Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2018 May 25; Volume 12 (Issue 5); DOI:10.1371/journal.pntd.0006527
Abongomera C, Diro EGJ, de Lima Pereira A, Buyze J, Stille K, et al.
PLoS Negl Trop Dis. 2018 May 25; Volume 12 (Issue 5); DOI:10.1371/journal.pntd.0006527
North-west Ethiopia faces the highest burden world-wide of visceral leishmaniasis (VL) and HIV co-infection. VL-HIV co-infected patients have higher (initial) parasitological failure and relapse rates than HIV-negative VL patients. Whereas secondary prophylaxis reduces the relapse rate, parasitological failure rates remain high with the available antileishmanial drugs, especially when administered as monotherapy. We aimed to determine the initial effectiveness (parasitologically-confirmed cure) of a combination of liposomal amphotericin B (AmBisome) and miltefosine for treatment of VL in HIV co-infected patients.
Journal Article > ResearchAbstract Only
J Vector Borne Dis. 2021 July 1; DOI:10.4103/0972-9062.321747
Mahajan R, Nair MM, Saldanha AM, Harshana A, de Lima Pereira A, et al.
J Vector Borne Dis. 2021 July 1; DOI:10.4103/0972-9062.321747
BACKGROUND AND OBJECTIVES
There is limited evidence regarding the accuracy of dengue rapid diagnostic kits despite their extensive use in India. We evaluated the performance of four immunochromatographic Rapid Diagnostic Test (RDTs) kits: Multisure dengue Ab/Ag rapid test (MP biomedicals; MP), Dengucheck combo (Zephyr Biomedicals; ZB), SD bioline dengue duo (Alere; SD) and Dengue day 1 test (J Mitra; JM).
METHODS
This is a laboratory-based diagnostic evaluation study. Rapid tests results were compared to reference non-structural (NS1) antigen or immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) results of 241 dengue-positive samples and 247 dengue-negative samples. Sensitivity and specificity of NS1 and IgM components of each RDT were calculated separately and in combination (either NS1 or IgM positive) against reference standard ELISA.
RESULTS
A total of 238, 226, 208, and 146 reference NS1 ELISA samples were tested with MP, ZB, SD, and JM tests, respectively. In comparison to the NS1 ELISA reference tests, the NS1 component of MP, ZB, SD, and JM RDTs demonstrated a sensitivity of 71.8%, 85.1%, 77.2% and 80.9% respectively and specificity of 90.1%, 92.8%, 96.1 %, and 93.6%, respectively. In comparison to the IgM ELISA reference test, the IgM component of RDTs showed a sensitivity of 40.0%, 50.3%, 47.3% and 20.0% respectively and specificity of 92.4%, 88.6%, 96.5%, and 92.2% respectively. Combining NS1 antigen and IgM antibody results led to sensitivities of 87.5%, 82.9%, 93.8% and 91.7% respectively, and specificities of 75.3%, 73.9%, 76.5%, and 80.0% respectively.
INTERPRETATION & CONCLUSIONS
Though specificities were acceptable, the sensitivities of each test were markedly lower than manufacturers' claims. These results also support the added value of combined antigen-and antibody-based RDTs for the diagnosis of acute dengue.
There is limited evidence regarding the accuracy of dengue rapid diagnostic kits despite their extensive use in India. We evaluated the performance of four immunochromatographic Rapid Diagnostic Test (RDTs) kits: Multisure dengue Ab/Ag rapid test (MP biomedicals; MP), Dengucheck combo (Zephyr Biomedicals; ZB), SD bioline dengue duo (Alere; SD) and Dengue day 1 test (J Mitra; JM).
METHODS
This is a laboratory-based diagnostic evaluation study. Rapid tests results were compared to reference non-structural (NS1) antigen or immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) results of 241 dengue-positive samples and 247 dengue-negative samples. Sensitivity and specificity of NS1 and IgM components of each RDT were calculated separately and in combination (either NS1 or IgM positive) against reference standard ELISA.
