Conference Material > Poster
Maich G, Kumar N, Anuradha S, Pradhan GS, Verma N
MSF Scientific Days Asia. 8 November 2024
Journal Article > ResearchFull Text
Clin Infect Dis. 15 October 2022; Volume 75 (Issue 8); 1423-1432.; DOI:10.1093/cid/ciac127
Burza S, Mahajan R, Kazmi S, Alexander N, Kumar D, et al.
Clin Infect Dis. 15 October 2022; Volume 75 (Issue 8); 1423-1432.; DOI:10.1093/cid/ciac127
BACKGROUND
Visceral leishmaniasis (VL) in patients living with Human-Immunodeficiency-Virus (HIV) present an increasingly important patient cohort in areas where both infections are endemic. Evidence for treatment is sparce, with no high-quality studies from the Indian sub-continent.
METHODS
This is a randomised open label, parallel arm phase-3 trial conducted within a single hospital in Patna, India. 150 patients aged =18 years with serologically confirmed HIV and parasitologically confirmed VL were randomly allocated to one of two treatment arms, either a total 40mg/kg intravenous liposomal amphotericin B(AmBisome) administered in 8 equal doses over 24-days, or a total 30mg/kg intravenous liposomal amphotericin B(AmBisome) administered in 6 equal doses given concomitantly with a total 1.4g oral miltefosine administered through two daily doses of 50mg over 14-days. The primary outcome was ITT relapse-free-survival at day-210, defined as absence of signs and symptoms of VL, or if symptomatic negative parasitological investigations.
FINDINGS
Among 243 patients assessed for eligibility, 150 were recruited between 2nd January 2017 and 5th April 2018, with no loss-to-follow-up. Relapse free survival at day-210 was 85%, (64/75; 95%CI 77-100) in the monotherapy arm, and 96%, (72/75;95%CI 90-100) in the combination arm. 19%(28/150) were infected with concurrent tuberculosis, divided equally between arms. Excluding those with concurrent tuberculosis, relapse free survival at day-210 was 90%, (55/61;95%CI 82-100) in the monotherapy and 97%, (59/61;95%CI 91-100) in the combination therapy arm. Serious adverse events were uncommon and similar in each arm.
CONCLUSIONS
Combination therapy appears to be safe, well tolerated and effective, and halves treatment duration of current recommendations.
Visceral leishmaniasis (VL) in patients living with Human-Immunodeficiency-Virus (HIV) present an increasingly important patient cohort in areas where both infections are endemic. Evidence for treatment is sparce, with no high-quality studies from the Indian sub-continent.
METHODS
This is a randomised open label, parallel arm phase-3 trial conducted within a single hospital in Patna, India. 150 patients aged =18 years with serologically confirmed HIV and parasitologically confirmed VL were randomly allocated to one of two treatment arms, either a total 40mg/kg intravenous liposomal amphotericin B(AmBisome) administered in 8 equal doses over 24-days, or a total 30mg/kg intravenous liposomal amphotericin B(AmBisome) administered in 6 equal doses given concomitantly with a total 1.4g oral miltefosine administered through two daily doses of 50mg over 14-days. The primary outcome was ITT relapse-free-survival at day-210, defined as absence of signs and symptoms of VL, or if symptomatic negative parasitological investigations.
FINDINGS
Among 243 patients assessed for eligibility, 150 were recruited between 2nd January 2017 and 5th April 2018, with no loss-to-follow-up. Relapse free survival at day-210 was 85%, (64/75; 95%CI 77-100) in the monotherapy arm, and 96%, (72/75;95%CI 90-100) in the combination arm. 19%(28/150) were infected with concurrent tuberculosis, divided equally between arms. Excluding those with concurrent tuberculosis, relapse free survival at day-210 was 90%, (55/61;95%CI 82-100) in the monotherapy and 97%, (59/61;95%CI 91-100) in the combination therapy arm. Serious adverse events were uncommon and similar in each arm.
CONCLUSIONS
Combination therapy appears to be safe, well tolerated and effective, and halves treatment duration of current recommendations.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 7 August 2014; 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. 7 August 2014; 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 > Slide Presentation
Mahajan R, Owen SI, Kumar S, Kazmi S, Das P, et al.
MSF Scientific Days International 2021: Research. 19 May 2021
Conference Material > Abstract
Mahajan R, Owen SI, Kumar S, Kazmi S, Das P, et al.
MSF Scientific Days International 2021: Research. 19 May 2021
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
PLoS Negl Trop Dis. 2 January 2014; Volume 8 (Issue 1); e2603.; DOI:10.1371/journal.pntd.0002603
Burza S, Sinha PK, Mahajan R, Lima MA, Mitra G, et al.
