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Ocular manifestations and human immunodeficiency virus retinopathy in patients with acquired immunodeficiency syndrome in North India
(2006) V. Satya Suresh Attili; Vijay P. Singh; A.V. Bhaskar Reddy; Datla V. Varma; Madhukar Rai; Kumar A. Gulati; Shyam Sundar
Aim: To evaluate the spectrum of eye diseases in patients with human immunodeficiency virus, with special reference to human immunodeficiency virus retinopathy and its risk factors. Methods: All patient with human immunodeficiency virus attending the Infectious Disease Clinic at Sir Sunderlal Hospital, Institute of Medical Sciences, Banaras Hindu University, India, between January 2001 and December 2003 were enrolled. All patients underwent a thorough eye examination. Patients with acquired immunodeficiency syndrome retinopathy were analysed separately for predisposing factors. The risk factors analysed were positive C-reactive protein, low CD4 levels, associated central nervous system infections, and other eye diseases. Statistical analysis was done using Medcalc version 7.5. Results: Of 460 analysable patients, 88 patients (19%) had some eye manifestations, and 54 patients had human immunodeficiency virus retinopathy. Univariate analysis disclosed that immunosuppression (CD4 levels, <20/μL), positive C-reactive protein, associated eye lesions, and any central nervous system pathology were significant risk factors for the development of human immunodeficiency virus/acquired immunodeficiency syndrome retinopathy. Conclusions: Human immunodeficiency virus could be a risk factor for retinopathy as a significant number of patients did not have any other findings or risk factors for the development of retinopathy. However, it would be premature to draw definitive conclusions about the risk factors, as the number of patients analysed was small. © 2006 Scientific Communications International Limited.
Assessing L. donovani Skin Parasite Load: A Proof of Concept Study of a Microbiopsy Device in an Indian Setting
(Frontiers Media S.A., 2021) Kristien Cloots; Om Prakash Singh; Abhishek Kumar Singh; Gert Van der Auwera; Prashant Kumar; Mallikarjuna Rao Gedda; Tulika Kumari Rai; Epco Hasker; Shyam Sundar; Marleen Boelaert
Background: In the endgame of the elimination initiative of visceral leishmaniasis (VL) on the Indian subcontinent, one of the main questions remaining is whether asymptomatically infected individuals also contribute to transmission. We piloted a minimally invasive microbiopsy device that could help answer this question. While the potential of this device has been previously illustrated in Ethiopia, no such information is available for the setting of the Indian subcontinent. In this proof of concept study we aimed to assess 1) to what extent skin parasite load obtained with the new microbiopsy device correlates with disease status, 2) to what extent skin parasite load correlates with blood parasite load in the same subject, and 3) to what extent the skin parasite load obtained from different sampling sites on the body correlates with one another. Methods: We performed a pilot study in Bihar, India, including 29 VL patients, 28 PKDL patients, 94 asymptomatically infected individuals, 22 endemic controls (EC), and 28 non-endemic controls (NEC). Presence of infection with L. donovani in the blood was assessed using Direct Agglutination Test, rK39 ELISA, Whole Blood Analysis measuring IFN-γ and qPCR. A skin sample was collected with the microbiopsy device on two different locations on the body. PKDL patients provided a third skin sample from the edge of a PKDL lesion. Parasite load in the skin was measured by qPCR. Findings: We found a clear correlation between the skin parasite load obtained with the microbiopsy device and disease status, with both higher skin parasite loads and higher proportions of positive skin samples in VL and PKDL patients compared to asymptomatics, EC, and NEC. No clear correlation between skin parasite load and blood parasite load was found, but a moderate correlation was present between the skin parasite load in arm and neck samples. In addition, we found four positive skin samples among asymptomatic individuals, and 85% of PKDL lesions tested positive using this microbiopsy device. Conclusions: In line with previous pilot studies, our results from an Indian setting suggest that the microbiopsy device provides a promising tool to measure skin parasite load, and – if validated by xenodiagnosis studies – could facilitate much needed larger scale studies on infectiousness of human subgroups. In addition, we advocate further evaluation of this device as a diagnostic tool for PKDL. © Copyright © 2021 Cloots, Singh, Singh, Van der Auwera, Kumar, Gedda, Rai, Hasker, Sundar and Boelaert.
