Journal Article > CommentaryFull Text
PLoS Negl Trop Dis. 2015 November 12; Volume 9 (Issue 11); e0004075.; DOI:10.1371/journal.pntd.0004075
O'Brien DP, Ford NP, Vitoria M, Asiedu K, Calmy A, et al.
PLoS Negl Trop Dis. 2015 November 12; Volume 9 (Issue 11); e0004075.; DOI:10.1371/journal.pntd.0004075
Journal Article > ResearchFull Text
Malar J. 2013 July 17; Volume 12 (Issue 1); 250.; DOI:10.1186/1475-2875-12-250
Schramm B, Valeh P, Baudin E, Mazinda CS, Smith R, et al.
Malar J. 2013 July 17; Volume 12 (Issue 1); 250.; DOI:10.1186/1475-2875-12-250
BACKGROUND
Safety surveillance of widely used artemisinin-based combination therapy (ACT) is essential, but tolerability data in the over five years age group are largely anecdotal.
METHODS
Two open-label, randomized trials were conducted in Nimba County, Liberia: i) the main tolerability trial with 1,000 Plasmodium falciparum malaria patients aged over five years (Study-T), and, ii) an efficacy trial with a secondary objective of collecting tolerability data among 300 children age six to 59 months (Study-E). In both studies patients were randomized to fixed-dose artesunate-amodiaquine (ASAQ Winthrop®) or artemether-lumefantrine (AL, Coartem®), respectively. Clinical- and laboratory-adverse events (AEs) were recorded until day 28.
RESULTS
Study-T: most patients experienced at least one AE. Severe AEs were few, primarily asymptomatic blood system disorders or increased liver enzyme values. No treatment or study discontinuation occurred. Mild or moderate fatigue (39.8% vs 16.3%, p < 0.001), vomiting (7.1% vs 1.6%, p < 0.001), nausea (3.2% vs 1.0%, p = 0.01), and anaemia (14.9% vs 9.8%, p = 0.01) were more frequently recorded in the ASAQ versus AL arm. Study-E: mild or moderate AEs were common, including anaemia, fatigue, vomiting or diarrhoea. The few severe events were asymptomatic blood system disorders and four clinical events (pneumonia, malaria, vomiting and stomatitis).
CONCLUSION
Both ASAQ and AL were well tolerated in patients of all age groups. No unexpected AEs occurred. Certain mild or moderate AEs were more frequent in the ASAQ arm. Standardised safety surveillance should continue for all forms of ACT.
TRIAL REGISTRATION
The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN40020296, ISRCTN51688713, (http://www.controlled-trials.com).
Safety surveillance of widely used artemisinin-based combination therapy (ACT) is essential, but tolerability data in the over five years age group are largely anecdotal.
METHODS
Two open-label, randomized trials were conducted in Nimba County, Liberia: i) the main tolerability trial with 1,000 Plasmodium falciparum malaria patients aged over five years (Study-T), and, ii) an efficacy trial with a secondary objective of collecting tolerability data among 300 children age six to 59 months (Study-E). In both studies patients were randomized to fixed-dose artesunate-amodiaquine (ASAQ Winthrop®) or artemether-lumefantrine (AL, Coartem®), respectively. Clinical- and laboratory-adverse events (AEs) were recorded until day 28.
RESULTS
Study-T: most patients experienced at least one AE. Severe AEs were few, primarily asymptomatic blood system disorders or increased liver enzyme values. No treatment or study discontinuation occurred. Mild or moderate fatigue (39.8% vs 16.3%, p < 0.001), vomiting (7.1% vs 1.6%, p < 0.001), nausea (3.2% vs 1.0%, p = 0.01), and anaemia (14.9% vs 9.8%, p = 0.01) were more frequently recorded in the ASAQ versus AL arm. Study-E: mild or moderate AEs were common, including anaemia, fatigue, vomiting or diarrhoea. The few severe events were asymptomatic blood system disorders and four clinical events (pneumonia, malaria, vomiting and stomatitis).
CONCLUSION
Both ASAQ and AL were well tolerated in patients of all age groups. No unexpected AEs occurred. Certain mild or moderate AEs were more frequent in the ASAQ arm. Standardised safety surveillance should continue for all forms of ACT.
TRIAL REGISTRATION
The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN40020296, ISRCTN51688713, (http://www.controlled-trials.com).
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2021 February 12; Volume 15 (Issue 2); e0009023.; DOI:10.1371/journal.pntd.0009023
Alcoba G, Ochoa C, Martins SB, Ruiz de Castañeda R, Bolon I, et al.
