Journal Article > ResearchFull Text
Clin Infect Dis. 2015 June 30 (Issue 8)
Mahajan R, Das P, Isaakidis P, Sunyoto T, Sagili KD, et al.
Clin Infect Dis. 2015 June 30 (Issue 8)
There are considerable numbers of patients co-infected with Human Immunodeficiency Virus (HIV) and Visceral Leishmaniasis (VL) in the VL-endemic areas of Bihar, India. These patients are at higher risk of relapse and death, but there are still no evidence-based guidelines on how to treat them. In this study, we report on treatment outcomes of co-infected patients up to 18 months following treatment with a combination regimen.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2014 August 7; Volume 8 (Issue 8); e3053.; DOI:10.1371/journal.pntd.0003053
Burza S, Mahajan R, Singh A, van Griensven J, Pandey K, et al.
PLoS Negl Trop Dis. 2014 August 7; Volume 8 (Issue 8); e3053.; DOI:10.1371/journal.pntd.0003053
Visceral Leishmaniasis (VL; also known as kala-azar) is an ultimately fatal disease endemic in the Indian state of Bihar, while HIV/AIDS is an emerging disease in this region. A 2011 observational cohort study conducted in Bihar involving 55 VL/HIV co-infected patients treated with 20-25 mg/kg intravenous liposomal amphotericin B (AmBisome) estimated an 85.5% probability of survival and a 26.5% probability of VL relapse within 2 years. Here we report the long-term field outcomes of a larger cohort of co-infected patients treated with this regimen between 2007 and 2012.
Conference Material > Poster
Niykayo LF, Mahajan R, Sagrado MJ, Ajack YBP, Chol BT, et al.
MSF Paediatric Days 2024. 2024 May 3; DOI:10.57740/CO9XKuY
Conference Material > Abstract
Chandna A, PRIORITISE Study Group, Mahajan R, Gautam P, Mwandigha L, et al.
MSF Scientific Days International 2022. 2022 May 9; DOI:10.57740/hxy9-yk07
INTRODUCTION
In locations where few people have received Covid-19 vaccines, health systems remain vulnerable to spikes in SARS-CoV-2 infections. Triage tools, which could include biomarkers, to identify patients with moderate Covid-19 infection suitable for community-based management would be useful in the event of surges. In consultation with FIND (Geneva, Switzerland) we shortlisted seven biomarkers for evaluation, all measurable using point-of-care tests, and either currently available or in late-stage development.
METHODS
We prospectively recruited unvaccinated adults with laboratory-confirmed Covid-19 presenting to two hospitals in India with moderate symptoms, in order to develop and validate a clinical prediction model to rule-out progression to supplemental oxygen requirement. Moderate disease was defined as oxygen saturation (SpO2) ≥ 94% and respiratory rate < 30 breaths per minute (bpm), in the context of systemic symptoms (breathlessness or fever and chest pain, abdominal pain, diarrhoea, or severe myalgia). All patients had clinical observations and blood collected at presentation, and were followed up for 14 days for the primary outcome, defined as any of the following: SpO2 < 94%; respiratory rate > 30 bpm; SpO2/fraction of inspired oxygen (FiO2) < 400; or death. We specified a priori that each model would contain three easily ascertained clinical parameters (age, sex, and SpO2) and one of the seven biomarkers (C-reactive protein (CRP), D-dimer, interleukin-6 (IL-6), neutrophil-to-lymphocyte ratio (NLR), procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), or soluble urokinase plasminogen activator receptor (suPAR)), to ensure the models would be implementable in high patient-throughput, low-resource settings. We evaluated the models’ discrimination, calibration, and clinical utility in a held-out external temporal validation cohort.
ETHICS
Ethical approval was given by the ethics committees of AIIMS and CMC, India, the Oxford Tropical Research Ethics Committee, UK; and by the MSF Ethics Review Board.
ClinicalTrials.gov number, NCT04441372.