Human papillomavirus infection & anal cytological abnormalities in HIV-positive men in eastern India
(BioMed Central Ltd., 2018) Abhilasha Gautam; Jaya Chakravarty; Vijay Kumar Singh; Amrita Ghosh; Shashi Bhushan Chauhan; Madhukar Rai; Shyam Sundar
Background: Oncogenic Human papillomavirus (HPV) infections are closely associated with anal cancer which is high among human immunodeficiency virus (HIV) infected males. There are no data regarding anal HPV infection and cytological abnormalities in HIV positive males receiving free therapy in the national program. Thus, this cross-sectional study was performed to assess the prevalence and risk factors of anal HPV infection and cytological abnormalities in HIV positive males. Methods: We screened 126 HIV-positive male patients attending the antiretroviral treatment center (ART) between 2014 and 2015 with anal papanicolaou smear cytology and HPV-DNA testing. HPV-DNA was detected by using polymerase chain reaction (PCR) method with two consensus primer sets E6 and MY09/11 and further analyzed for the presence of various HPV genotype by Sanger sequencing. Risk factors associated with anal cytological abnormalities and HPV infection was analyzed by using univariate and multivariate logistic regression models. Results: Out of 126, 52 were on antiretroviral therapy. 91% were married to female partners but during the study 48 (38%) gave positive history of anal intercourse with other men. Anal cytology was done in 95 patients, out of which 60 (63.15%) had cytological abnormalities. LSIL (low-grade squamous intraepithelial lesions) was present in 27 (45%), ASCUS (atypical squamous cells of undetermined significance) in 31 (52%) and ASC-H (atypical squamous cells cannot exclude a high-grade squamous intraepithelial lesion) in 2 (3.33%). In multivariate analysis, the risk factors for cytological abnormality were presence of history of anal intercourse (OR, 6.1; 95% CI, 2.0-18.7) and WHO stage III & IV (OR, 2.7; 95% CI, 1.1-7.5). HPV-DNA was detected in 33/119 (27.73%) patients. The most prevalent HPV type in the study was HPV-16 (10.08%), other HPV types detected were 18,31,35,17,66,72,52,68 and 107 (17.65%). Conclusions: High prevalence of anal cytological abnormalities in our study suggests that regular anal Pap smear screening should be done in HIV positive males in the ART center. © 2018 The Author(s).
An Insight Into Systemic Immune Response in Leishmania donovani Mediated Atypical Cutaneous Leishmaniasis in the New Endemic State of Himachal Pradesh, India
(Frontiers Media S.A., 2022) Lovlesh Thakur; Priyanka Madaan; Aklank Jain; Vinay Shankar; Ajeet Negi; Shashi Bhushan Chauhan; Shyam Sundar; Om Prakash Singh; Manju Jain
Leishmaniasis continues to afflict known and newer endemic sites despite global efforts towards its control and elimination. In this regard, the emergence of newer endemic sites with unusual disease formats is recognized wherein Leishmania donovani complex classically known to cause visceral disease is demonstrated to cause cutaneous manifestation. In this context, atypical cutaneous leishmaniasis (CL) cases caused by L. donovani genetic variants from the newer endemic state of Himachal Pradesh (HP) in India are beginning to be understood in terms of parasite determinants. The atypical CL manifestation further needs to be explored to define host immune correlates with a possible role in driving the unusual disease progression. In the given study, we performed comprehensive systemic-immune profiling of the atypical CL patients from the study area in HP, India, in comparison with the classical visceral leishmaniasis (VL) patients from the northeast region of India. The systemic immune response was studied using ELISA-based assessment of Th1, Th2, Th17, Treg, and Th22 specific plasma cytokine expression pattern and parasite-specific total serum IgG/IgG subclasses. The specified immune correlates are known to exhibit heterogeneous association with the different infecting parasite species, infection load, and co-lateral host immunopathology in classical CL and VL. In the atypical CL patient group, altered expression of IL-10 emerged as the key finding that could potentially fine-tune the Th1/Th17/Th22 effector cytokine axis towards a localized cutaneous manifestation. A reduced expression of IL-10 along with a high IFN-γ/IL-10 ratio as a readout of effective parasite killing defined atypical cutaneous outcome. In contrast, high circulatory IL-10 levels and a depressed IFN-γ/IL-10 ratio were seen in classical VL patients in line with an ineffective parasite-killing cytokine response. Overall, the study highlights new knowledge on host immune correlates in terms of cytokine expression pattern and IgG subclasses that underline atypical disease manifestation such that L. donovani, a generally visceralizing parasite species cause skin localized cutaneous lesions. Copyright © 2022 Thakur, Madaan, Jain, Shankar, Negi, Chauhan, Sundar, Singh and Jain.