RESULTS
A total of 238, 226, 208, and 146 reference NS1 ELISA samples were tested with MP, ZB, SD, and JM tests, respectively. In comparison to the NS1 ELISA reference tests, the NS1 component of MP, ZB, SD, and JM RDTs demonstrated a sensitivity of 71.8%, 85.1%, 77.2% and 80.9% respectively and specificity of 90.1%, 92.8%, 96.1 %, and 93.6%, respectively. In comparison to the IgM ELISA reference test, the IgM component of RDTs showed a sensitivity of 40.0%, 50.3%, 47.3% and 20.0% respectively and specificity of 92.4%, 88.6%, 96.5%, and 92.2% respectively. Combining NS1 antigen and IgM antibody results led to sensitivities of 87.5%, 82.9%, 93.8% and 91.7% respectively, and specificities of 75.3%, 73.9%, 76.5%, and 80.0% respectively.
INTERPRETATION & CONCLUSIONS
Though specificities were acceptable, the sensitivities of each test were markedly lower than manufacturers' claims. These results also support the added value of combined antigen-and antibody-based RDTs for the diagnosis of acute dengue.
Conference Material > Abstract
de Lima Pereira A, Saldanha E, Nair MM, Potter L, Bryson LHM
MSF Scientific Days International 2021: Innovation. 2021 May 20
WHAT CHALLENGES OR OPPORTUNITY DID YOU TRY TO ADDRESS? WERE EXISTING SOLUTIONS NOT AVAILABLE OR NOT GOOD ENOUGH?
An estimated 1.5 million children die each year from vaccine-preventable diseases. Besides vaccines, other life-saving drugs such as oxytocin, rectal artesunate, snake antivenom, insulin, and diazepam are unavailable at peripheral health centres due to a lack of cold chain facilities. Existing solutions are inadequate as they rely heavily on passive cold chain especially for the last mile, necessitating centralised models of healthcare delivery and leading to increased patient costs and limited access.
WHY DOES THIS CHALLENGE OR OPPORTUNITY MATTER--WHY SHOULD MSF ADDRESS IT?
Desk research has shown that there is no single product that can address this gap. A solution would have a positive impact at scale in most complex medical emergencies and could be a ubiquitous tool for decreasing mortality in neglected populations.
DESCRIBE YOUR INNOVATION AND WHAT MAKES IT INNOVATIVE
We are rethinking the passive vaccine day carrier by developing FriGO, a long-term, portable, active cool box that uses off-grid sources of energy. FriGo utilises solar power, thermoelectric cooling, phase-change material, battery back-up and a unique construction to provide continuous portable off-grid cooling for prolonged periods of time. FriGo benefits from accurate condition logging and monitoring and preventive action warning system. The technology that is utilised in FriGo has been individually proven in several other industries from international food shipping to outdoor camping. However, resource-limited healthcare settings require appropriately customised solutions. Although a handful of organisations are looking at this problem, a successful scalable solution is yet to be reached. The Covid-19 pandemic has brought a renewed focus on the vaccine cold chain industry and could act as a catalyst in bringing about this much needed change.
WHO WILL BENEFIT (WHOSE LIFE / WORK WILL IT IMPROVE?) AND WERE THEY INVOLVED IN THE DESIGN?
FriGo has the potential to decrease mortality and morbidity in most contexts where MSF works by increasing our reach and decreasing wastage.
WHAT OBJECTIVES DID YOU SET FOR THE PROJECT--WHAT DID YOU WANT TO ACHIEVE AND HOW DID YOU DEFINE AND MEASURE SUCCESS (IMPROVED SERVICE, LOWER COST, BETTER EFFICIENCY, BETTER USER EXPERIENCE, ETC.)?
In October 2019, we conducted a user preference study involving field workers and technical specialists to define and design the project. The primary objective and measure of success was to prove that a portable chamber could maintain a temperature of 2-8°C for a minimum of 28 days without an external energy source.