RESULTS
426 participants were recruited, of which 89 (21.0%) met the primary outcome. 257 participants comprised the development, and 166 the validation, cohorts. The three models containing NLR, suPAR, or IL-6 demonstrated promising discrimination (c-statistics: 0.72 to 0.74) and calibration (calibration slopes: 1.01 to 1.05) in the held-out validation cohort. Furthermore, they provided greater utility than a model containing the clinical parameters alone (c-statistic = 0.66; calibration slope = 0.68). The inclusion of either NLR or suPAR improved predictive performance such that the ratio of correctly to incorrectly discharged patients increased from 10:1 to 23:1 or 25:1 respectively. Including IL-6 resulted in a similar proportion (~21%) of correctly discharged patients as the clinical model, but without missing any patients requiring supplemental oxygen.
CONCLUSION
We present three clinical prediction models that could help clinicians identify patients with moderate Covid-19 suitable for community-based management. These models are readily implementable and, if validated, could be of particular relevance for resource-limited settings.
CONFLICTS OF INTEREST
None declared.
In locations where few people have received Covid-19 vaccines, health systems remain vulnerable to spikes in SARS-CoV-2 infections. Triage tools, which could include biomarkers, to identify patients with moderate Covid-19 infection suitable for community-based management would be useful in the event of surges. In consultation with FIND (Geneva, Switzerland) we shortlisted seven biomarkers for evaluation, all measurable using point-of-care tests, and either currently available or in late-stage development.
METHODS
We prospectively recruited unvaccinated adults with laboratory-confirmed Covid-19 presenting to two hospitals in India with moderate symptoms, in order to develop and validate a clinical prediction model to rule-out progression to supplemental oxygen requirement. Moderate disease was defined as oxygen saturation (SpO2) ≥ 94% and respiratory rate < 30 breaths per minute (bpm), in the context of systemic symptoms (breathlessness or fever and chest pain, abdominal pain, diarrhoea, or severe myalgia). All patients had clinical observations and blood collected at presentation, and were followed up for 14 days for the primary outcome, defined as any of the following: SpO2 < 94%; respiratory rate > 30 bpm; SpO2/fraction of inspired oxygen (FiO2) < 400; or death. We specified a priori that each model would contain three easily ascertained clinical parameters (age, sex, and SpO2) and one of the seven biomarkers (C-reactive protein (CRP), D-dimer, interleukin-6 (IL-6), neutrophil-to-lymphocyte ratio (NLR), procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), or soluble urokinase plasminogen activator receptor (suPAR)), to ensure the models would be implementable in high patient-throughput, low-resource settings. We evaluated the models’ discrimination, calibration, and clinical utility in a held-out external temporal validation cohort.
ETHICS
Ethical approval was given by the ethics committees of AIIMS and CMC, India, the Oxford Tropical Research Ethics Committee, UK; and by the MSF Ethics Review Board.
ClinicalTrials.gov number, NCT04441372.
RESULTS
426 participants were recruited, of which 89 (21.0%) met the primary outcome. 257 participants comprised the development, and 166 the validation, cohorts. The three models containing NLR, suPAR, or IL-6 demonstrated promising discrimination (c-statistics: 0.72 to 0.74) and calibration (calibration slopes: 1.01 to 1.05) in the held-out validation cohort. Furthermore, they provided greater utility than a model containing the clinical parameters alone (c-statistic = 0.66; calibration slope = 0.68). The inclusion of either NLR or suPAR improved predictive performance such that the ratio of correctly to incorrectly discharged patients increased from 10:1 to 23:1 or 25:1 respectively. Including IL-6 resulted in a similar proportion (~21%) of correctly discharged patients as the clinical model, but without missing any patients requiring supplemental oxygen.
CONCLUSION
We present three clinical prediction models that could help clinicians identify patients with moderate Covid-19 suitable for community-based management. These models are readily implementable and, if validated, could be of particular relevance for resource-limited settings.
CONFLICTS OF INTEREST
None declared.
Conference Material > Abstract
Nair MM, Kumar P, Mahajan R, Harshana A, Richardson K, et al.