Short-course, cost-effective treatment with amphotericin B-fat emulsion cures visceral leishmaniasis
(Royal Society of Tropical Medicine and Hygiene, 2000) Shyam Sundar; Lal B. Gupta; Vishal Rastogi; Gaurav Agrawal; Henry W. Murray
Although short-course therapy with new lipid formulations of amphotericin B represents an advance over lengthy traditional treatments in visceral leishmaniasis (kala-azar), high cost has rendered these agents largely irrelevant in developing countries where the disease is endemic. Therefore, we tested standard amphotericin B deoxycholate mixed with a commercial fat emulsion as short-course treatment for Indian visceral leishmaniasis in Bihar in 1997/98. Seventy children and adults with splenic aspirate-documented infection, 23 of whom had failed prior antimony (Sb) therapy, received 5 alternate-day infusions of 2 mg/kg. Apparent cure, which required a parasite-free splenic aspirate smear, was assessed 20 days after treatment (day 30); definitive cure was determined at 6 months. Other than anticipated infusion-related fever and/or chills, treatment was safe and well tolerated. One patient required dose modification because of mild, reversible renal insufficiency. Sixty-nine patients (98.6%, CI 92.3-100%) had apparent cures; during follow-up, there were 4 treatment failures (relapses, 3; unrelated death, 1), yielding definitive cures in 65 of 70 patients (92.9%, CI 84.1-97.6%). Including retreatment costs for patients in Bihar (who now often fail initial Sb therapy), the final per patient cost of the tested regimen (US $260) was 59% and 43% less than treatment with Sb or conventional amphotericin B alone, respectively. Short-course treatment with amphotericin B-fat emulsion is active, cost-effective treatment for patients with visceral leishmaniasis including those with Sb-unresponsive infection.
Cure of antimony-unresponsive Indian post-kala-azar dermal leishmaniasis with oral miltefosine
(2006) Shyam Sundar; Kailash Kumar; Jaya Chakravarty; Dipti Agrawal; Shrinkhla Agrawal; Amit Chhabra; Vikram Singh
We report the case of a patient with Indian post-kala-azar dermal leishmaniasis (PKDL) who failed to show any response to 2 months' treatment with sodium stibogluconate. Six months later he was treated with oral miltefosine on a compassionate basis as an off-label indication. Miltefosine was given 100 mg daily in divided doses for an initial 8 weeks. Due to insufficient response, the treatment was extended up to a total of 12 weeks. The patient showed an excellent response to treatment, and after 12 months of follow-up there was complete healing of all cutaneous lesions. Oral miltefosine appears to be an important alternative for the treatment of PKDL in India and confirmatory studies in controlled clinical trials are needed. © 2005.
