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.
Journal Article > CommentaryFull Text
J Glob Antimicrob Resist. 2021 October 22; Volume 27; 236-238.; DOI:10.1016/j.jgar.2021.10.007
Nair MM, Zeegers MP, Varghese GM, Burza S
J Glob Antimicrob Resist. 2021 October 22; Volume 27; 236-238.; DOI:10.1016/j.jgar.2021.10.007
Antimicrobial resistance (AMR) is widely recognised as a global health threat, which is projected to account for more deaths than cancer by 2050. The Government of India has formulated a National Action Plan to tackle AMR (NAP-AMR), largely modelled on the World Health Organization's Global Action Plan on AMR. While the NAP-AMR successfully mirrors the Global Action Plan and lays out ambitious goals, we find that the lack of financial allocation across states, poor enforcement and inadequate multisectoral co-ordination have hampered progress. A broader focus on improving infrastructure for water and sanitation, linking the issue of AMR to existing vertical health programmes for human immunodeficiency virus (HIV) and tuberculosis (TB), prioritising infection prevention and control, strengthening the frontline healthcare workforce in rural and peri-urban settings to reduce reliance on antibiotics, leveraging point-of-care testing and mobile app-based health interventions for diagnosis and surveillance, and adopting a socioecological approach to health and development would help to create an enabling environment for concrete action on AMR in India.
Conference Material > Abstract
Hadiuzzaman M, Yantzi R, van den Boogaard W, Lim SY, Gupta PS, et al.
MSF Scientific Days International 2022. 2022 May 12; DOI:10.57740/2hjs-zc19
INTRODUCTION
Maternal health indicators remain unacceptably poor within the densely populated Rohingya refugee camps in Cox’s Bazar, Bangladesh. With a high prevalence of home births, we sought to explore perceptions, experiences, and expectations around delivery care of women of reproductive age. We also examined the potential roles of family and key community members within Camp 22, a relatively isolated camp with 23,000 refugees where MSF is the only provider of facility-based maternity care.
METHODS
In 2021, we selected 45 participants from Camp 22 through purposive and snowball sampling for in-depth interviews. Participants included 36 Rohingya women and their family members, three traditional birth attendants (TBA’s) and six community and religious leaders. Interviews were recorded, translated and transcribed into English by trained staff fluent in Rohingya. Thematic-content analysis was performed, whereby codes and emerging themes were identified.
ETHICS
This study was approved by the MSF Ethics Review Board (ERB) and by the ERB of Bangladesh University of Health Sciences.
RESULTS
Findings showed that delivery choices were made as a family, with husband and parents-in-law being primary decision makers. An uncomplicated birth was not perceived as requiring facility-based assistance; many women preferred to give birth at home assisted by TBA’s, family, or local healers, due to placing greater trust in their own community. Lack of security and transport were crucial determinants in repudiating facility-based care at night. Concerns about male staff and being undressed during facility-based births, as well as the possibility of onward referrals should surgery or episiotomies be required, drove hesitancy. Separation from family and children added more anxiety. Lack of understanding by facility staff towards Rohingya birthing practices and beliefs, and the Rohingya’s unfamiliarity with formally-trained midwives and medical procedures, featured heavily in decisions for home births. Factors such as utilising birthing ropes and guaranteed privacy at home were key influencers for choosing home births. Additionally, perceived inexperience of midwives and lack of autonomy while in the facility, were other common reasons for apprehension.
CONCLUSION
This study emphasizes community trust as a factor in collective decision-making regarding birth choices. Trust was higher in TBA’s than in formally-trained midwives and this negatively affected perceptions regarding competence. Perceptions may also be affected by rapid midwife turnover, a factor endemic to non-governmental organizations working in Cox’s Bazar. The persistent gap in cultural understanding and adaptation by facility-based staff, even after three years of presence, suggests the need for a more iterative, inclusive and reflective approach, with community engagement strategies founded on beneficiaries own explicitly stated needs, beliefs and practices.
CONFLICTS OF INTEREST
None declared
Maternal health indicators remain unacceptably poor within the densely populated Rohingya refugee camps in Cox’s Bazar, Bangladesh. With a high prevalence of home births, we sought to explore perceptions, experiences, and expectations around delivery care of women of reproductive age. We also examined the potential roles of family and key community members within Camp 22, a relatively isolated camp with 23,000 refugees where MSF is the only provider of facility-based maternity care.
METHODS
In 2021, we selected 45 participants from Camp 22 through purposive and snowball sampling for in-depth interviews. Participants included 36 Rohingya women and their family members, three traditional birth attendants (TBA’s) and six community and religious leaders. Interviews were recorded, translated and transcribed into English by trained staff fluent in Rohingya. Thematic-content analysis was performed, whereby codes and emerging themes were identified.
ETHICS
This study was approved by the MSF Ethics Review Board (ERB) and by the ERB of Bangladesh University of Health Sciences.
RESULTS
Findings showed that delivery choices were made as a family, with husband and parents-in-law being primary decision makers. An uncomplicated birth was not perceived as requiring facility-based assistance; many women preferred to give birth at home assisted by TBA’s, family, or local healers, due to placing greater trust in their own community. Lack of security and transport were crucial determinants in repudiating facility-based care at night. Concerns about male staff and being undressed during facility-based births, as well as the possibility of onward referrals should surgery or episiotomies be required, drove hesitancy. Separation from family and children added more anxiety. Lack of understanding by facility staff towards Rohingya birthing practices and beliefs, and the Rohingya’s unfamiliarity with formally-trained midwives and medical procedures, featured heavily in decisions for home births. Factors such as utilising birthing ropes and guaranteed privacy at home were key influencers for choosing home births. Additionally, perceived inexperience of midwives and lack of autonomy while in the facility, were other common reasons for apprehension.