MSF Scientific Days International 2020: Research. 2020 May 20
INTRODUCTION
Effective palliative care requires a multidisciplinary and holistic approach based on the provision of comprehensive care with treatment of pain and physical symptoms, management of psychosocial needs, as well as other non-medical needs. Few studies exist about palliative care in India, particularly in the context of people living with HIV/AIDS. MSF supports an advanced HIV inpatient ward in Bihar, where mortality rates are high. We aimed to explore the lived experiences of palliative care among patients, and their families, with advanced HIV, to understand conceptions of illness, death, and end-of-life care in Bihar, India.
METHODS
We carried out an exploratory, qualitative study using 21 semi-structured in-depth interviews and 1 focus group discussion. Participants included patients living with HIV/AIDS (PLHA), caregivers, relatives of deceased patients who had been treated in a government hospital, and key informants from community-based organizations in Patna, Bihar. Interview data were transcribed verbatim, translated from Hindi or other local languages into English by research assistants, and analysed using NVIVO (QSR International, Victoria, Australia). Two researchers then carried out inductive, thematic analysis of the data. Emergent codes and categories were identified and compared to subsequent areas of inquiry.
ETHICS
This study was approved by the ethics committee of the All India Institute of Medical Sciences, Patna, India, and the MSF Ethics Review Board.
RESULTS
Latent thematic analysis revealed poor understanding of palliative care among advanced HIV patients and their caregivers; the term “palliative care” was not known to PLHA. PLHA and relatives expected active treatment, despite poor prognosis, and believed that dying patients should be provided a separate, private inpatient area. However, patients were able to identify the importance of psychosocial counselling, the desire for a separate dedicated space for terminal patients with social and recreational activities to prevent isolation, and a preference for home-based palliative care wherever possible. Our data showed that relatives of patients played a substantial role in influencing doctors and nurses to avoid divulging the nature of the disease and prognosis directly to patients. There was variation in preferences for open disclosure of prognosis amongst critically ill PLHA and relatives of deceased patients.
CONCLUSION
There is a need to improve palliative care provision for advanced HIV patients in Bihar, who do not typically have access to such services. PLHA should have a separate dedicated area, with adequate psychosocial counselling for patients and families, and regular recreational activities to prevent social isolation.
CONFLICTS OF INTEREST
None declared.
Effective palliative care requires a multidisciplinary and holistic approach based on the provision of comprehensive care with treatment of pain and physical symptoms, management of psychosocial needs, as well as other non-medical needs. Few studies exist about palliative care in India, particularly in the context of people living with HIV/AIDS. MSF supports an advanced HIV inpatient ward in Bihar, where mortality rates are high. We aimed to explore the lived experiences of palliative care among patients, and their families, with advanced HIV, to understand conceptions of illness, death, and end-of-life care in Bihar, India.
METHODS
We carried out an exploratory, qualitative study using 21 semi-structured in-depth interviews and 1 focus group discussion. Participants included patients living with HIV/AIDS (PLHA), caregivers, relatives of deceased patients who had been treated in a government hospital, and key informants from community-based organizations in Patna, Bihar. Interview data were transcribed verbatim, translated from Hindi or other local languages into English by research assistants, and analysed using NVIVO (QSR International, Victoria, Australia). Two researchers then carried out inductive, thematic analysis of the data. Emergent codes and categories were identified and compared to subsequent areas of inquiry.
ETHICS
This study was approved by the ethics committee of the All India Institute of Medical Sciences, Patna, India, and the MSF Ethics Review Board.
RESULTS
Latent thematic analysis revealed poor understanding of palliative care among advanced HIV patients and their caregivers; the term “palliative care” was not known to PLHA. PLHA and relatives expected active treatment, despite poor prognosis, and believed that dying patients should be provided a separate, private inpatient area. However, patients were able to identify the importance of psychosocial counselling, the desire for a separate dedicated space for terminal patients with social and recreational activities to prevent isolation, and a preference for home-based palliative care wherever possible. Our data showed that relatives of patients played a substantial role in influencing doctors and nurses to avoid divulging the nature of the disease and prognosis directly to patients. There was variation in preferences for open disclosure of prognosis amongst critically ill PLHA and relatives of deceased patients.