Factors associated with unexplained sudden deaths among adults aged 18-45 years in India – A multicentric matched case–control study
(Wolters Kluwer Medknow Publications, 2023) Manickam Ponnaiah; Tarun Bhatnagar; Rizwan Suliankachi Abdulkader; Rajalakshmi Elumalai; Janani Surya; Kathiresan Jeyashree; Muthusamy Santhosh Kumar; Ranjithkumar Govindaraju; Jeromie Wesley Vivian Thangaraj; Hari Krishan Aggarwal; Suresh Balan; Tridip Dutta Baruah; Ayan Basu; Yogita Bavaskar; Ajeet Singh Bhadoria; Ashish Bhalla; Pankaj Bhardwaj; Rachana Bhat; Jaya Chakravarty; Gina Maryann Chandy; Bal Kishan Gupta; Rakesh Kakkar; Ali Hasan Faiz Karnam; Sushila Kataria; Janakkumar Khambholja; Dewesh Kumar; Nithin Kumar; Monaliza Lyngdoh; M. Selva Meena; Kedar Mehta; M.P. Sheethal; Subhasis Mukherjee; Anuj Mundra; Arun Murugan; Seetharaman Narayanan; Balamurugan Nathan; Jutika Ojah; Pushpa Patil; Sunita Pawar; A. Charles Pon Ruban; R. Vadivelu; Rishabh Kumar Rana; S. Nagendra Boopathy; S. Priya; Saroj Kumar Sahoo; Arti Shah; Mohammad Shameem; Karthikeyan Shanmugam; Sachin K. Shivnitwar; Abhishek Singhai; Saurabh Srivastava; Sudheera Sulgante; Arunansu Talukdar; Alka Verma; Rajaat Vohra; Rabbanie Tariq Wani; Bhargavi Bathula; Gayathri Kumari; Divya Saravana Kumar; Aishwariya Narasimhan; N.C. Krupa; Thirumaran Senguttuvan; Parvathi Surendran; Dharsikaa Tamilmani; Alka Turuk; Gunjan Kumar; Aparna Murkherjee; Rakesh Aggarwal; Manoj Vasant Murhekar; Anjan Jyoti Talukdhar; Raj Prathim Das; Pranab Jyoti Bhattacharyya; Pankaj Jyoti Barman; Partha Pratim Das; P.V.M. Lakshmi; Naveen Panday; Ashok Kumar Pannu; Debaprasad Dhibar; Pankaj Kumar Kanauje; Satyajit Singh; Sabah Siddiqui; Nitin Bhajandas Borkar; Mayur Adalja; Sandip Shah Varsha Godbole; Rikin Raj; Nehal Shah; Nilay Suthar; Hemang Purohit; Bhargav Patel; Rutika Pathkjee; Niraj Pandit; Siddharth Shah; Bhavesh Patel; Anuja Agrawal; Deepak Jain; Manish Bansal; Vikas Deswal; Pooja Sharma; Farhana Siraj; Aamir Rashid; Anjum Bashir Fazili; Pradip Kumar Bhattacharya; Hirendra Birua; Manoj Kumar Prasad; Shashi Bhushan Singh; Umendra Kumar Ojha; Ravi Ranjan Jha; L.M. Manuja; S.K. Raghavendra; Vijay Hugar; R. Radha; Pallavi Kesari; Sunil Tapse; Ambrish Avate; Prasanna Kumar; Bhaskaran Unnikrishnan; T. Rekha; A. Basavaprabhu; Mithun Rao; Prithvishree Ravindra; Chythra R. Rao; Jayaraj Mymbilly Balakrishnan; Vikram Palimar; S. Ashwini; Bhavana Hiremath; Rajnikanth Malapur; Ankur Joshi; Manoj Nagar; Atul S. Keche; Arjun Lal Kakrani; Shubhangi Kanitkar; Srikanth Tripathy; Savita Mahajan; Akshada Shinde; Sunil Patil; Vijay Gaikwad; Ganesh Lokhande; Astha Ganeriwal; Ramesh Wasnik; Ashwini Kalantri; Dhiraj Bhandari; Preetam Salunkhe; Abhishek Raut; Star Pala; K.G. Lynrah; Nari Lyngdoh; Rajani Thabah; Manish Kapoor; Sadananda Barik; Chitta Ranjan Mohanty; Sonu Hangma Subba; Satyabrata Guru; Manu Ayyan; Sitanshu Sekhar Kar; Nanda Kishore Maroju; Naveen Kumar; Roselin Mohandas; Charulatha Tamilselvan; Saranya Rajaram; Ankita Kankaria; Moonis Mirza; Preeti Singh Dhoat; Jaspreet Shergill; Manoj Kumar Gupta; Akhil Dhanesh Goel; Amit Kumar Rohila; Durga Shankar Meena; Archana Paliwal; Niti Gahlot; Nikita Sharma; Harkesh Kumar; Dinesh Choudhary; Shyam Lal Meena; Dinesh Bhambhu; Jigyasa Gupta; G. Priya; Sonia Samuel; S. Bagyalakshmi; Sathish Kumar T; Aazmi Mohamed; G. Rathna Kumar; A. Rajesh; V. Rajendran; M. Soorya; P.N. Sridevi; A. Karthika; K. Santha