PLoS Negl Trop Dis. 2021 February 12; Volume 15 (Issue 2); e0009023.; DOI:10.1371/journal.pntd.0009023
BACKGROUND
Worldwide, it is estimated that snakes bite 4.5-5.4 million people annually, 2.7 million of which are envenomed, and 81,000-138,000 die. The World Health Organization reported these estimates and recognized the scarcity of large-scale, community-based, epidemiological data. In this context, we developed the "Snake-Byte" project that aims at (i) quantifying and mapping the impact of snakebite on human and animal health, and on livelihoods, (ii) developing predictive models for medical, ecological and economic indicators, and (iii) analyzing geographic accessibility to healthcare. This paper exclusively describes the methodology we developed to collect large-scale primary data on snakebite in humans and animals in two hyper-endemic countries, Cameroon and Nepal.
METHODOLOGY/PRINCIPAL FINDINGS
We compared available methods on snakebite epidemiology and on multi-cluster survey development. Then, in line with those findings, we developed an original study methodology based on a multi-cluster random survey, enhanced by geospatial, One Health, and health economics components. Using a minimum hypothesized snakebite national incidence of 100/100,000/year and optimizing design effect, confidence level, and non-response margin, we calculated a sample of 61,000 people per country. This represented 11,700 households in Cameroon and 13,800 in Nepal. The random selection with probability proportional to size generated 250 clusters from all Cameroonian regions and all Nepalese Terai districts. Our household selection methodology combined spatial randomization and selection via high-resolution satellite images. After ethical approval in Switerland (CCER), Nepal (BPKIHS), and Cameroon (CNERSH), and informed written consent, our e-questionnaires included geolocated baseline demographic and socio-economic characteristics, snakebite clinical features and outcomes, healthcare expenditure, animal ownership, animal outcomes, snake identification, and service accessibility.
CONCLUSIONS/SIGNIFICANCE
This novel transdisciplinary survey methodology was subsequently used to collect countrywide snakebite envenoming data in Nepal and Cameroon. District-level incidence data should help health authorities to channel antivenom and healthcare allocation. This methodology, or parts thereof, could be easily adapted to other countries and to other Neglected Tropical Diseases.
Worldwide, it is estimated that snakes bite 4.5-5.4 million people annually, 2.7 million of which are envenomed, and 81,000-138,000 die. The World Health Organization reported these estimates and recognized the scarcity of large-scale, community-based, epidemiological data. In this context, we developed the "Snake-Byte" project that aims at (i) quantifying and mapping the impact of snakebite on human and animal health, and on livelihoods, (ii) developing predictive models for medical, ecological and economic indicators, and (iii) analyzing geographic accessibility to healthcare. This paper exclusively describes the methodology we developed to collect large-scale primary data on snakebite in humans and animals in two hyper-endemic countries, Cameroon and Nepal.
METHODOLOGY/PRINCIPAL FINDINGS
We compared available methods on snakebite epidemiology and on multi-cluster survey development. Then, in line with those findings, we developed an original study methodology based on a multi-cluster random survey, enhanced by geospatial, One Health, and health economics components. Using a minimum hypothesized snakebite national incidence of 100/100,000/year and optimizing design effect, confidence level, and non-response margin, we calculated a sample of 61,000 people per country. This represented 11,700 households in Cameroon and 13,800 in Nepal. The random selection with probability proportional to size generated 250 clusters from all Cameroonian regions and all Nepalese Terai districts. Our household selection methodology combined spatial randomization and selection via high-resolution satellite images. After ethical approval in Switerland (CCER), Nepal (BPKIHS), and Cameroon (CNERSH), and informed written consent, our e-questionnaires included geolocated baseline demographic and socio-economic characteristics, snakebite clinical features and outcomes, healthcare expenditure, animal ownership, animal outcomes, snake identification, and service accessibility.
CONCLUSIONS/SIGNIFICANCE
This novel transdisciplinary survey methodology was subsequently used to collect countrywide snakebite envenoming data in Nepal and Cameroon. District-level incidence data should help health authorities to channel antivenom and healthcare allocation. This methodology, or parts thereof, could be easily adapted to other countries and to other Neglected Tropical Diseases.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2020 June 25; Volume 14 (Issue 6); e0008334.; DOI:10.1371/journal.pntd.0008334
Alcoba G, Chabloz M, Eyong J, Wanda F, Ochoa C, et al.