CONCLUSION
There is a need to improve palliative care provision for advanced HIV patients in Bihar, who do not typically have access to such services. PLHA should have a separate dedicated area, with adequate psychosocial counselling for patients and families, and regular recreational activities to prevent social isolation.
CONFLICTS OF INTEREST
None declared.
Conference Material > Slide Presentation
Mahajan R, Owen SI, Kumar S, Kazmi S, Das P, et al.
MSF Scientific Days International 2021: Research. 2021 May 19
Conference Material > Abstract
Mahajan R, Owen SI, Kumar S, Kazmi S, Das P, et al.
MSF Scientific Days International 2021: Research. 2021 May 19
INTRODUCTION
People co-infected with visceral leishmaniasis and HIV (VL-HIV) typically present with advanced HIV disease and in poor clinical condition. The reasons for this are complex, but one major challenge relates to difficulties in ensuring early diagnosis of VL, a stage IV opportunistic infection, in the context of HIV. In VL-endemic areas, it is recognised that between 2 and 20% of the general population may harbour asymptomatic Leishmania infection (ALI), the vast majority of whom will not progress to symptomatic disease. However, similar data are absent for people living with HIV (PLHIV) in South Asia. Being able to diagnose ALI may provide a screen-and-treat opportunity to prevent progression to the fatal symptomatic form. We investigated the prevalence and determinants of ALI in PLHIV living in VL-endemic areas, and the risk of progression to symptomatic VL.
METHODS
We conducted a cross-sectional survey, enrolling PLHIV aged ≥18 with no diagnosis of or history of leishmaniasis symptoms, at three antiretroviral therapy centres within VL-endemic regions of Bihar, India. ALI was defined as a positive rK39 enzyme-linked immunosorbent assay (ELISA), rK39 rapid diagnostic test (RDT), and/or quantitative polymerase chain reaction (qPCR) result on blood. In addition, we tested for the Leishmania antigen in urine using ELISA as a novel non-invasive alternative. Participants were followed up at three-monthly intervals over 18 months to assess status and progression to symptomatic infection.
ETHICS
This study was approved by the ethics boards of the Rajendra Memorial Research Institute of Medical Sciences, Patna, India, and Liverpool School of Tropical Medicine, UK, and the MSF Ethics Review Board. Clinical Trial Registry-India number, CTRI/2017/03/008120.
RESULTS
1,296 PLHIV were included in the analysis. The baseline prevalence of ALI was 7.4% (n=96). All were found positive using rK39 ELISA, while 0.5% (n=6) and 0.4% (n=5) were positive using qPCR and rK39 RDT, respectively. 2.2% (n=28) patients were positive using urinary Leishmania antigen ELISA testing. Independent risk factors (p<0.05) for ALI were CD4 count <100 cells/mm3 (adjusted odds ratio, aOR, 3.1; 95%CI 1.2-7.6), and CD4 count between 100-199 cells/mm3 (aOR=2.1; 95%CI 1.1-4.0), as compared to CD4 ≥300 cells/mm3 and living in a household size ≥5 (aOR=1.8; 95%CI 1.1-3.2). Concordance between diagnostic tests was poor. A total of 109 asymptomatic patients were followed up prospectively, including 13 additional patients who were identified during pilot testing. Overall, 3.7% (n=4) patients converted from asymptomatic to symptomatic infection over the study period. Conversion rates of participants identified as positive using rK39 ELISA, rK39 RDT, qPCR, and urinary Leishmania antigen ELISA, were 3.7% (4/109), 40% (2/5), 57% (4/7), and 14% (4/29), respectively. Risk of all-cause mortality in those with ALI over 18 months’ follow-up was 6.4% (n=7), compared with 2.5% (n=30) in those without (risk ratio, 2.6, 95%CI 1.2-5.7, p=0.018).
CONCLUSION
PLHIV living in highly VL-endemic areas have a relatively high prevalence of ALI. Although progression rates to symptomatic infection appear low, all-cause mortality rates are higher and may reflect the impact of sub-clinical infection on HIV outcomes. The results may justify further studies investigating early treatment of ALI in PLHIV.