CONCLUSION
This study emphasizes community trust as a factor in collective decision-making regarding birth choices. Trust was higher in TBA’s than in formally-trained midwives and this negatively affected perceptions regarding competence. Perceptions may also be affected by rapid midwife turnover, a factor endemic to non-governmental organizations working in Cox’s Bazar. The persistent gap in cultural understanding and adaptation by facility-based staff, even after three years of presence, suggests the need for a more iterative, inclusive and reflective approach, with community engagement strategies founded on beneficiaries own explicitly stated needs, beliefs and practices.
CONFLICTS OF INTEREST
None declared
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 > Poster
Kumar V, Murali S, Goldberg J, Alonso B, Moretó-Planas L, et al.
MSF Scientific Days Asia. 2024 November 8
Journal Article > ResearchFull Text
Confl Health. 2021 December 20; Volume 15 (Issue 1); 93.; DOI:10.1186/s13031-021-00424-y
Boete C, Burza S, Lasry E, Moriana S, Robertson W
Confl Health. 2021 December 20; Volume 15 (Issue 1); 93.; DOI:10.1186/s13031-021-00424-y
BACKGROUND
The use and implementation of novel tools for malaria control such as long lasting impregnated bednets (LLINs) and Indoor Residual Spraying (IRS) over the last decade has contributed to a substantial reduction in malaria burden globally. However numerous challenges exist particularly in relation to vector control in emergency settings. This study seeks to explore expert opinion on the utility of existing tools within the emergency context setting and to better understand the attitude towards emerging and innovative tools (including Genetically Modified Mosquitoes) to augment current approaches.
METHODS
80 experts in the field of malaria and vector control were invited to participate in a two-round Delphi survey. They were selected through a combination of literature (academic and policy publications) review and snowball sampling reflecting a range of relevant backgrounds including vector control experts, malaria programme managers and emergency response specialists. The survey was conducted online through a questionnaire including the possibility for free text entry, and concentrated on the following topics: 1. Utility and sustainability of current vector control tools, both in and outside emergency settings 2. Feasibility, utility and challenges of emerging vector control tools, both in and outside emergency settings 3. Current and unmet research priorities in malaria vector control and in malaria control in general.
RESULTS
37 experts completed the first round and 31 completed the second round of the survey. There was a stronger consensus about the increased utility of LLIN compared to IRS in all settings, while insecticide-treated covers and blankets ranked very high only in emergency settings. When considering the combination of tools, the ones deemed most interesting always involved LLINs and IRS regardless of the setting, and the acceptability and the efficacy at reducing transmission are essential characteristics. Regarding perceptions of tools currently under development, consensus was towards improvement of existing tools rather than investing in novel approaches and the majority of respondents expressed distrust for genetic approaches.
CONCLUSION
Malaria vector control experts expressed more confidence for tools whose efficacy is backed up by epidemiological evidence, hence a preference for the improvement rather than the combination of existing tools. Moreover, while several novel tools are under development, the majority of innovative approaches did not receive support, particularly in emergency settings. Stakeholders involved in the development of novel tools should involve earlier and raise awareness of the potential effectiveness amongst a wider range of experts within the malaria community to increase acceptability and improve early adoption once the evidence base is established.
The use and implementation of novel tools for malaria control such as long lasting impregnated bednets (LLINs) and Indoor Residual Spraying (IRS) over the last decade has contributed to a substantial reduction in malaria burden globally. However numerous challenges exist particularly in relation to vector control in emergency settings. This study seeks to explore expert opinion on the utility of existing tools within the emergency context setting and to better understand the attitude towards emerging and innovative tools (including Genetically Modified Mosquitoes) to augment current approaches.
METHODS
80 experts in the field of malaria and vector control were invited to participate in a two-round Delphi survey. They were selected through a combination of literature (academic and policy publications) review and snowball sampling reflecting a range of relevant backgrounds including vector control experts, malaria programme managers and emergency response specialists. The survey was conducted online through a questionnaire including the possibility for free text entry, and concentrated on the following topics: 1. Utility and sustainability of current vector control tools, both in and outside emergency settings 2. Feasibility, utility and challenges of emerging vector control tools, both in and outside emergency settings 3. Current and unmet research priorities in malaria vector control and in malaria control in general.
RESULTS
37 experts completed the first round and 31 completed the second round of the survey. There was a stronger consensus about the increased utility of LLIN compared to IRS in all settings, while insecticide-treated covers and blankets ranked very high only in emergency settings. When considering the combination of tools, the ones deemed most interesting always involved LLINs and IRS regardless of the setting, and the acceptability and the efficacy at reducing transmission are essential characteristics. Regarding perceptions of tools currently under development, consensus was towards improvement of existing tools rather than investing in novel approaches and the majority of respondents expressed distrust for genetic approaches.
CONCLUSION
Malaria vector control experts expressed more confidence for tools whose efficacy is backed up by epidemiological evidence, hence a preference for the improvement rather than the combination of existing tools. Moreover, while several novel tools are under development, the majority of innovative approaches did not receive support, particularly in emergency settings. Stakeholders involved in the development of novel tools should involve earlier and raise awareness of the potential effectiveness amongst a wider range of experts within the malaria community to increase acceptability and improve early adoption once the evidence base is established.
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.