Sheela Kumari; K. Sathish Kumar; Pavithra Gnanavel; Dasarathan Ramesh; Aravind Gunasekaran; R. Kaverikannan; Madhumitha Manohar; P. Sofia; R. Abishek; Jeevithan Shanmugam; Mohan Kumar; Aparnavi Periyasamy; Dhilipan Kumar; G. Selvarani; Thirukumaran Ramasamy; N. Suresh; Kannan Muthuraman Alagappan; Mathavasami Vijayageetha; Sudha Ramalingam; Petchiappan Velammal; Yamini Subramani; Lakshmi Marappa; Viswanathan Pandurangan; T.R. Muralidharan; M. Rajkumar; Senthil Murugan Ramasamy; Bodhare Trupti; Bharath Rajh; Duvuru Amareswar Reddy; Rashmi Upadhyay; Anurag Srivastava; Rakesh Gupta; Ranjan Bhattnagar; Manaswi Chaubey; Soumik Ghosh; Nilesh Kumar; Mohammad Azharuddin; Nafees A. Khan; Mohammad Aslam; Asad Mahmood; R.K. Singh; Priyank Yadav; Aditya Kapoor; Om Prakash Sanjeev; Shyam Sundar; Prasan Kumar Panda; Mukesh Bairwa; Mahendera Singh Gehlot; Pooja Bhadoria; Arup Chakravorty; Sarmistha Chakravorty; Arindam Ray; Aparup Dhua; Amitava Pal; Priyanka Ghosh; Yogiraj Roy; Sinjita Dutta; Subhro Samujjal Basu
Background & objectives: In view of anecdotal reports of sudden unexplained deaths in India’s apparently healthy young adults, linking to coronavirus disease 2019 (COVID-19) infection or vaccination, we determined the factors associated with such deaths in individuals aged 18-45 years through a multicentric matched case–control study. Methods: This study was conducted through participation of 47 tertiary care hospitals across India. Cases were apparently healthy individuals aged 18-45 years without any known co-morbidity, who suddenly (<24 h of hospitalization or seen apparently healthy 24 h before death) died of unexplained causes during 1st October 2021-31st March 2023. Four controls were included per case matched for age, gender and neighborhood. We interviewed/perused records to collect data on COVID-19 vaccination/infection and post-COVID-19 conditions, family history of sudden death, smoking, recreational drug use, alcohol frequency and binge drinking and vigorous-intensity physical activity two days before death/interviews. We developed regression models considering COVID-19 vaccination ≤42 days before outcome, any vaccine received anytime and vaccine doses to compute an adjusted matched odds ratio (aOR) with 95 per cent confidence interval (CI). Results: Seven hundred twenty nine cases and 2916 controls were included in the analysis. Receipt of at least one dose of COVID-19 vaccine lowered the odds [aOR (95% CI)] for unexplained sudden death [0.58 (0.37, 0.92)], whereas past COVID-19 hospitalization [3.8 (1.36, 10.61)], family history of sudden death [2.53 (1.52, 4.21)], binge drinking 48 h before death/interview [5.29 (2.57, 10.89)], use of recreational drug/substance [2.92 (1.1, 7.71)] and performing vigorous-intensity physical activity 48 h before death/interview [3.7 (1.36, 10.05)] were positively associated. Two doses lowered the odds of unexplained sudden death [0.51 (0.28, 0.91)], whereas single dose did not. Interpretation & conclusions: COVID-19 vaccination did not increase the risk of unexplained sudden death among young adults in India. Past COVID-19 hospitalization, family history of sudden death and certain lifestyle behaviors increased the likelihood of unexplained sudden death. © 2023 Indian Journal of Medical Research, published by Wolters Kluwer - Medknow for Director-General, Indian Council of Medical Research.
