Journal Article > ResearchFull Text
BMJ Glob Health. 2022 December 1; Volume 7 (Issue 12); e009674.; DOI:10.1136/bmjgh-2022-009674
Van Bortel W, Mariën J, Jacobs BKM, Sinzinkayo D, Sinarinzi P, et al.
BMJ Glob Health. 2022 December 1; Volume 7 (Issue 12); e009674.; DOI:10.1136/bmjgh-2022-009674
BACKGROUND
Long-lasting insecticidal nets (LLINs) are one of the key interventions in the global fight against malaria. Since 2014, mass distribution campaigns of LLINs aim for universal access by all citizens of Burundi. In this context, we assess the impact of LLINs mass distribution campaigns on malaria incidence, focusing on the endemic highland health districts. We also explored the possible correlation between observed trends in malaria incidence with any variations in climate conditions.
METHODS
Malaria cases for 2011—2019 were obtained from the National Health Information System. We developed a generalised additive model based on a time series of routinely collected data with malaria incidence as the response variable and timing of LLIN distribution as an explanatory variable to investigate the duration and magnitude of the LLIN effect on malaria incidence. We added a seasonal and continuous-time component as further explanatory variables, and health district as a random effect to account for random natural variation in malaria cases between districts.
RESULTS
Malaria transmission in Burundian highlands was clearly seasonal and increased non-linearly over the study period. Further, a fast and steep decline of malaria incidence was noted during the first year after mass LLIN distribution (p<0.0001). In years 2 and 3 after distribution, malaria cases started to rise again to levels higher than before the control intervention.
CONCLUSION
This study highlights that LLINs did reduce the incidence in the first year after a mass distribution campaign, but in the context of Burundi, LLINs lost their impact after only 1 year.
Long-lasting insecticidal nets (LLINs) are one of the key interventions in the global fight against malaria. Since 2014, mass distribution campaigns of LLINs aim for universal access by all citizens of Burundi. In this context, we assess the impact of LLINs mass distribution campaigns on malaria incidence, focusing on the endemic highland health districts. We also explored the possible correlation between observed trends in malaria incidence with any variations in climate conditions.
METHODS
Malaria cases for 2011—2019 were obtained from the National Health Information System. We developed a generalised additive model based on a time series of routinely collected data with malaria incidence as the response variable and timing of LLIN distribution as an explanatory variable to investigate the duration and magnitude of the LLIN effect on malaria incidence. We added a seasonal and continuous-time component as further explanatory variables, and health district as a random effect to account for random natural variation in malaria cases between districts.
RESULTS
Malaria transmission in Burundian highlands was clearly seasonal and increased non-linearly over the study period. Further, a fast and steep decline of malaria incidence was noted during the first year after mass LLIN distribution (p<0.0001). In years 2 and 3 after distribution, malaria cases started to rise again to levels higher than before the control intervention.
CONCLUSION
This study highlights that LLINs did reduce the incidence in the first year after a mass distribution campaign, but in the context of Burundi, LLINs lost their impact after only 1 year.
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.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2016 September 14; Volume 10 (Issue 9); DOI:10.1371/journal.pntd.0004880
Wassuna M, Njenga SN, Balasegaram M, Alexander N, Omollo R, et al.
PLoS Negl Trop Dis. 2016 September 14; Volume 10 (Issue 9); DOI:10.1371/journal.pntd.0004880
SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2019 February 21; DOI:10.1371/journal.pntd.0007132.
Diro EGJ, Edwards T, Ritmeijer KKD, Fikre H, Abongomera C, et al.
PLoS Negl Trop Dis. 2019 February 21; DOI:10.1371/journal.pntd.0007132.
BACKGROUND:
The long-term treatment outcome of visceral leishmaniasis (VL) patients with HIV co-infection is complicated by a high rate of relapse, especially when the CD4 count is low. Although use of secondary prophylaxis is recommended, it is not routinely practiced and data on its effectiveness and safety are limited.
METHODS:
A prospective cohort study was conducted in Northwest Ethiopia from August 2014 to August 2017 (NCT02011958). HIV-VL patients were followed for up to 12 months. Patients with CD4 cell counts below 200/μL at the end of VL treatment received pentamidine prophylaxis starting one month after parasitological cure, while those with CD4 count ≥200 cells/μL were followed without secondary prophylaxis. Compliance, safety and relapse-free survival, using Kaplan-Meier analysis methods to account for variable time at risk, were summarised. Risk factors for relapse or death were analysed.
