Journal Article > CommentaryFull Text
Clin Infect Dis. 2015 August 10; Volume 62 (Issue 1); 69-74.; DOI:10.1093/cid/civ680
van Griensven J, De Weiggheleire A, Delamou A, Smith PJ, Edwards T, et al.
Clin Infect Dis. 2015 August 10; Volume 62 (Issue 1); 69-74.; DOI:10.1093/cid/civ680
The clinical evaluation of convalescent plasma (CP) for the treatment of Ebola Virus Disease (EVD) in the current outbreak, predominantly affecting Guinea, Sierra Leone and Liberia, was prioritized by the World Health Organization in September 2014. In each of these countries, non-randomized comparative clinical trials were initiated. The Ebola-Tx trial in Conakry, Guinea enrolled 102 patients by July 7, 2015; no severe adverse reactions were noted. The Ebola-CP trial in Sierra Leone and the EVD001 trial in Liberia have included few patients. While no efficacy data are available yet, current field experience supports the safety, acceptability and feasibility of CP as EVD treatment. Longer-term follow-up as well as data from non-trial settings and evidence on the scalability of the intervention are required. CP sourced from within the outbreak is the most readily available source of anti-EVD antibodies. Until the advent of effective antivirals or monoclonal antibodies, CP merits further evaluation.
Conference Material > Abstract
Mahajan R, Edwards T, Shandilya C, Kashyap V, Marino E, et al.
MSF Scientific Days International 2021: Research. 2021 May 19
INTRODUCTION
Limited data exist to inform community management of children with moderate acute malnutrition (MAM), who are normally excluded from severe acute malnutrition (SAM) treatment programmes. This study was conducted to generate evidence of longitudinal outcomes in children aged 6-59 months with MAM (defined as mid-upper arm circumference, MUAC, 115-124mm), without interventional supplementary feeding. In this study, children in India with MAM were followed up for six months to better understand their long-term nutritional outcomes.
METHODS
We carried out a multicentre prospective longitudinal observational study, nested within a randomized trial, in Jharkhand, India. Children with MAM were enrolled over a 12-month period in 46 centres in Jharkhand state, and followed up for six months while attending government integrated child development services. Anthropometric, clinical and sociodemographic characteristics were recorded at enrolment. The primary outcome was deterioration to SAM (MUAC <115 or bilateral pitting oedema) or death within six months. Risk factors for this outcome were investigated.
ETHICS
This study was approved by the MSF Ethical Review Board and by the ethics review boards of the Rajendra Institute of Medical Sciences, Ranchi and Jawaharlal Nehru University, New Delhi, India, and London School of Hygiene & Tropical Medicine, UK. Clinical Trial Registry-India number, CTRI/2017/12/010743.
RESULTS
Of 971 children enrolled, 98 (10.0%) were lost to follow-up, mainly linked with seasonal migration; 12 were seen outside of the six-month window (three before day 168 and nine after day 210). Of 861 children included in the analysis, 595 (61.3%) were female, with a mean age of 16.0 months (standard deviation 9.7). At enrolment 333 (34.3%) had MUAC 115-119mm, 430 (44.3%) had weight-for-height z-score (WHZ) <-3 and 431 (44%) had a WHZ of -2 to-3. Within six months, 133 (15.5%) deteriorated to SAM or died (95% confidence interval, CI: 13.1-18.0%; five deaths), of whom 97 children deteriorated to poor outcome (SAM or death) by three months (11.3%, with one death; representing over two thirds of those deteriorating to poor outcome by six months). In an adjusted logistic regression model, with an interaction between MUAC at enrolment (115-119, 120-124mm) and age (6-11, 12-23, ≥24 months), significantly increased odds of deterioration to SAM or death were seen amongst those with MUAC 115-119mm in all age groups (p≤0.02) and in those under one year with MUAC<125mm. After adjustment, there was no evidence of associations with socio-demographic factors, breastfeeding or WHZ<-3.
CONCLUSION
Children aged under 1 year and children with MUAC 115-119mm should be closely monitored, considering high MAM burdens in India. Increasing the MUAC admission criterion and/or targeted interventions for MAM children at higher risk could be considered. WHZ<-3 not already MUAC<115mm does not appear to be a risk factor for deterioration.