PLoS Negl Trop Dis. 2020 June 25; Volume 14 (Issue 6); e0008334.; DOI:10.1371/journal.pntd.0008334
BACKGROUND
Snakebite envenoming causes 81,000-138,000 annual human deaths and pain, terror, or disability in 4.5-5.4 million victims. Accurate community-based epidemiological data is scarce. Our objective was to assess snakebite incidence, mortality, and health-seeking behavior, in an affected health district of Cameroon.
METHODS
We conducted a cross-sectional multicluster household survey in Akonolinga health district, Centre Region, Cameroon, from October to December 2016. Using probability-proportional-to-size, 20 villages were randomly selected, then, all inhabited households were systematically selected. Annual incidence and adjusted odds-ratio for predictors were estimated.
FINDINGS
Among the 9,924 participants, 66 suffered a snakebite during the past year: the resulting incidence is 665 (95%CI: 519-841) per 100,000 inhabitants per year. Victims were aged 5-75y (median: 34y), 53% were male and 57% farmer-cultivators. Two children died (case-fatality rate: 3%); 39 (59%) presented severity signs, including 2 (3%) neurotoxic syndromes, 20 (30%) systemic digestive syndromes, and 17 (26%) severe cytotoxic syndromes. Non-severe cases included 20 (30%) mild cytotoxic syndromes and 7 (11%) dry bites. Only two victims (3%) received antivenom. 59 (89%) used family traditional practices, 25 (38%) traditional healers, and 31 (47%) consulted health facilities. Median delays to these three care-options were 5, 45, and 60 minutes, respectively. Traditional treatments included incisions (n = 57; 86%), tourniquets (n = 51; 77%) and black-stones (n = 44; 67%). The two last procedures were also used in health facilities (n = 18). Consulting traditional healers was associated with severity (adjusted-OR: 19.6 (2.5-156), p = 0.005) and complications (aOR: 17.3, 2.4-123, p = 0.004). Long-term disabilities were subjective psychological trauma (n = 47; 71%), finger amputation (n = 1; 2%), ankylosis (n = 1; 2%) and chronic pain (n = 1; 2%).
CONCLUSIONS
We observed alarming levels of snakebite incidence, mortality, antivenom scarcity, and use of traditional medicine. It could represent several thousands of victims at national level. We suggested conducting a country-wide study, and improving antivenom supply, first-aid training, for traditional healers and health professionals.
Snakebite envenoming causes 81,000-138,000 annual human deaths and pain, terror, or disability in 4.5-5.4 million victims. Accurate community-based epidemiological data is scarce. Our objective was to assess snakebite incidence, mortality, and health-seeking behavior, in an affected health district of Cameroon.
METHODS
We conducted a cross-sectional multicluster household survey in Akonolinga health district, Centre Region, Cameroon, from October to December 2016. Using probability-proportional-to-size, 20 villages were randomly selected, then, all inhabited households were systematically selected. Annual incidence and adjusted odds-ratio for predictors were estimated.
FINDINGS
Among the 9,924 participants, 66 suffered a snakebite during the past year: the resulting incidence is 665 (95%CI: 519-841) per 100,000 inhabitants per year. Victims were aged 5-75y (median: 34y), 53% were male and 57% farmer-cultivators. Two children died (case-fatality rate: 3%); 39 (59%) presented severity signs, including 2 (3%) neurotoxic syndromes, 20 (30%) systemic digestive syndromes, and 17 (26%) severe cytotoxic syndromes. Non-severe cases included 20 (30%) mild cytotoxic syndromes and 7 (11%) dry bites. Only two victims (3%) received antivenom. 59 (89%) used family traditional practices, 25 (38%) traditional healers, and 31 (47%) consulted health facilities. Median delays to these three care-options were 5, 45, and 60 minutes, respectively. Traditional treatments included incisions (n = 57; 86%), tourniquets (n = 51; 77%) and black-stones (n = 44; 67%). The two last procedures were also used in health facilities (n = 18). Consulting traditional healers was associated with severity (adjusted-OR: 19.6 (2.5-156), p = 0.005) and complications (aOR: 17.3, 2.4-123, p = 0.004). Long-term disabilities were subjective psychological trauma (n = 47; 71%), finger amputation (n = 1; 2%), ankylosis (n = 1; 2%) and chronic pain (n = 1; 2%).