PLoS Negl Trop Dis. 2 January 2014; Volume 8 (Issue 1); e2603.; DOI:10.1371/journal.pntd.0002603
Visceral Leishmaniasis (VL; also known as Kala-azar) is an ultimately fatal disease endemic in Bihar. A 2007 observational cohort study in Bihar of 251 patients with VL treated with 20 mg/Kg intravenous liposomal amphotericin B (Ambisome) demonstrated a 98% cure rate at 6-months. Between July 2007 and August 2012, Médecins Sans Frontières (MSF) and the Rajendra Memorial Research Institute (RMRI) implemented a VL treatment project in Bihar, India-an area highly endemic for Leishmania donovani-using this regimen as first-line treatment.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2 January 2014; Volume 8 (Issue 1); e2536.; DOI:10.1371/journal.pntd.0002536
Burza S, Sinha PK, Mahajan R, Lima MA, Mitra G, et al.
PLoS Negl Trop Dis. 2 January 2014; Volume 8 (Issue 1); e2536.; DOI:10.1371/journal.pntd.0002536
A proportion of all immunocompetent patients treated for visceral leishmaniasis (VL) are known to relapse; however, the risk factors for relapse are not well understood. With the support of the Rajendra Memorial Research Institute (RMRI), Médecins Sans Frontières (MSF) implemented a program in Bihar, India, using intravenous liposomal amphotericin B (Ambisome) as a first-line treatment for VL. The aim of this study was to identify risk factors for VL relapse by examining the characteristics of immunocompetent patients who relapsed following this regimen.
Protocol > Research Protocol
BMJ Open. 30 April 2021; Volume 11 (Issue 4); e042519.; DOI:10.1136/bmjopen-2020-042519
Owen SI, Burza S, Kumar S, Verma N, Mahajan R, et al.
BMJ Open. 30 April 2021; Volume 11 (Issue 4); e042519.; DOI:10.1136/bmjopen-2020-042519
INTRODUCTION
HIV coinfection presents a challenge for diagnosis of visceral leishmaniasis (VL). Invasive splenic or bone marrow aspiration with microscopic visualisation of Leishmania parasites remains the gold standard for diagnosis of VL in HIV-coinfected patients. Furthermore, a test of cure by splenic or bone marrow aspiration is required as patients with VL-HIV infection are at a high risk of treatment failure. However, there remain financial, implementation and safety costs to these invasive techniques which severely limit their use under field conditions.
METHODS AND ANALYSIS
We aim to evaluate blood and skin qPCR, peripheral blood buffy coat smear microscopy and urine antigen ELISA as non-invasive or minimally invasive alternatives for diagnosis and post-treatment test of cure for VL in HIV-coinfected patients in India, using a sample of 91 patients with parasitologically confirmed symptomatic VL-HIV infection.
HIV coinfection presents a challenge for diagnosis of visceral leishmaniasis (VL). Invasive splenic or bone marrow aspiration with microscopic visualisation of Leishmania parasites remains the gold standard for diagnosis of VL in HIV-coinfected patients. Furthermore, a test of cure by splenic or bone marrow aspiration is required as patients with VL-HIV infection are at a high risk of treatment failure. However, there remain financial, implementation and safety costs to these invasive techniques which severely limit their use under field conditions.
METHODS AND ANALYSIS
We aim to evaluate blood and skin qPCR, peripheral blood buffy coat smear microscopy and urine antigen ELISA as non-invasive or minimally invasive alternatives for diagnosis and post-treatment test of cure for VL in HIV-coinfected patients in India, using a sample of 91 patients with parasitologically confirmed symptomatic VL-HIV infection.
Journal Article > ResearchFull Text
Clin Infect Dis. 1 October 2011; Volume 53 (Issue 7); DOI:10.1093/cid/cir521
Sinha PK, van Griensven J, Pandey K, Kumar N, Verma N, et al.
Clin Infect Dis. 1 October 2011; Volume 53 (Issue 7); DOI:10.1093/cid/cir521
Reports on treatment outcomes of visceral leishmaniasis (VL)-human immunodeficiency virus (HIV) coinfection in India are lacking. To our knowledge, none have studied the efficacy of liposomal amphotericin B in VL-HIV coinfection. We report the 2-year treatment outcomes of VL-HIV-coinfected patients treated with liposomal amphotericin B followed by combination antiretroviral treatment (cART) in Bihar, India.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2 January 2014; Volume 8 (Issue 1); e2611.; DOI:10.1371/journal.pntd.0002611
Burza S, Sinha PK, Mahajan R, Gonzalez Sanz M, Lima MA, et al.
PLoS Negl Trop Dis. 2 January 2014; Volume 8 (Issue 1); e2611.; DOI:10.1371/journal.pntd.0002611
The skin disorder Post Kala-Azar Dermal Leishmaniasis (PKDL) occurs in up to 10% of patients treated for visceral leishmaniasis (VL) in India. The pathogenesis of PKDL is not yet fully understood. Cases have been reported in India following therapy with most available treatments, but rarely in those treated with liposomal amphotericin B (Ambisome). Between July 2007 and August 2012 with the support of the Rajendra Memorial Research Institute (RMRI), Médecins Sans Frontières (MSF) supported a VL treatment programme in Bihar, India-an area highly endemic for Leishmania donovani-in which 8749 patients received 20 mg/kg intravenous Ambisome as first-line treatment. This study describes the characteristics of patients who returned to the MSF supported treatment programme with PKDL.