Limited data exist to inform community management of children with moderate acute malnutrition (MAM), who are normally excluded from severe acute malnutrition (SAM) treatment programmes. This study was conducted to generate evidence of longitudinal outcomes in children aged 6-59 months with MAM (defined as mid-upper arm circumference, MUAC, 115-124mm), without interventional supplementary feeding. In this study, children in India with MAM were followed up for six months to better understand their long-term nutritional outcomes.
METHODS
We carried out a multicentre prospective longitudinal observational study, nested within a randomized trial, in Jharkhand, India. Children with MAM were enrolled over a 12-month period in 46 centres in Jharkhand state, and followed up for six months while attending government integrated child development services. Anthropometric, clinical and sociodemographic characteristics were recorded at enrolment. The primary outcome was deterioration to SAM (MUAC <115 or bilateral pitting oedema) or death within six months. Risk factors for this outcome were investigated.
ETHICS
This study was approved by the MSF Ethical Review Board and by the ethics review boards of the Rajendra Institute of Medical Sciences, Ranchi and Jawaharlal Nehru University, New Delhi, India, and London School of Hygiene & Tropical Medicine, UK. Clinical Trial Registry-India number, CTRI/2017/12/010743.
RESULTS
Of 971 children enrolled, 98 (10.0%) were lost to follow-up, mainly linked with seasonal migration; 12 were seen outside of the six-month window (three before day 168 and nine after day 210). Of 861 children included in the analysis, 595 (61.3%) were female, with a mean age of 16.0 months (standard deviation 9.7). At enrolment 333 (34.3%) had MUAC 115-119mm, 430 (44.3%) had weight-for-height z-score (WHZ) <-3 and 431 (44%) had a WHZ of -2 to-3. Within six months, 133 (15.5%) deteriorated to SAM or died (95% confidence interval, CI: 13.1-18.0%; five deaths), of whom 97 children deteriorated to poor outcome (SAM or death) by three months (11.3%, with one death; representing over two thirds of those deteriorating to poor outcome by six months). In an adjusted logistic regression model, with an interaction between MUAC at enrolment (115-119, 120-124mm) and age (6-11, 12-23, ≥24 months), significantly increased odds of deterioration to SAM or death were seen amongst those with MUAC 115-119mm in all age groups (p≤0.02) and in those under one year with MUAC<125mm. After adjustment, there was no evidence of associations with socio-demographic factors, breastfeeding or WHZ<-3.
CONCLUSION
Children aged under 1 year and children with MUAC 115-119mm should be closely monitored, considering high MAM burdens in India. Increasing the MUAC admission criterion and/or targeted interventions for MAM children at higher risk could be considered. WHZ<-3 not already MUAC<115mm does not appear to be a risk factor for deterioration.
Journal Article > ResearchFull Text
N Engl J Med. 2016 January 7; Volume 374 (Issue 1); 33-42.; DOI:10.1056/NEJMoa1511812
van Griensven J, Edwards T, de Lamballerie X, Semple MG, Gallian P, et al.
N Engl J Med. 2016 January 7; Volume 374 (Issue 1); 33-42.; DOI:10.1056/NEJMoa1511812
BACKGROUND
In the wake of the recent outbreak of Ebola virus disease (EVD) in several African countries, the World Health Organization prioritized the evaluation of treatment with convalescent plasma derived from patients who have recovered from the disease. We evaluated the safety and efficacy of convalescent plasma for the treatment of EVD in Guinea.
METHODS
In this nonrandomized, comparative study, 99 patients of various ages (including pregnant women) with confirmed EVD received two consecutive transfusions of 200 to 250 ml of ABO-compatible convalescent plasma, with each unit of plasma obtained from a separate convalescent donor. The transfusions were initiated on the day of diagnosis or up to 2 days later. The level of neutralizing antibodies against Ebola virus in the plasma was unknown at the time of administration. The control group was 418 patients who had been treated at the same center during the previous 5 months. The primary outcome was the risk of death during the period from 3 to 16 days after diagnosis with adjustments for age and the baseline cycle-threshold value on polymerase-chain-reaction assay; patients who had died before day 3 were excluded. The clinically important difference was defined as an absolute reduction in mortality of 20 percentage points in the convalescent-plasma group as compared with the control group.