WHAT DATA DID YOU COLLECT TO MEASURE THE INNOVATION AGAINST THESE INDICATORS AND HOW DID YOU COLLECT IT? INCLUDE IF YOU DECIDED TO CHANGE THE INDICATORS AND WHY
Three assessments (desk research, technical study, and user preference study) were conducted to assess available products, feasibility, minimum requirements, cost comparison, and unmet needs. A proof-of-concept is underway.
HOW DID YOU ANALYSE THIS DATA TO UNDERSTAND TO WHAT EXTENT THE INNOVATION ACHIEVED ITS OBJECTIVES? DID THIS INCLUDE A COMPARISON TO THE STATUS QUO OR AN EXISTING SOLUTION?
Phase 1 aimed at validating the use-cases and reviewing the available products in the market. The data was collected through interviews and correspondence with experts and analysed by the team. The objectives for phase 2 were to validate the specific design and features, through an in-depth interview-based user preference study and a desk research technology analysis. Phase 3 objectives focus on validating the feasibility of the concept by building a proof-of-concept to demonstrate the proposed features of the product. The experimentation and testing are ongoing and will be assessed based on milestones established at the outset of the phase. The final milestone will be the ability to maintain a cold-life of 2-8°C for seven days with the possibility of continuous repeatability, without user-intervention or grid resources.
WERE THERE ANY LIMITATIONS TO THE DATA YOU COLLECTED, HOW YOU COLLECTED IT OR HOW YOU ANALYSED IT, OR WERE THERE ANY UNFORESEEN FACTORS THAT MAY HAVE INTERFERED WITH YOUR RESULTS?
Data collection was comprehensive, but non-exhaustive. Prototype data collection is underway but will need to be done in a range of field locations to ensure it works under various field conditions.
WHAT RESULTS DID YOU GET?
Phase 1 revealed that existing solutions, while some of them innovative, did not address all the current problems highlighted by some of the use-cases, and did not greatly change the current possibilities. The outcome of the user-preference study and technology analysis (phase 2) highlighted specific requirements such as being durable, easily carried on the back, suitable for all modes of transport, plug and play operation, and preferably around 2.5L in capacity. From a service perspective, the product needs to have prolonged cold life, minimal expertise and intervention, no grid dependency, non-circular route possibilities, fail-safe responses and decentralised operation. FriGo is being designed, prototyped and tested based on these findings. Some of the results achieved include the ability to cool a 1L payload chamber to 2-8°C, with an ambient temperature of +30°C, in under 4 hours solely using solar power, a thermoelectric heat pump, and a phase-change material thermal battery; with a current cold-life retention of 28h through an insulating structure.
COMPARING THE RESULTS FROM YOUR DATA ANALYSIS TO YOUR OBJECTIVES, EXPLAIN WHY YOU CONSIDER YOUR INNOVATION A SUCCESS OR FAILURE?
These conclusions can only be drawn after field testing is completed.
TO WHAT EXTENT DID THE INNOVATION BENEFIT PEOPLE’S LIVES / WORK?
This will be determined during the next phase of development, when FriGo is scaled-up and piloted.
IS THERE ANYTHING THAT YOU WOULD DO DIFFERENTLY IF YOU WERE TO DO THE WORK AGAIN?
Framing the product lifecycle to anticipate partnerships and legal processes, and consider alternative pathways, would reduce negative impacts on progress and timeline.
WHAT ARE THE NEXT STEPS FOR THE INNOVATION ITSELF (SCALE UP, IMPLEMENTATION, FURTHER DEVELOPMENT, DISCONTINUED)?
Following a successful proof-of-concept, we will build and distribute prototypes for field testing, ideally in collaboration with a commercialisation partner.
IS THE INNOVATION TRANSFERABLE OR ADAPTABLE TO OTHER SETTINGS OR DOMAINS?
Besides humanitarian settings, FriGo can be used in other medical contexts (including developed countries), farming and other cold chain dependent industries, and in end-consumer applications such as food and beverage storage.
WHAT BROADER IMPLICATIONS ARE THERE FROM THE INNOVATION FOR MSF AND / OR OTHERS (CHANGE IN PRACTICE, CHANGE IN POLICY, CHANGE IN GUIDELINES, PARADIGM SHIFT)?