CONCLUSIONS
We observed alarming levels of snakebite incidence, mortality, antivenom scarcity, and use of traditional medicine. It could represent several thousands of victims at national level. We suggested conducting a country-wide study, and improving antivenom supply, first-aid training, for traditional healers and health professionals.
Journal Article > ResearchFull Text
Malar J. 2009 October 27; Volume 8; 241.; DOI:10.1186/1475-2875-8-241
Ashley EA, Touabi M, Ahrer M, Hutagalung R, Htun K, et al.
Malar J. 2009 October 27; Volume 8; 241.; DOI:10.1186/1475-2875-8-241
BACKGROUND: In areas where non-falciparum malaria is common rapid diagnostic tests (RDTs) capable of distinguishing malaria species reliably are needed. Such tests are often based on the detection of parasite lactate dehydrogenase (pLDH).
METHODS: In Dawei, southern Myanmar, three pLDH based RDTs (CareStart Malaria pLDH (Pan), CareStart Malaria pLDH (Pan, Pf) and OptiMAL-IT)were evaluated in patients presenting with clinically suspected malaria. Each RDT was read independently by two readers. A subset of patients with microscopically confirmed malaria had their RDTs repeated on days 2, 7 and then weekly until negative. At the end of the study, samples of study batches were sent for heat stability testing.
RESULTS: Between August and November 2007, 1004 patients aged between 1 and 93 years were enrolled in the study. Slide microscopy (the reference standard) diagnosed 213 Plasmodium vivax (Pv) monoinfections, 98 Plasmodium falciparum (Pf) mono-infections and no malaria in 650 cases. The sensitivities (sens) and specificities (spec), of the RDTs for the detection of malaria were- CareStart Malaria pLDH (Pan) test: sens 89.1% [CI95 84.2-92.6], spec 97.6% [CI95 96.5-98.4]. OptiMal-IT: Pf+/- other species detection: sens 95.2% [CI95 87.5-98.2], spec 94.7% [CI95 93.3-95.8]; non-Pf detection alone: sens 89.6% [CI95 83.6-93.6], spec 96.5% [CI95 94.8-97.7]. CareStart Malaria pLDH (Pan, Pf): Pf+/- other species: sens 93.5% [CI95 85.4-97.3], spec 97.4% [95.9-98.3]; non-Pf: sens 78.5% [CI95 71.1-84.4], spec 97.8% [CI95 96.3-98.7]. Inter-observer agreement was excellent for all tests (kappa > 0.9). The median time for the RDTs to become negative was two days for the CareStart Malaria tests and seven days for OptiMAL-IT. Tests were heat stable up to 90 days except for OptiMAL-IT (Pf specific pLDH stable to day 20 at 35 degrees C).
CONCLUSION: None of the pLDH-based RDTs evaluated was able to detect non-falciparum malaria with high sensitivity, particularly at low parasitaemias. OptiMAL-IT performed best overall and would perform best in an area of high malaria prevalence among screened fever cases. However, heat stability was unacceptable and the number of steps to perform this test is a significant drawback in the field. A reliable, heat-stable, highly sensitive RDT, capable of diagnosing all Plasmodium species has yet to be identified.
METHODS: In Dawei, southern Myanmar, three pLDH based RDTs (CareStart Malaria pLDH (Pan), CareStart Malaria pLDH (Pan, Pf) and OptiMAL-IT)were evaluated in patients presenting with clinically suspected malaria. Each RDT was read independently by two readers. A subset of patients with microscopically confirmed malaria had their RDTs repeated on days 2, 7 and then weekly until negative. At the end of the study, samples of study batches were sent for heat stability testing.
RESULTS: Between August and November 2007, 1004 patients aged between 1 and 93 years were enrolled in the study. Slide microscopy (the reference standard) diagnosed 213 Plasmodium vivax (Pv) monoinfections, 98 Plasmodium falciparum (Pf) mono-infections and no malaria in 650 cases. The sensitivities (sens) and specificities (spec), of the RDTs for the detection of malaria were- CareStart Malaria pLDH (Pan) test: sens 89.1% [CI95 84.2-92.6], spec 97.6% [CI95 96.5-98.4]. OptiMal-IT: Pf+/- other species detection: sens 95.2% [CI95 87.5-98.2], spec 94.7% [CI95 93.3-95.8]; non-Pf detection alone: sens 89.6% [CI95 83.6-93.6], spec 96.5% [CI95 94.8-97.7]. CareStart Malaria pLDH (Pan, Pf): Pf+/- other species: sens 93.5% [CI95 85.4-97.3], spec 97.4% [95.9-98.3]; non-Pf: sens 78.5% [CI95 71.1-84.4], spec 97.8% [CI95 96.3-98.7]. Inter-observer agreement was excellent for all tests (kappa > 0.9). The median time for the RDTs to become negative was two days for the CareStart Malaria tests and seven days for OptiMAL-IT. Tests were heat stable up to 90 days except for OptiMAL-IT (Pf specific pLDH stable to day 20 at 35 degrees C).