RESULTS
A total of 84 patients who were treated with plasma were included in the primary analysis. At baseline, the convalescent-plasma group had slightly higher cycle-threshold values and a shorter duration of symptoms than did the control group, along with a higher frequency of eye redness and difficulty in swallowing. From day 3 to day 16 after diagnosis, the risk of death was 31% in the convalescent-plasma group and 38% in the control group (risk difference, -7 percentage points; 95% confidence interval [CI], -18 to 4). The difference was reduced after adjustment for age and cycle-threshold value (adjusted risk difference, -3 percentage points; 95% CI, -13 to 8). No serious adverse reactions associated with the use of convalescent plasma were observed.
CONCLUSIONS
The transfusion of up to 500 ml of convalescent plasma with unknown levels of neutralizing antibodies in 84 patients with confirmed EVD was not associated with a significant improvement in survival. (Funded by the European Union's Horizon 2020 Research and Innovation Program and others; ClinicalTrials.gov number, NCT02342171.).
In the wake of the recent outbreak of Ebola virus disease (EVD) in several African countries, the World Health Organization prioritized the evaluation of treatment with convalescent plasma derived from patients who have recovered from the disease. We evaluated the safety and efficacy of convalescent plasma for the treatment of EVD in Guinea.
METHODS
In this nonrandomized, comparative study, 99 patients of various ages (including pregnant women) with confirmed EVD received two consecutive transfusions of 200 to 250 ml of ABO-compatible convalescent plasma, with each unit of plasma obtained from a separate convalescent donor. The transfusions were initiated on the day of diagnosis or up to 2 days later. The level of neutralizing antibodies against Ebola virus in the plasma was unknown at the time of administration. The control group was 418 patients who had been treated at the same center during the previous 5 months. The primary outcome was the risk of death during the period from 3 to 16 days after diagnosis with adjustments for age and the baseline cycle-threshold value on polymerase-chain-reaction assay; patients who had died before day 3 were excluded. The clinically important difference was defined as an absolute reduction in mortality of 20 percentage points in the convalescent-plasma group as compared with the control group.
RESULTS
A total of 84 patients who were treated with plasma were included in the primary analysis. At baseline, the convalescent-plasma group had slightly higher cycle-threshold values and a shorter duration of symptoms than did the control group, along with a higher frequency of eye redness and difficulty in swallowing. From day 3 to day 16 after diagnosis, the risk of death was 31% in the convalescent-plasma group and 38% in the control group (risk difference, -7 percentage points; 95% confidence interval [CI], -18 to 4). The difference was reduced after adjustment for age and cycle-threshold value (adjusted risk difference, -3 percentage points; 95% CI, -13 to 8). No serious adverse reactions associated with the use of convalescent plasma were observed.
CONCLUSIONS
The transfusion of up to 500 ml of convalescent plasma with unknown levels of neutralizing antibodies in 84 patients with confirmed EVD was not associated with a significant improvement in survival. (Funded by the European Union's Horizon 2020 Research and Innovation Program and others; ClinicalTrials.gov number, NCT02342171.).
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
Vaccines. 2024 July 26; Volume 12 (Issue 8); 828.; DOI:10.3390/vaccines12080828
Choi EM, Kasonia K, Kavunga-Membo H, Mukadi-Bamuleka D, Soumah A, et al.
Vaccines. 2024 July 26; Volume 12 (Issue 8); 828.; DOI:10.3390/vaccines12080828
During the 2018–2020 Ebola virus disease outbreak in Democratic Republic of the Congo, a phase 3 trial of the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine (DRC-EB-001) commenced in Goma, with participants being offered the two-dose regimen given 56 days apart. Suspension of trial activities in 2020 due to the COVID-19 pandemic led to some participants receiving a late dose 2 outside the planned interval. Blood samples were collected from adults, adolescents, and children prior to their delayed dose 2 vaccination and 21 days after, and tested for IgG binding antibodies against Ebola virus glycoprotein using the Filovirus Animal Nonclinical Group (FANG) ELISA. Results from 133 participants showed a median two-dose interval of 9.3 months. The pre-dose 2 antibody geometric mean concentration (GMC) was 217 ELISA Units (EU)/mL (95% CI 157; 301) in adults, 378 EU/mL (281; 510) in adolescents, and 558 EU/mL (471; 661) in children. At 21 days post-dose 2, the GMC increased to 22,194 EU/mL (16,726; 29,449) in adults, 37,896 EU/mL (29,985; 47,893) in adolescents, and 34,652 EU/mL (27,906; 43,028) in children. Participants receiving a delayed dose 2 had a higher GMC at 21 days post-dose 2 than those who received a standard 56-day regimen in other African trials, but similar to those who received the regimen with an extended interval.