People co-infected with visceral leishmaniasis and HIV (VL-HIV) typically present with advanced HIV disease and in poor clinical condition. The reasons for this are complex, but one major challenge relates to difficulties in ensuring early diagnosis of VL, a stage IV opportunistic infection, in the context of HIV. In VL-endemic areas, it is recognised that between 2 and 20% of the general population may harbour asymptomatic Leishmania infection (ALI), the vast majority of whom will not progress to symptomatic disease. However, similar data are absent for people living with HIV (PLHIV) in South Asia. Being able to diagnose ALI may provide a screen-and-treat opportunity to prevent progression to the fatal symptomatic form. We investigated the prevalence and determinants of ALI in PLHIV living in VL-endemic areas, and the risk of progression to symptomatic VL.
METHODS
We conducted a cross-sectional survey, enrolling PLHIV aged ≥18 with no diagnosis of or history of leishmaniasis symptoms, at three antiretroviral therapy centres within VL-endemic regions of Bihar, India. ALI was defined as a positive rK39 enzyme-linked immunosorbent assay (ELISA), rK39 rapid diagnostic test (RDT), and/or quantitative polymerase chain reaction (qPCR) result on blood. In addition, we tested for the Leishmania antigen in urine using ELISA as a novel non-invasive alternative. Participants were followed up at three-monthly intervals over 18 months to assess status and progression to symptomatic infection.
ETHICS
This study was approved by the ethics boards of the Rajendra Memorial Research Institute of Medical Sciences, Patna, India, and Liverpool School of Tropical Medicine, UK, and the MSF Ethics Review Board. Clinical Trial Registry-India number, CTRI/2017/03/008120.
RESULTS
1,296 PLHIV were included in the analysis. The baseline prevalence of ALI was 7.4% (n=96). All were found positive using rK39 ELISA, while 0.5% (n=6) and 0.4% (n=5) were positive using qPCR and rK39 RDT, respectively. 2.2% (n=28) patients were positive using urinary Leishmania antigen ELISA testing. Independent risk factors (p<0.05) for ALI were CD4 count <100 cells/mm3 (adjusted odds ratio, aOR, 3.1; 95%CI 1.2-7.6), and CD4 count between 100-199 cells/mm3 (aOR=2.1; 95%CI 1.1-4.0), as compared to CD4 ≥300 cells/mm3 and living in a household size ≥5 (aOR=1.8; 95%CI 1.1-3.2). Concordance between diagnostic tests was poor. A total of 109 asymptomatic patients were followed up prospectively, including 13 additional patients who were identified during pilot testing. Overall, 3.7% (n=4) patients converted from asymptomatic to symptomatic infection over the study period. Conversion rates of participants identified as positive using rK39 ELISA, rK39 RDT, qPCR, and urinary Leishmania antigen ELISA, were 3.7% (4/109), 40% (2/5), 57% (4/7), and 14% (4/29), respectively. Risk of all-cause mortality in those with ALI over 18 months’ follow-up was 6.4% (n=7), compared with 2.5% (n=30) in those without (risk ratio, 2.6, 95%CI 1.2-5.7, p=0.018).
CONCLUSION
PLHIV living in highly VL-endemic areas have a relatively high prevalence of ALI. Although progression rates to symptomatic infection appear low, all-cause mortality rates are higher and may reflect the impact of sub-clinical infection on HIV outcomes. The results may justify further studies investigating early treatment of ALI in PLHIV.
Journal Article > ResearchFull Text
Clin Infect Dis. 2014 May 10; Volume 59 (Issue 4); 552-555.; DOI:10.1093/cid/ciu333
Burza S, Mahajan R, Sanz MG, Sunyoto T, Kumar R, et al.