CONCLUSION: None of the pLDH-based RDTs evaluated was able to detect non-falciparum malaria with high sensitivity, particularly at low parasitaemias. OptiMAL-IT performed best overall and would perform best in an area of high malaria prevalence among screened fever cases. However, heat stability was unacceptable and the number of steps to perform this test is a significant drawback in the field. A reliable, heat-stable, highly sensitive RDT, capable of diagnosing all Plasmodium species has yet to be identified.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2009 June 23; Volume 3 (Issue 6); DOI:10.1371/journal.pntd.0000466
Porten K, Sailor K, Comte E, Njikap A, Sobry A, et al.
PLoS Negl Trop Dis. 2009 June 23; Volume 3 (Issue 6); DOI:10.1371/journal.pntd.0000466
BACKGROUND: Buruli ulcer (BU) is a chronic, indolent necrotizing disease of the skin and underlying tissues caused by Mycobacterium ulcerans, which may result in functional incapacity. In 2002, Médecins Sans Frontières (MSF) opened a BU programme in Akonolinga Hospital, Cameroon, offering antibiotic treatment, surgery and general medical care. Six hundred patients have been treated in the project to date. However, due to the nature of the disease and its stigmatization, determining the exact prevalence and burden of disease is difficult and current estimates may not reflect the magnitude of the problem. The objectives of this survey were to estimate the prevalence of BU in the health district of Akonolinga, describe the geographic extension of the highly endemic area within the health district, and determine the programme coverage and its geographical distribution. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional population survey using centric systematic area sampling (CSAS). A 15x15 km grid (quadrats of 225 km(2)) was overlaid on a map of Akonolinga district with its position chosen to maximize the area covered by the survey. Quadrats were selected if more than 50% of the quadrat was inside of the health district. The chiefdom located closest to the centre of each quadrat was selected and Buruli cases were identified using an active case finding strategy (the sensitivity of the strategy was estimated by capture-recapture). WHO-case definitions were used for nodules, plaque, ulcer, oedema and sequelae. Out of a total population of 103,000 inhabitants, 26,679 were surveyed within the twenty quadrats. Sensitivity of the case finding strategy was estimated to be 84% (95%CI 54-97%). The overall prevalence was 0.47% (n = 105) for all cases including sequelae and 0.25% (n = 56) for active stages of the disease. Five quadrats had a high prevalence of >0.6% to 0.9%, 5 a prevalence >0.3% to 0.6% and 10 quadrats <0.3%. The quadrats with the high prevalence were situated along the rivers Nyong and Mfoumou. Overall coverage of the project was 18% (12-27%) for all cases and 16% (9-18%) for active cases, but was limited to the quadrats neighbouring Akonolinga Hospital. CONCLUSIONS/SIGNIFICANCE: Prevalence was highest in the area neighbouring the Nyong River. Coverage was limited to the area close to the hospital and efforts have to be made to increase access to care in the high prevalence areas. Use of the CSAS method was particularly useful for project planning and to identify priority areas of intervention. An added benefit of the method is that the survey procedure incorporated an awareness campaign, providing information about the disease and treatment to the population.
Journal Article > ResearchFull Text
PLOS Med. 2008 August 5; Volume 5 (Issue 8); DOI:10.1371/journal.pmed.0050169
Guthmann JP, Checchi F, van den Broek IVF, Balkan S, Van Herp M, et al.
PLOS Med. 2008 August 5; Volume 5 (Issue 8); DOI:10.1371/journal.pmed.0050169
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2018 October 25; Volume 12 (Issue 10); DOI:10.1371/journal.pntd.0006716
Taieb F, Dub T, Madec Y, Tondeur L, Chippaux JP, et al.
PLoS Negl Trop Dis. 2018 October 25; Volume 12 (Issue 10); DOI:10.1371/journal.pntd.0006716
Snakebite has only recently been recognized as a neglected tropical disease by the WHO. Knowledge regarding snakebites and its care is poor both at the population level, and at the health care staff level. The goal of this study was to describe the level of knowledge and clinical practice regarding snakebite among health care staff from Cameroon.