Conference Material > Abstract
Burza S, Mahajan R, Edwards T, Shandilya C, Pereira AL, et al.
MSF Scientific Days International 2021: Research. 2021 May 19
INTRODUCTION
Most interventions for community-based management of severe acute malnutrition (CM-SAM) worldwide utilise mid-upper arm circumference (MUAC) <115mm for eligibility and ≥125mm for discharge. However, this discharge criterion is based on very limited evidence, with no data from the Indian subcontinent. India, home to over one-third of malnourished children globally, provides facility-based care based on weight-for-height with no guidelines for CM-SAM. Previous observational data suggests relapse in children reaching ≥120mm is similar to that for ≥125mm, whilst duration of treatment required to achieve ≥125mm is nearly doubled, with higher default rates. This trial in the state of Jharkhand, India investigated whether discharge with MUAC ≥120mm is non-inferior to MUAC ≥125mm for risk of relapse to SAM or death.
METHODS
We conducted a multicentre randomized controlled noninferiority trial for SAM children aged between six and 59 months across 46 centres in Jharkhand, India. Over 12 months, children with MUAC<115mm and without oedema at admission were randomly allocated to be discharged either at MUAC ≥120 mm or MUAC ≥125mm. Endpoints were status at three months (primary) and six months (secondary) after reaching their allocated discharge MUAC. Non-inferiority was concluded if the upper bound (UB) of a one-sided 95% confidence interval was within a pre-defined 13% margin, based on pragmatic operational indicators.
ETHICS
This study was approved by the MSF Ethics Review Board and by the Ethical Review Boards of the Rajendra Institute of Medical Sciences, Ranchi and Jawaharlal Nehru University, New Delhi, India, and London School of Hygiene & Tropical Medicine, UK. Clinical Trials Registry – India number, CTRI/2017/12/010743.
RESULTS
Of 633 children enrolled, 316 were allocated to the standard of care arm (discharge at ≥125mm) and 317 to the ≥120mm arm. No significant clinical-epidemiological differences were detected between cohorts not reaching their allocated discharge MUAC, however there was a higher proportion of treatment non-response (17.5% vs 9%) in the 125mm arm. Of 194 and 236 children reaching discharge criteria in each arm respectively, 176 and 216 were eligible for intention-to-treat analysis. For the standard of care arm, 42% of children were male, with a mean age of 12.6 months (standard deviation, SD; 7.9); for the ≥120mm arm, 41% were male, with a mean age of 12.1 months (SD; 7.1). Overall, non-inferiority was observed within three months; unadjusted risk difference (RD) 6.4%, 95% UB=11.6%, ≥125mm: n=14 (8.0%; 14 relapse, 0 death), ≥120mm: n=31 (14.4%; 30 relapse, 1 death). In pre-specified stratified analyses, non-inferiority was observed in children with MUAC 110-114mm at enrolment (N=285, RD 2.0%, 95% UB 7.5%); however, inferiority was observed with MUAC<110mm (N=107, RD 17.5%, 95% UB 29.0%). In stratified secondary outcome analyses at six months, conclusions were similar.
CONCLUSION
Using a non-inferiority margin of 13%, results support ≥120mm as a discharge criterion in children admitted with MUAC 110-114mm, but not in those with MUAC<110mm. This margin in children discharged earlier needs to be balanced against greater capacity for programmatic coverage. Considering over two thirds of children are admitted with MUAC 110-114mm, defining discharge criteria by admission MUAC may have important implications on increasing capacity and cost-effectiveness of CM-SAM programming in India.
Most interventions for community-based management of severe acute malnutrition (CM-SAM) worldwide utilise mid-upper arm circumference (MUAC) <115mm for eligibility and ≥125mm for discharge. However, this discharge criterion is based on very limited evidence, with no data from the Indian subcontinent. India, home to over one-third of malnourished children globally, provides facility-based care based on weight-for-height with no guidelines for CM-SAM. Previous observational data suggests relapse in children reaching ≥120mm is similar to that for ≥125mm, whilst duration of treatment required to achieve ≥125mm is nearly doubled, with higher default rates. This trial in the state of Jharkhand, India investigated whether discharge with MUAC ≥120mm is non-inferior to MUAC ≥125mm for risk of relapse to SAM or death.