If successful and cost efficient, FriGo could change the way MSF works by expanding reach for vaccination campaigns, allowing for decentralised healthcare delivery, and enabling home-based care in remote or conflict settings.
WHAT OTHER LEARNINGS FROM YOUR WORK ARE IMPORTANT TO SHARE?
MSF would benefit from an innovation culture backed by standard operating procedures for product development aspects such as partnerships, intellectual property, commercialisation, and mentorship.
ETHICS
This innovation project did not involve human participants or their data; the MSF Ethics Framework for Innovation was used to help identify and mitigate potential harms.
An estimated 1.5 million children die each year from vaccine-preventable diseases. Besides vaccines, other life-saving drugs such as oxytocin, rectal artesunate, snake antivenom, insulin, and diazepam are unavailable at peripheral health centres due to a lack of cold chain facilities. Existing solutions are inadequate as they rely heavily on passive cold chain especially for the last mile, necessitating centralised models of healthcare delivery and leading to increased patient costs and limited access.
WHY DOES THIS CHALLENGE OR OPPORTUNITY MATTER--WHY SHOULD MSF ADDRESS IT?
Desk research has shown that there is no single product that can address this gap. A solution would have a positive impact at scale in most complex medical emergencies and could be a ubiquitous tool for decreasing mortality in neglected populations.
DESCRIBE YOUR INNOVATION AND WHAT MAKES IT INNOVATIVE
We are rethinking the passive vaccine day carrier by developing FriGO, a long-term, portable, active cool box that uses off-grid sources of energy. FriGo utilises solar power, thermoelectric cooling, phase-change material, battery back-up and a unique construction to provide continuous portable off-grid cooling for prolonged periods of time. FriGo benefits from accurate condition logging and monitoring and preventive action warning system. The technology that is utilised in FriGo has been individually proven in several other industries from international food shipping to outdoor camping. However, resource-limited healthcare settings require appropriately customised solutions. Although a handful of organisations are looking at this problem, a successful scalable solution is yet to be reached. The Covid-19 pandemic has brought a renewed focus on the vaccine cold chain industry and could act as a catalyst in bringing about this much needed change.
WHO WILL BENEFIT (WHOSE LIFE / WORK WILL IT IMPROVE?) AND WERE THEY INVOLVED IN THE DESIGN?
FriGo has the potential to decrease mortality and morbidity in most contexts where MSF works by increasing our reach and decreasing wastage.
WHAT OBJECTIVES DID YOU SET FOR THE PROJECT--WHAT DID YOU WANT TO ACHIEVE AND HOW DID YOU DEFINE AND MEASURE SUCCESS (IMPROVED SERVICE, LOWER COST, BETTER EFFICIENCY, BETTER USER EXPERIENCE, ETC.)?
In October 2019, we conducted a user preference study involving field workers and technical specialists to define and design the project. The primary objective and measure of success was to prove that a portable chamber could maintain a temperature of 2-8°C for a minimum of 28 days without an external energy source.
WHAT DATA DID YOU COLLECT TO MEASURE THE INNOVATION AGAINST THESE INDICATORS AND HOW DID YOU COLLECT IT? INCLUDE IF YOU DECIDED TO CHANGE THE INDICATORS AND WHY
Three assessments (desk research, technical study, and user preference study) were conducted to assess available products, feasibility, minimum requirements, cost comparison, and unmet needs. A proof-of-concept is underway.
HOW DID YOU ANALYSE THIS DATA TO UNDERSTAND TO WHAT EXTENT THE INNOVATION ACHIEVED ITS OBJECTIVES? DID THIS INCLUDE A COMPARISON TO THE STATUS QUO OR AN EXISTING SOLUTION?