Journal Article > ResearchFull Text
Malar J. 2013 July 17; Volume 12 (Issue 1); 251.; DOI:10.1186/1475-2875-12-251
Schramm B, Valeh P, Baudin E, Mazinda CS, Smith R, et al.
Malar J. 2013 July 17; Volume 12 (Issue 1); 251.; DOI:10.1186/1475-2875-12-251
BACKGROUND
Prospective efficacy monitoring of anti-malarial treatments is imperative for timely detection of resistance development. The in vivo efficacy of artesunate-amodiaquine (ASAQ) fixed-dose combination (FDC) was compared to that of artemether-lumefantrine (AL) among children aged six to 59 months in Nimba County, Liberia, where Plasmodium falciparum malaria is endemic and efficacy data are scarce.
METHODS
An open-label, randomized controlled non-inferiority trial compared the genotyping adjusted day 42 cure rates of ASAQ FDC (ASAQ Winthrop®) to AL (Coartem®) in 300 children aged six to 59 months with uncomplicated falciparum malaria. Inclusion was between December 2008 and May 2009. Randomization (1:1) was to a three-day observed oral regimen (ASAQ: once a day; AL: twice a day, given with fatty food). Day 7 desethylamodiaquine and lumefantrine blood-concentrations were also measured.
RESULTS
The day 42 genotyping-adjusted cure rate estimates were 97.3% [95% CI: 91.6-99.1] for ASAQ and 94.2% [88.1-97.2] for AL (Kaplan-Meier survival estimates). The difference in day 42 cure rates was -3.1% [upper limit 95% CI: 1.2%]. These results were confirmed by observed proportion of patients cured at day 42 on the per-protocol population. Parasite clearance was 100% (ASAQ) and 99.3% (AL) on day 3. The probability to remain free of re-infection was 0.55 [95% CI: 0.46-0.63] (ASAQ) and 0.66 [0.57-0.73] (AL) (p = 0.017).
CONCLUSIONS
Both ASAQ and AL were highly efficacious and ASAQ was non-inferior to AL. The proportion of patients with re-infection was high in both arms in this highly endemic setting. In 2010, ASAQ FDC was adopted as the first-line national treatment in Liberia. Continuous efficacy monitoring is recommended.
TRIAL REGISTRATION
The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN51688713, ISRCTN40020296.
Prospective efficacy monitoring of anti-malarial treatments is imperative for timely detection of resistance development. The in vivo efficacy of artesunate-amodiaquine (ASAQ) fixed-dose combination (FDC) was compared to that of artemether-lumefantrine (AL) among children aged six to 59 months in Nimba County, Liberia, where Plasmodium falciparum malaria is endemic and efficacy data are scarce.
METHODS
An open-label, randomized controlled non-inferiority trial compared the genotyping adjusted day 42 cure rates of ASAQ FDC (ASAQ Winthrop®) to AL (Coartem®) in 300 children aged six to 59 months with uncomplicated falciparum malaria. Inclusion was between December 2008 and May 2009. Randomization (1:1) was to a three-day observed oral regimen (ASAQ: once a day; AL: twice a day, given with fatty food). Day 7 desethylamodiaquine and lumefantrine blood-concentrations were also measured.
RESULTS
The day 42 genotyping-adjusted cure rate estimates were 97.3% [95% CI: 91.6-99.1] for ASAQ and 94.2% [88.1-97.2] for AL (Kaplan-Meier survival estimates). The difference in day 42 cure rates was -3.1% [upper limit 95% CI: 1.2%]. These results were confirmed by observed proportion of patients cured at day 42 on the per-protocol population. Parasite clearance was 100% (ASAQ) and 99.3% (AL) on day 3. The probability to remain free of re-infection was 0.55 [95% CI: 0.46-0.63] (ASAQ) and 0.66 [0.57-0.73] (AL) (p = 0.017).
CONCLUSIONS
Both ASAQ and AL were highly efficacious and ASAQ was non-inferior to AL. The proportion of patients with re-infection was high in both arms in this highly endemic setting. In 2010, ASAQ FDC was adopted as the first-line national treatment in Liberia. Continuous efficacy monitoring is recommended.
TRIAL REGISTRATION
The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN51688713, ISRCTN40020296.
Journal Article > ResearchFull Text
Open Forum Infect Dis. 2014 April 26; Volume 1 (Issue 1); DOI:10.1093/ofid/ofu021
Christinet V, Rossel L, