Journal Article > LetterFull Text
Lancet Global Health. 2014 August 19; Volume 2 (Issue 8); DOI:10.1016/S2214-109X(14)70252-9
Dorlo TPC, Balasegaram M
Lancet Global Health. 2014 August 19; Volume 2 (Issue 8); DOI:10.1016/S2214-109X(14)70252-9
Journal Article > ResearchFull Text
Trans R Soc Trop Med Hyg. 2008 October 21; Volume 103 (Issue 3); DOI:10.1016/j.trstmh.2008.09.005
Balasegaram M, Young H, Chappuis F, Priotto G, Raguenaud ME, et al.
Trans R Soc Trop Med Hyg. 2008 October 21; Volume 103 (Issue 3); DOI:10.1016/j.trstmh.2008.09.005
This paper describes the effectiveness of first-line regimens for stage 2 human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense infection in nine Médecins Sans Frontières HAT treatment programmes in Angola, Republic of Congo, Sudan and Uganda. Regimens included eflornithine and standard- and short-course melarsoprol. Outcomes for 10461 naïve stage 2 patients fitting a standardised case definition and allocated to one of the above regimens were analysed by intention-to-treat analysis. Effectiveness was quantified by the case fatality rate (CFR) during treatment, the proportion probably and definitely cured and the Kaplan-Meier probability of relapse-free survival at 12 months and 24 months post admission. The CFR was similar for the standard- and short-course melarsoprol regimens (4.9% and 4.2%, respectively). The CFR for eflornithine was 1.2%. Kaplan-Meier survival probabilities varied from 71.4-91.8% at 1 year and 56.5-87.9% at 2 years for standard-course melarsoprol, to 73.0-91.1% at 1 year for short-course melarsoprol, and 79.9-97.4% at 1 year and 68.6-93.7% at 2 years for eflornithine. With the exception of one programme, survival at 12 months was >90% for eflornithine, whilst for melarsoprol it was <90% except in two sites. Eflornithine is recommended where feasible, especially in areas with low melarsoprol effectiveness.
Journal Article > ResearchFull Text
Trans R Soc Trop Med Hyg. 2007 January 1; Volume 101 (Issue 1); DOI:10.1016/j.trstmh.2006.02.005
Mueller M, Ritmeijer KKD, Balasegaram M, Koummuki Y, Santana MR, et al.
Trans R Soc Trop Med Hyg. 2007 January 1; Volume 101 (Issue 1); DOI:10.1016/j.trstmh.2006.02.005
In Sudan, two treatments are currently registered for visceral leishmaniasis: sodium stibogluconate (SSG) as first line and liposomal amphotericin B (AmBisome) as second line. We present 64 patients (52 relapse cases to SSG, 12 new but complicated cases) treated with AmBisome in eastern Sudan. AmBisome was administered at 2.5-8.2mg/kg (15-49mg/kg in total) per dose six times (days 1, 2, 3, 5, 10, 15) as an intravenous infusion. We measured outcome according to clinical response and parasitological clearance (lymph node aspiration). Patient outcomes fell into three groups: group 1, clinical responders (cured) with a negative test of cure (n=35); group 2, clinical responders with a positive test of cure (n=19); group 3, clinical non-responders (failures) with a positive test of cure (n=10). Of the 10 failures, six were already relapse cases. All of group 3, and 15 from group 2, were also treated with additional SSG (20mg/kg intramuscularly daily for 30-50 d) with resulting clinical and parasitological improvement. Parasite persistence and clinical failure were associated with a higher parasite density on admission (P<0.002) and underlying immunosuppressive disease: tuberculosis (three cases) or HIV (two cases). Because AmBisome monotherapy may fail in Sudan, a combination of AmBisome and SSG is recommended for relapse cases.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2014 January 2; Volume 8 (Issue 1); e2603.; DOI:10.1371/journal.pntd.0002603
Burza S, Sinha PK, Mahajan R, Lima MA, Mitra G, et al.
PLoS Negl Trop Dis. 2014 January 2; Volume 8 (Issue 1); e2603.; DOI:10.1371/journal.pntd.0002603
Visceral Leishmaniasis (VL; also known as Kala-azar) is an ultimately fatal disease endemic in Bihar. A 2007 observational cohort study in Bihar of 251 patients with VL treated with 20 mg/Kg intravenous liposomal amphotericin B (Ambisome) demonstrated a 98% cure rate at 6-months. Between July 2007 and August 2012, Médecins Sans Frontières (MSF) and the Rajendra Memorial Research Institute (RMRI) implemented a VL treatment project in Bihar, India-an area highly endemic for Leishmania donovani-using this regimen as first-line treatment.
Protocol > Research Study
Diro EGJ, Griensven JV, Woldegebreal T, Belew Z, Taye M, et al.
2018 July 1
2.1 OBJECTIVES
2.1.1 General objective:
To document the effectiveness, safety and feasibility of monthly PM secondary prophylaxis (PSP) in VL/HIV co-infected patients that have documented parasite clearance after VL treatment when used for prevention of VL relapse.
2.1.2 Specific objectives of the primary study period
2.1.2.1 Primary objectives
In VL/HIV co-infected patients that have documented parasite clearance after VL treatment:
- to assess the effectiveness of PSP in terms of preventing relapse and death;
- to assess the safety of PSP in terms of drug-related serious adverse events or permanent drug discontinuations due to adverse events;
- to assess the feasibility of PSP in terms of number of patients compliant to therapy
during the first year of monthly PM secondary prophylaxis.
2.1.2.2 Secondary objectives;
In VL/HIV co-infected patients that have documented parasite clearance after VL treatment:
- to assess the safety of PSP in terms of:
- drug-related non-serious adverse events
- serious adverse events (drug-related or not)
- to assess the feasibility of PSP in terms of:
- number of treatment interruptions/discontinuations,
- number of therapeutic interventions needed to treat adverse drug reactions
2.1.1 General objective:
To document the effectiveness, safety and feasibility of monthly PM secondary prophylaxis (PSP) in VL/HIV co-infected patients that have documented parasite clearance after VL treatment when used for prevention of VL relapse.
2.1.2 Specific objectives of the primary study period
2.1.2.1 Primary objectives
In VL/HIV co-infected patients that have documented parasite clearance after VL treatment:
- to assess the effectiveness of PSP in terms of preventing relapse and death;
- to assess the safety of PSP in terms of drug-related serious adverse events or permanent drug discontinuations due to adverse events;
- to assess the feasibility of PSP in terms of number of patients compliant to therapy
during the first year of monthly PM secondary prophylaxis.
2.1.2.2 Secondary objectives;
In VL/HIV co-infected patients that have documented parasite clearance after VL treatment:
- to assess the safety of PSP in terms of:
- drug-related non-serious adverse events
- serious adverse events (drug-related or not)
- to assess the feasibility of PSP in terms of:
- number of treatment interruptions/discontinuations,
- number of therapeutic interventions needed to treat adverse drug reactions
Journal Article > CommentaryFull Text
Clin Microbiol Infect. 2016 June 29; Volume 22 (Issue 8); DOI:10.1016/j.cmi.2016.06.012
Reid J, Balasegaram M
Clin Microbiol Infect. 2016 June 29; Volume 22 (Issue 8); DOI:10.1016/j.cmi.2016.06.012
Earlier this year a series of advertisements appeared in London's Westminster tube stations asking viewers to consider a seemingly simple question, 'what does it take to make one medicine?' But as it turns out, this question is not so simple to answer. In this commentary we highlight some key considerations and questions on what it takes to make one medicine, and what it could take to develop medicines that meet people's health needs and are accessible and affordable for all who need them.
Journal Article > Short ReportFull Text
PLOS Med. 2017 April 18; Volume 14 (Issue 4); e1002276.; DOI:10.1371/journal.pmed.1002276
Balasegaram M, Kolb P, McKew J, Menon J, Olliaro PL, et al.
PLOS Med. 2017 April 18; Volume 14 (Issue 4); e1002276.; DOI:10.1371/journal.pmed.1002276
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2018 October 22; Volume 12 (Issue 10); e0006830.; DOI:10.1371/journal.pntd.0006830
Goyal V, Mahajan R, Pandey K, Singh SN, Singh RS, et al.
PLoS Negl Trop Dis. 2018 October 22; Volume 12 (Issue 10); e0006830.; DOI:10.1371/journal.pntd.0006830
BACKGROUND
In 2010, WHO recommended the use of new short-course treatment regimens in kala-azar elimination efforts for the Indian subcontinent. Although phase 3 studies have shown excellent results, there remains a lack of evidence on a wider treatment population and the safety and effectiveness of these regimens under field conditions.
METHODS
This was an open label, prospective, non-randomized, non-comparative, multi-centric trial conducted within public health facilities in two highly endemic districts and a specialist referral centre in Bihar, India. Three treatment regimens were tested: single dose AmBisome (SDA), concomitant miltefosine and paromomycin (Milt+PM), and concomitant AmBisome and miltefosine (AmB+Milt). Patients with complicated disease or significant co-morbidities were treated in the SDA arm. Sample sizes were set at a minimum of 300 per arm, taking into account inter-site variation and an estimated failure risk of 5% with 5% precision. Outcomes of drug effectiveness and safety were measured at 6 months. The trial was prospectively registered with the Clinical Trials Registry India: CTRI/2012/08/002891.
RESULTS
Out of 1,761 patients recruited, 50.6% (n = 891) received SDA, 20.3% (n = 358) AmB+Milt and 29.1% (n = 512) Milt+PM. In the ITT analysis, the final cure rates were SDA 91.4% (95% CI 89.3-93.1), AmB+Milt 88.8% (95% CI 85.1-91.9) and Milt+PM 96.9% (95% CI 95.0-98.2). In the complete case analysis, cure rates were SDA 95.5% (95% CI 93.9-96.8), AmB+Milt 95.5% (95% CI 92.7-97.5) and Milt+PM 99.6% (95% CI 98.6-99.9). All three regimens were safe, with 5 severe adverse events in the SDA arm, two of which were considered to be drug related.
CONCLUSION
All regimens showed acceptable outcomes and safety profiles in a range of patients under field conditions. Phase IV field-based studies, although extremely rare for neglected tropical diseases, are good practice and an important step in validating the results of more restrictive hospital-based studies before widespread implementation, and in this case contributed to national level policy change in India.
In 2010, WHO recommended the use of new short-course treatment regimens in kala-azar elimination efforts for the Indian subcontinent. Although phase 3 studies have shown excellent results, there remains a lack of evidence on a wider treatment population and the safety and effectiveness of these regimens under field conditions.
METHODS
This was an open label, prospective, non-randomized, non-comparative, multi-centric trial conducted within public health facilities in two highly endemic districts and a specialist referral centre in Bihar, India. Three treatment regimens were tested: single dose AmBisome (SDA), concomitant miltefosine and paromomycin (Milt+PM), and concomitant AmBisome and miltefosine (AmB+Milt). Patients with complicated disease or significant co-morbidities were treated in the SDA arm. Sample sizes were set at a minimum of 300 per arm, taking into account inter-site variation and an estimated failure risk of 5% with 5% precision. Outcomes of drug effectiveness and safety were measured at 6 months. The trial was prospectively registered with the Clinical Trials Registry India: CTRI/2012/08/002891.
RESULTS
Out of 1,761 patients recruited, 50.6% (n = 891) received SDA, 20.3% (n = 358) AmB+Milt and 29.1% (n = 512) Milt+PM. In the ITT analysis, the final cure rates were SDA 91.4% (95% CI 89.3-93.1), AmB+Milt 88.8% (95% CI 85.1-91.9) and Milt+PM 96.9% (95% CI 95.0-98.2). In the complete case analysis, cure rates were SDA 95.5% (95% CI 93.9-96.8), AmB+Milt 95.5% (95% CI 92.7-97.5) and Milt+PM 99.6% (95% CI 98.6-99.9). All three regimens were safe, with 5 severe adverse events in the SDA arm, two of which were considered to be drug related.
CONCLUSION
All regimens showed acceptable outcomes and safety profiles in a range of patients under field conditions. Phase IV field-based studies, although extremely rare for neglected tropical diseases, are good practice and an important step in validating the results of more restrictive hospital-based studies before widespread implementation, and in this case contributed to national level policy change in India.
Journal Article > CommentaryFull Text
Lancet. 2015 November 18; Volume 387 (Issue 10014); DOI:10.1016/S0140-6736(15)00547-4
Mendelson M, Rottingen JA, Gopinathan U, Hamer DH, Wertheim H, et al.
Lancet. 2015 November 18; Volume 387 (Issue 10014); DOI:10.1016/S0140-6736(15)00547-4
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.