFN-γ], and adenosine deaminase activity) were assessed in both serum and PBMCs of children. Children with low levels of protective immunological markers were further recruited and their PBMCs were boosted with BCG, Ag85B, and Ag85B peptides. Results: Children in age group of 4-6 years were associated with significantly (p<0.05) higher BCG-specific IgG and IFN-γ levels compared to those in age group greater than 10 years. Vaccinated children had greater repertoire of immunological memory which on in vitro stimulation with BCG showed increase in BCG-specific response compared to unvaccinated controls. Assessment of booster effects of BCG, Ag85B, and Ag85B peptides in PBMCs of children revealed greater potential of peptides to boost BCG induced immunity compared to BCG and Ag85B. Conclusion: To conclude, children within age 4-6 years are associated with high immunological markers which eventually diminish with age thereby suggesting need for booster dose in later years. Mycobacterium tuberculosis peptides along with BCG may be used as attractive candidates to boost such waning BCG induced immunity in children.

International Journal of Peptide Research and Therapeutics, 2015

Limited experimental evidences are available on the use of peptides as vaccines to boost BCG indu... more Limited experimental evidences are available on the use of peptides as vaccines to boost BCG induced immunity for protection against tuberculosis. The present study therefore evaluated protective efficacy of booster dose of N-terminal peptides of Ag85B, using prime boost approaches in murine model of tuberculosis. Using earlier established subcutaneous murine model of TB in our laboratory, we compared the protective vaccination efficacy of peptides of Ag85B with that of booster dose of whole Ag85B and BCG by evaluating both antibody and cellmediated immune response. Groups of mice primed by BCG and boosted with Ag85B peptides showed limited pulmonary bacillary burden and reduced lung pathology after challenge with virulent dose of Mycobacterium tuberculosis in mice. Significant levels (p \ 0.001) of BCG specific antibodies (anti-BCG, anti-PPD) and T cellspecific cytokines were observed in Ag85B peptides boosted mice compared to Ag85B and BCG. Ag85B and BCG boosted mice however showed significant protection compared to single BCG dose and unvaccinated control groups. Our result suggests that prime boost strategy using N-terminal peptides of Ag85B may improve immunogenicity of BCG against TB. Such peptides may be attractive candidates for boosting waning BCG induced immune response in near future. However study demands further work including improvisation in experimental designs to justify the results.

PloS one, 2015

Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the ch... more Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-ass...

JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH, 2015