Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 30 August 2022; Volume 16 (Issue 8); e0010718.; DOI:10.1371/journal.pntd.0010718
Mahajan R, Owen SI, Kumar S, Pandey K, Kazmi S, et al.
PLoS Negl Trop Dis. 30 August 2022; Volume 16 (Issue 8); e0010718.; DOI:10.1371/journal.pntd.0010718
People living with HIV (PLHIV) have an increased risk of developing visceral leishmaniasis (VL) and poor outcomes compared to HIV negative individuals. Here, we aim to establish the prevalence and determinants of asymptomatic Leishmania infection (ALI) in a cohort of PLHIV in Bihar, India. We hoped to evaluate optimal diagnostic algorithms to detect ALI in PLHIV. We conducted a cross-sectional survey of PLHIV ≥18 years of age with no history or current diagnosis of VL or post kala-azar dermal leishmaniasis (PKDL) at anti-retroviral therapy centres within VL endemic districts of Bihar. ALI was defined as a positive rK39 enzyme-linked immunosorbent assay (ELISA), rK39 rapid diagnostic test (RDT) and/or quantitative polymerase chain reaction (qPCR). Additionally, the urinary Leishmania antigen ELISA was evaluated. Determinants for ALI were established using logistic regression and agreement between diagnostic tests calculated using Cohen’s Kappa. A total of 1,296 PLHIV enrolled in HIV care, 694 (53.6%) of whom were female and a median age of 39 years (interquartile range 33–46), were included in the analysis. Baseline prevalence of ALI was 7.4% (n = 96). All 96 individuals were positive by rK39 ELISA, while 0.5% (n = 6) and 0.4% (n = 5) were positive by qPCR and rK39 RDT, respectively. Negligible or weak agreement was seen between assays. Independent risk factors for ALI were CD4 counts <100 (OR 3.1; 95% CI 1.2–7.6) and CD4 counts 100–199 (OR = 2.1;95% CI:1.1–4.0) compared to CD4 counts ≥300, and a household size ≥5 (OR = 1.9;95% CI:1.1–3.1). A total of 2.2% (n = 28) participants were positive by Leishmania antigen ELISA, detecting 20 additional participants to the asymptomatic cohort. Prevalence of ALI in PLHIV in VL endemic villages in Bihar was relatively high. Using the Leishmania antigen ELISA, prevalence increased to 9.0%. Patients with low CD4 counts and larger household size were found to have significantly higher risk of ALI.
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.
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
BMC Public Health. 11 April 2013; Volume 13 (Issue 1); DOI:10.1186/1471-2458-13-332
van den Bogaart E, Berkhout MMZ, Nour AB, Mens PF, Talha AA, et al.
BMC Public Health. 11 April 2013; Volume 13 (Issue 1); DOI:10.1186/1471-2458-13-332
In areas where visceral leishmaniasis (VL) and malaria are co-endemic, co-infections are common. Clinical implications range from potential diagnostic delay to increased disease-related morbidity, as compared to VL patients. Nevertheless, public awareness of the disease remains limited. In VL-endemic areas with unstable and seasonal malaria, vulnerability to the disease persists through all age-groups, suggesting that in these populations, malaria may easily co-occur with VL, with potentially severe clinical effects.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 10 April 2012; Volume 6 (Issue 4); DOI:10.1371/journal.pntd.0001617
van den Bogaart E, Berkhout MMZ, Adams ER, Mens PF, Sentongo E, et al.
PLoS Negl Trop Dis. 10 April 2012; Volume 6 (Issue 4); DOI:10.1371/journal.pntd.0001617
Due to geographic overlap of malaria and visceral leishmaniasis (VL), co-infections may exist but have been poorly investigated. To describe prevalence, features and risk factors for VL-malaria co-infections, a case-control analysis was conducted on data collected at Amudat Hospital, Uganda (2000-2006) by Médecins sans Frontières. Cases were identified as patients with laboratory-confirmed VL and malaria at hospital admission or during hospitalization; controls were VL patients with negative malaria smears. A logistic regression analysis was performed to study the association between patients' characteristics and the occurrence of the co-infection.