Phase 1 aimed at validating the use-cases and reviewing the available products in the market. The data was collected through interviews and correspondence with experts and analysed by the team. The objectives for phase 2 were to validate the specific design and features, through an in-depth interview-based user preference study and a desk research technology analysis. Phase 3 objectives focus on validating the feasibility of the concept by building a proof-of-concept to demonstrate the proposed features of the product. The experimentation and testing are ongoing and will be assessed based on milestones established at the outset of the phase. The final milestone will be the ability to maintain a cold-life of 2-8°C for seven days with the possibility of continuous repeatability, without user-intervention or grid resources.
WERE THERE ANY LIMITATIONS TO THE DATA YOU COLLECTED, HOW YOU COLLECTED IT OR HOW YOU ANALYSED IT, OR WERE THERE ANY UNFORESEEN FACTORS THAT MAY HAVE INTERFERED WITH YOUR RESULTS?
Data collection was comprehensive, but non-exhaustive. Prototype data collection is underway but will need to be done in a range of field locations to ensure it works under various field conditions.
WHAT RESULTS DID YOU GET?
Phase 1 revealed that existing solutions, while some of them innovative, did not address all the current problems highlighted by some of the use-cases, and did not greatly change the current possibilities. The outcome of the user-preference study and technology analysis (phase 2) highlighted specific requirements such as being durable, easily carried on the back, suitable for all modes of transport, plug and play operation, and preferably around 2.5L in capacity. From a service perspective, the product needs to have prolonged cold life, minimal expertise and intervention, no grid dependency, non-circular route possibilities, fail-safe responses and decentralised operation. FriGo is being designed, prototyped and tested based on these findings. Some of the results achieved include the ability to cool a 1L payload chamber to 2-8°C, with an ambient temperature of +30°C, in under 4 hours solely using solar power, a thermoelectric heat pump, and a phase-change material thermal battery; with a current cold-life retention of 28h through an insulating structure.
COMPARING THE RESULTS FROM YOUR DATA ANALYSIS TO YOUR OBJECTIVES, EXPLAIN WHY YOU CONSIDER YOUR INNOVATION A SUCCESS OR FAILURE?
These conclusions can only be drawn after field testing is completed.
TO WHAT EXTENT DID THE INNOVATION BENEFIT PEOPLE’S LIVES / WORK?
This will be determined during the next phase of development, when FriGo is scaled-up and piloted.
IS THERE ANYTHING THAT YOU WOULD DO DIFFERENTLY IF YOU WERE TO DO THE WORK AGAIN?
Framing the product lifecycle to anticipate partnerships and legal processes, and consider alternative pathways, would reduce negative impacts on progress and timeline.
WHAT ARE THE NEXT STEPS FOR THE INNOVATION ITSELF (SCALE UP, IMPLEMENTATION, FURTHER DEVELOPMENT, DISCONTINUED)?
Following a successful proof-of-concept, we will build and distribute prototypes for field testing, ideally in collaboration with a commercialisation partner.
IS THE INNOVATION TRANSFERABLE OR ADAPTABLE TO OTHER SETTINGS OR DOMAINS?
Besides humanitarian settings, FriGo can be used in other medical contexts (including developed countries), farming and other cold chain dependent industries, and in end-consumer applications such as food and beverage storage.
WHAT BROADER IMPLICATIONS ARE THERE FROM THE INNOVATION FOR MSF AND / OR OTHERS (CHANGE IN PRACTICE, CHANGE IN POLICY, CHANGE IN GUIDELINES, PARADIGM SHIFT)?
If successful and cost efficient, FriGo could change the way MSF works by expanding reach for vaccination campaigns, allowing for decentralised healthcare delivery, and enabling home-based care in remote or conflict settings.
WHAT OTHER LEARNINGS FROM YOUR WORK ARE IMPORTANT TO SHARE?
MSF would benefit from an innovation culture backed by standard operating procedures for product development aspects such as partnerships, intellectual property, commercialisation, and mentorship.
ETHICS
This innovation project did not involve human participants or their data; the MSF Ethics Framework for Innovation was used to help identify and mitigate potential harms.
Journal Article > ResearchFull Text
PLOS One. 2019 May 31; Volume 14 (Issue 5); DOI:10.1371/journal.pone.0217818
Nair MM, Tripathi S, Mazumdar S, Mahajan R, Harshana A, et al.