METHODS
We conducted a multicentre randomized controlled noninferiority trial for SAM children aged between six and 59 months across 46 centres in Jharkhand, India. Over 12 months, children with MUAC<115mm and without oedema at admission were randomly allocated to be discharged either at MUAC ≥120 mm or MUAC ≥125mm. Endpoints were status at three months (primary) and six months (secondary) after reaching their allocated discharge MUAC. Non-inferiority was concluded if the upper bound (UB) of a one-sided 95% confidence interval was within a pre-defined 13% margin, based on pragmatic operational indicators.
ETHICS
This study was approved by the MSF Ethics Review Board and by the Ethical Review Boards of the Rajendra Institute of Medical Sciences, Ranchi and Jawaharlal Nehru University, New Delhi, India, and London School of Hygiene & Tropical Medicine, UK. Clinical Trials Registry – India number, CTRI/2017/12/010743.
RESULTS
Of 633 children enrolled, 316 were allocated to the standard of care arm (discharge at ≥125mm) and 317 to the ≥120mm arm. No significant clinical-epidemiological differences were detected between cohorts not reaching their allocated discharge MUAC, however there was a higher proportion of treatment non-response (17.5% vs 9%) in the 125mm arm. Of 194 and 236 children reaching discharge criteria in each arm respectively, 176 and 216 were eligible for intention-to-treat analysis. For the standard of care arm, 42% of children were male, with a mean age of 12.6 months (standard deviation, SD; 7.9); for the ≥120mm arm, 41% were male, with a mean age of 12.1 months (SD; 7.1). Overall, non-inferiority was observed within three months; unadjusted risk difference (RD) 6.4%, 95% UB=11.6%, ≥125mm: n=14 (8.0%; 14 relapse, 0 death), ≥120mm: n=31 (14.4%; 30 relapse, 1 death). In pre-specified stratified analyses, non-inferiority was observed in children with MUAC 110-114mm at enrolment (N=285, RD 2.0%, 95% UB 7.5%); however, inferiority was observed with MUAC<110mm (N=107, RD 17.5%, 95% UB 29.0%). In stratified secondary outcome analyses at six months, conclusions were similar.
CONCLUSION
Using a non-inferiority margin of 13%, results support ≥120mm as a discharge criterion in children admitted with MUAC 110-114mm, but not in those with MUAC<110mm. This margin in children discharged earlier needs to be balanced against greater capacity for programmatic coverage. Considering over two thirds of children are admitted with MUAC 110-114mm, defining discharge criteria by admission MUAC may have important implications on increasing capacity and cost-effectiveness of CM-SAM programming in India.
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
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.
Journal Article > ResearchFull Text
Vaccines. 2024 July 23; Volume 12 (Issue 8); 825.; DOI:10.3390/vaccines12080825
Kavunga-Membo H, Watson-Jones D, Kasonia K, Edwards T, Camacho A, et al.
Vaccines. 2024 July 23; Volume 12 (Issue 8); 825.; DOI:10.3390/vaccines12080825
During the 2018–2020 Ebola virus disease (EVD) outbreak, residents in Goma, Democratic Republic of the Congo, were offered a two-dose prophylactic EVD vaccine. This was the first study to evaluate the safety of this vaccine in pregnant women. Adults, including pregnant women, and children aged ≥1 year old were offered the Ad26.ZEBOV (day 0; dose 1), MVA-BN-Filo (day 56; dose 2) EVD vaccine through an open-label clinical trial. In total, 20,408 participants, including 6635 (32.5%) children, received dose 1. Fewer than 1% of non-pregnant participants experienced a serious adverse event (SAE) following dose 1; one SAE was possibly related to the Ad26.ZEBOV vaccine. Of the 1221 pregnant women, 371 (30.4%) experienced an SAE, with caesarean section being the most common event. No SAEs in pregnant women were considered related to vaccination. Of 1169 pregnancies with a known outcome, 55 (4.7%) ended in a miscarriage, and 30 (2.6%) in a stillbirth. Eleven (1.0%) live births ended in early neonatal death, and five (0.4%) had a congenital abnormality. Overall, 188/891 (21.1%) were preterm births and 79/1032 (7.6%) had low birth weight. The uptake of the two-dose regimen was high: 15,328/20,408 (75.1%). The vaccine regimen was well-tolerated among the study participants, including pregnant women, although further data, ideally from controlled trials, are needed in this crucial group.