RESULTS:
Fifty-four HIV patients were followed. The probability of relapse-free survival at one year was 50% (95% confidence interval [CI]: 35-63%): 53% (30-71%) in 22 patients with CD4 ≥200 cells/μL without pentamidine prophylaxis and 46% (26-63%) in 29 with CD4 <200 cells/μL who started pentamidine. Three patients with CD4 <200 cells/μL did not start pentamidine. Amongst those with CD4 ≥200 cells/μL, VL relapse was an independent risk factor for subsequent relapse or death (adjusted rate ratio: 5.42, 95% CI: 1.1-25.8). Except for one case of renal failure which was considered possibly related to pentamidine, there were no drug-related safety concerns.
CONCLUSION:
The relapse-free survival rate for VL patients with HIV was low. Relapse-free survival of patients with CD4 count <200cells/μL given pentamidine secondary prophylaxis appeared to be comparable to patients with a CD4 count ≥200 cells/μL not given prophylaxis. Patients with relapsed VL are at higher risk for subsequent relapse and should be considered a priority for secondary prophylaxis, irrespective of their CD4 count.
The long-term treatment outcome of visceral leishmaniasis (VL) patients with HIV co-infection is complicated by a high rate of relapse, especially when the CD4 count is low. Although use of secondary prophylaxis is recommended, it is not routinely practiced and data on its effectiveness and safety are limited.
METHODS:
A prospective cohort study was conducted in Northwest Ethiopia from August 2014 to August 2017 (NCT02011958). HIV-VL patients were followed for up to 12 months. Patients with CD4 cell counts below 200/μL at the end of VL treatment received pentamidine prophylaxis starting one month after parasitological cure, while those with CD4 count ≥200 cells/μL were followed without secondary prophylaxis. Compliance, safety and relapse-free survival, using Kaplan-Meier analysis methods to account for variable time at risk, were summarised. Risk factors for relapse or death were analysed.
RESULTS:
Fifty-four HIV patients were followed. The probability of relapse-free survival at one year was 50% (95% confidence interval [CI]: 35-63%): 53% (30-71%) in 22 patients with CD4 ≥200 cells/μL without pentamidine prophylaxis and 46% (26-63%) in 29 with CD4 <200 cells/μL who started pentamidine. Three patients with CD4 <200 cells/μL did not start pentamidine. Amongst those with CD4 ≥200 cells/μL, VL relapse was an independent risk factor for subsequent relapse or death (adjusted rate ratio: 5.42, 95% CI: 1.1-25.8). Except for one case of renal failure which was considered possibly related to pentamidine, there were no drug-related safety concerns.
CONCLUSION:
The relapse-free survival rate for VL patients with HIV was low. Relapse-free survival of patients with CD4 count <200cells/μL given pentamidine secondary prophylaxis appeared to be comparable to patients with a CD4 count ≥200 cells/μL not given prophylaxis. Patients with relapsed VL are at higher risk for subsequent relapse and should be considered a priority for secondary prophylaxis, irrespective of their CD4 count.
Protocol > Research Study
Hailu ADE, Diro EGJ, Kolja S, Ritmeijer KKD, Yifru S, et al.
2018 July 1
General Objectives
The overall objective of this trial is to identify a safe and effective treatment for VL in HIV coinfected
patients.
Primary Objective:
To evaluate at day 29 assessment the efficacy of a combination regimen of AmBisome®
+
miltefosine and AmBisome®
monotherapy in Ethiopian co-infected HIV + VL patients.
Secondary Objectives:
1. To evaluate relapse-free survival at day 390 (after initial cure at day 29 or cure at day 58 after
extended treatment).
2. To assess safety of the regimens.
Other objectives:
1.To evaluate of viral load and CD4 count in all patients
2. To evaluate the pharmacokinetics of ARV, Ambisome and miltefosine and immune function
markers in a subset of patients
The overall objective of this trial is to identify a safe and effective treatment for VL in HIV coinfected
patients.
Primary Objective:
To evaluate at day 29 assessment the efficacy of a combination regimen of AmBisome®
+
miltefosine and AmBisome®
monotherapy in Ethiopian co-infected HIV + VL patients.
Secondary Objectives:
1. To evaluate relapse-free survival at day 390 (after initial cure at day 29 or cure at day 58 after
extended treatment).