Clin Infect Dis. 2014 May 10; Volume 59 (Issue 4); 552-555.; DOI:10.1093/cid/ciu333
Although human immunodeficiency virus (HIV) and visceral leishmaniasis coinfection is recognized as a major public health challenge in Africa, data regarding the prevalence in India are very limited. Consecutive HIV screening of 2077 patients aged ≥14 years with confirmed visceral leishmaniasis in Bihar, eastern India, found that 5.6% were HIV positive, including 2.4% with newly diagnosed HIV infection.
Conference Material > Poster
Moreto-Planas L, Mahajan R, Sagrado MJ, Flevaud L, Gallo J, et al.
MSF Scientific Day International 2023. 2023 June 7; DOI:10.57740/0xmg-7p42
Journal Article > ResearchFull Text
PLOS One. 2019 July 27; Volume 14; DOI:10.1371/journal.pone.0219002
Nair MM, Tripathi S, Mazumdar S, Mahajan R, Harshana A, et al.
PLOS One. 2019 July 27; Volume 14; DOI:10.1371/journal.pone.0219002
Background
Misuse of antibiotics is a well-known driver of antibiotic resistance. Given the decentralized model of the Indian health system and the shortage of allopathic doctors in rural areas, a wide variety of healthcare providers cater to the needs of patients in urban and rural settings. This qualitative study explores the drivers of antibiotic use among formal and informal healthcare providers as well as patients accessing care at primary health centers across Paschim Bardhaman district in West Bengal.
Materials and methods
We conducted 28 semi-structured, in-depth interviews with four groups of healthcare providers (allopathic doctors, informal health providers, nurses, and pharmacy shopkeepers) as well as patients accessing care at primary health centers and hospitals across Paschim Bardhaman district. Qualitative data was analyzed using the framework method in an inductive and deductive manner.
Results
Our results indicate that patients demand antibiotics from healthcare providers and seek the fastest cure possible, which influences the prescription choices of healthcare providers, particularly informal health providers. Many allopathic doctors provide antibiotics without any clinical indication due to inconsistent follow up, lack of testing facilities, risk of secondary infections, and unhygienic living conditions. Pharmaceutical company representatives actively network with informal health providers and formal healthcare providers alike, and regularly visit providers even in remote areas to market newer antibiotics. Allopathic doctors and informal health providers frequently blame the other party for being responsible for antibiotic resistance, and yet both display interdependence in referring patients to one another.
Conclusions
A holistic approach to curbing antibiotic resistance in West Bengal and other parts of India should focus on strengthening the capacity of the existing public health system to deliver on its promises, improving patient education and counseling, and including informal providers and pharmaceutical company representatives in community-level antibiotic stewardship efforts.
Misuse of antibiotics is a well-known driver of antibiotic resistance. Given the decentralized model of the Indian health system and the shortage of allopathic doctors in rural areas, a wide variety of healthcare providers cater to the needs of patients in urban and rural settings. This qualitative study explores the drivers of antibiotic use among formal and informal healthcare providers as well as patients accessing care at primary health centers across Paschim Bardhaman district in West Bengal.
Materials and methods
We conducted 28 semi-structured, in-depth interviews with four groups of healthcare providers (allopathic doctors, informal health providers, nurses, and pharmacy shopkeepers) as well as patients accessing care at primary health centers and hospitals across Paschim Bardhaman district. Qualitative data was analyzed using the framework method in an inductive and deductive manner.
Results
Our results indicate that patients demand antibiotics from healthcare providers and seek the fastest cure possible, which influences the prescription choices of healthcare providers, particularly informal health providers. Many allopathic doctors provide antibiotics without any clinical indication due to inconsistent follow up, lack of testing facilities, risk of secondary infections, and unhygienic living conditions. Pharmaceutical company representatives actively network with informal health providers and formal healthcare providers alike, and regularly visit providers even in remote areas to market newer antibiotics. Allopathic doctors and informal health providers frequently blame the other party for being responsible for antibiotic resistance, and yet both display interdependence in referring patients to one another.
Conclusions
A holistic approach to curbing antibiotic resistance in West Bengal and other parts of India should focus on strengthening the capacity of the existing public health system to deliver on its promises, improving patient education and counseling, and including informal providers and pharmaceutical company representatives in community-level antibiotic stewardship efforts.