PLOS One. 2019 May 31; Volume 14 (Issue 5); DOI:10.1371/journal.pone.0217818
INTRODUCTION:
Antibiotic misuse is widespread and contributes to antibiotic resistance, especially in less regulated health systems such as India. Although informal providers are involved with substantial segments of primary healthcare, their level of knowledge, attitudes, and practices is not well documented in the literature.
OBJECTIVES:
This quantitative study systematically examines the knowledge, attitudes, and practices of informal and formal providers with respect to antibiotic use.
METHODS:
We surveyed a convenience sample of 384 participants (96 allopathic doctors, 96 nurses, 96 informal providers, and 96 pharmacy shopkeepers) over a period of 8 weeks from December to February using a validated questionnaire developed in Italy. Our team created an equivalent, composite KAP score for each respondent in the survey, which was subsequently compared between providers. We then performed a multivariate logistic regression analysis to estimate the odds of having a low composite score (<80) based on occupation by comparing allopathic doctors (referent category) with all other study participants. The model was adjusted for age (included as a continuous variable) and gender.
RESULTS:
Doctors scored highest in questions assessing knowledge (77.3%) and attitudes (87.3%), but performed poorly in practices (67.6%). Many doctors knew that antibiotics were not indicated for viral infections, but over 87% (n = 82) reported prescribing them in this situation. Nurses, pharmacy shopkeepers, and informal providers were more likely to perform poorly on the survey compared to allopathic doctors (OR: 10.4, 95% CI 5.4, 20.0, p<0.01). 30.8% (n = 118) of all providers relied on pharmaceutical company representatives as a major source of information about antibiotics.
CONCLUSIONS:
Our findings indicate poor knowledge and awareness of antibiotic use and functions among informal health providers, and dissonance between knowledge and practices among allopathic doctors. The nexus between allopathic doctors, pharmaceutical company representatives, and informal health providers present promising avenues for future research and intervention.
Antibiotic misuse is widespread and contributes to antibiotic resistance, especially in less regulated health systems such as India. Although informal providers are involved with substantial segments of primary healthcare, their level of knowledge, attitudes, and practices is not well documented in the literature.
OBJECTIVES:
This quantitative study systematically examines the knowledge, attitudes, and practices of informal and formal providers with respect to antibiotic use.
METHODS:
We surveyed a convenience sample of 384 participants (96 allopathic doctors, 96 nurses, 96 informal providers, and 96 pharmacy shopkeepers) over a period of 8 weeks from December to February using a validated questionnaire developed in Italy. Our team created an equivalent, composite KAP score for each respondent in the survey, which was subsequently compared between providers. We then performed a multivariate logistic regression analysis to estimate the odds of having a low composite score (<80) based on occupation by comparing allopathic doctors (referent category) with all other study participants. The model was adjusted for age (included as a continuous variable) and gender.
RESULTS:
Doctors scored highest in questions assessing knowledge (77.3%) and attitudes (87.3%), but performed poorly in practices (67.6%). Many doctors knew that antibiotics were not indicated for viral infections, but over 87% (n = 82) reported prescribing them in this situation. Nurses, pharmacy shopkeepers, and informal providers were more likely to perform poorly on the survey compared to allopathic doctors (OR: 10.4, 95% CI 5.4, 20.0, p<0.01). 30.8% (n = 118) of all providers relied on pharmaceutical company representatives as a major source of information about antibiotics.
CONCLUSIONS:
Our findings indicate poor knowledge and awareness of antibiotic use and functions among informal health providers, and dissonance between knowledge and practices among allopathic doctors. The nexus between allopathic doctors, pharmaceutical company representatives, and informal health providers present promising avenues for future research and intervention.
Journal Article > ResearchFull Text
Clin Infect Dis. 2022 October 15; 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. 2022 October 15; 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.
Conference Material > Slide Presentation
de Lima Pereira A, Saldanha E, Nair MM, Potter L, Bryson LHM
MSF Scientific Days International 2021: Innovation. 2021 May 20