2. To assess safety of the regimens.
Other objectives:
1.To evaluate of viral load and CD4 count in all patients
2. To evaluate the pharmacokinetics of ARV, Ambisome and miltefosine and immune function
markers in a subset of patients
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2019 January 17; Volume 13 (Issue 1); DOI:10.1371/journal.pntd.0006988
Diro EGJ, Blesson S, Edwards T, Koert R, Ritmeijer KKD, et al.
PLoS Negl Trop Dis. 2019 January 17; Volume 13 (Issue 1); DOI:10.1371/journal.pntd.0006988
BACKGROUND
Visceral leishmaniasis (VL) in human immunodeficiency virus (HIV) co-infected patients requires special case management. AmBisome monotherapy at 40 mg/kg is recommended by the World Health Organization. The objective of the study was to assess if a combination of a lower dose of AmBisome with miltefosine would show acceptable efficacy at the end of treatment.
METHODOLOGY/PRINCIPAL FINDINGS
An open-label, non-comparative randomized trial of AmBisome (30 mg/kg) with miltefosine (100 mg/day for 28 days), and AmBisome monotherapy (40 mg/kg) was conducted in Ethiopian VL patients co-infected with HIV (NCT02011958). A sequential design was used with a triangular continuation region. The primary outcome was parasite clearance at day 29, after the first round of treatment. Patients with clinical improvement but without parasite clearance at day 29 received a second round of the allocated treatment. Efficacy was evaluated again at day 58, after completion of treatment.
Recruitment was stopped after inclusion of 19 and 39 patients in monotherapy and combination arms respectively, as per pre-specified stopping rules. At D29, intention-to-treat efficacy in the AmBisome arm was 70% (95% CI 45–87%) in the unadjusted analysis, and 50% (95% CI 27–73%) in the adjusted analysis, while in the combination arm, it was 81% (95% CI 67–90%) and 67% (95% CI 48–82%) respectively. At D58, the adjusted efficacy was 55% (95% CI 32–78%) in the monotherapy arm, and 88% (95% CI 79–98%) in the combination arm.
No major safety concerns related to the study medication were identified. Ten SAEs were observed within the treatment period, and 4 deaths unrelated to the study medication.
CONCLUSIONS/SIGNIFICANCE
The extended treatment strategy with the combination regimen showed the highest documented efficacy in HIV-VL patients; these results support a recommendation of this regimen as first-line treatment strategy for HIV-VL patients in eastern Africa.
TRIAL REGISTRATION NUMBER
www.clinicaltrials.gov NCT02011958
Visceral leishmaniasis (VL) in human immunodeficiency virus (HIV) co-infected patients requires special case management. AmBisome monotherapy at 40 mg/kg is recommended by the World Health Organization. The objective of the study was to assess if a combination of a lower dose of AmBisome with miltefosine would show acceptable efficacy at the end of treatment.
METHODOLOGY/PRINCIPAL FINDINGS
An open-label, non-comparative randomized trial of AmBisome (30 mg/kg) with miltefosine (100 mg/day for 28 days), and AmBisome monotherapy (40 mg/kg) was conducted in Ethiopian VL patients co-infected with HIV (NCT02011958). A sequential design was used with a triangular continuation region. The primary outcome was parasite clearance at day 29, after the first round of treatment. Patients with clinical improvement but without parasite clearance at day 29 received a second round of the allocated treatment. Efficacy was evaluated again at day 58, after completion of treatment.
Recruitment was stopped after inclusion of 19 and 39 patients in monotherapy and combination arms respectively, as per pre-specified stopping rules. At D29, intention-to-treat efficacy in the AmBisome arm was 70% (95% CI 45–87%) in the unadjusted analysis, and 50% (95% CI 27–73%) in the adjusted analysis, while in the combination arm, it was 81% (95% CI 67–90%) and 67% (95% CI 48–82%) respectively. At D58, the adjusted efficacy was 55% (95% CI 32–78%) in the monotherapy arm, and 88% (95% CI 79–98%) in the combination arm.
No major safety concerns related to the study medication were identified. Ten SAEs were observed within the treatment period, and 4 deaths unrelated to the study medication.
CONCLUSIONS/SIGNIFICANCE
The extended treatment strategy with the combination regimen showed the highest documented efficacy in HIV-VL patients; these results support a recommendation of this regimen as first-line treatment strategy for HIV-VL patients in eastern Africa.
TRIAL REGISTRATION NUMBER
www.clinicaltrials.gov NCT02011958