Domestic mammals as reservoirs for Leishmania donovani on the Indian subcontinent: Possibility and consequences on elimination
(John Wiley and Sons Inc, 2022) Anurag Kumar Kushwaha; Breanna M. Scorza; Om Prakash Singh; Edgar Rowton; Phillip Lawyer; Shyam Sundar; Christine A. Petersen
Leishmania donovani is the causative agent of historically anthroponotic visceral leishmaniasis (VL) on the Indian subcontinent (ISC). L. donovani is transmitted by the sand fly species Phlebotomus argentipes. Our collaborative group and others have shown that sand flies trapped outside in endemic villages have fed on cattle and dogs in addition to people. Domestic animals are reservoirs for L. donovani complex spp., particularly L. infantum, in other endemic areas. Multiple studies using quantitative PCR or serological detection methods have demonstrated that goats, cattle, rats and dogs were diagnostically positive for L. donovani infection or exposure in eastern Africa, Bangladesh, Nepal and India. There is a limited understanding of the extent to which L. donovani infection of domestic animals drives transmission to other animals or humans on the ISC. Evidence from other vector-borne disease elimination strategies indicated that emerging infections in domestic species hindered eradication. The predominant lesson learned from these other situations is that non-human reservoirs must be identified, controlled and/or prevented. Massive efforts are underway for VL elimination on the Indian subcontinent. Despite these herculean efforts, residual VL incidence persists. The spectre of an animal reservoir complicating elimination efforts haunts the final push towards full VL control. Better understanding of L. donovani transmission on the Indian subcontinent and rigorous consideration of how non-human reservoirs alter VL ecology are critical to sustain elimination goals. © 2021 Wiley-VCH GmbH.
Lay perceptions of kala-azar, mosquitoes and bed nets in Bihar, India
(2010) Rabindra N. Mishra; S.P. Singh; Veerle Vanlerberghe; Shyam Sundar; Marleen Boelaert; Pierre Lefèvre
Objective To describe the lay perception of kala-azar (KA) in an endemic area of Muzaffarpur District, Bihar, India: local names, symptoms, affected persons, perceived severity and modes of transmission, as well as perceived mosquito nuisance, modes of protection and use of bed nets. Methods We held 16 focus group discussions (FGD) in eight remote villages with altogether 157 participants in March 2008. Separate FGDs were held according to gender, socio-economic status (SES) and with key informants. Results Kala-azar is most commonly named pilahi. Poor people were said to be the most affected. Knowledge about symptoms was satisfactory. Fever and prolonged fever were the most stated symptoms. KA was perceived as a life-threatening disease with a heavy economic burden. Mosquito bites were perceived as the main mode of transmission but in lower socio-economic groups, non-vector-related explanations were also provided. The main modes of protection from mosquitoes mentioned were the use of fumes and bed nets. Season was the strongest factor influencing the use of bed nets and non-affordability for not owning them. Conclusions Although the sand fly is not recognised as the vector, the relatively good awareness of disease transmission by mosquitoes and the nuisance caused by their high density might be an entry point for adopting preventive measures to protect from mosquito bite and thereby indirectly preventing from KA. Educational campaigns targeted to the poorer segments of society are needed to enhance knowledge about KA, its mode of transmission, risks of getting infected and to increase bed net use. © 2010 Blackwell Publishing Ltd.
Diagnostic PCR with Leishmania donovani specificity using sequences from the variable region of kinetoplast minicircle DNA
(1999) Neeloo Singh; Martin D. Curran; Anil K. Rastogil; Derek Middleton; Shyam Sundar
Kala azar or visceral leishmaniasis, a parasitic disease caused by Leishmania donovani, is presently causing an epidemic in the eastern region of India. Diagnosis of kala azar is often complicated. We developed a pair of oligonucleotides suitable as primers from the variable region of a predominant sequence class of minicircles of L. donovani. These primers were used in a nonisotopic polymerase chain reaction and found to be highly specific for the parasites of L. donovani complex. Using these primers, amplification of L. donovani kinetoplast DNA minicircle from the peripheral blood of kala azar patients results in a product of 204 bp. The patient group was comprised of individuals from a highly endemic region of India. We feel that PCR could assess the efficacy of new leishmanicidal drugs under investigation in these patients. PCR could also predict response to therapy which would be useful for both clinical and research applications.

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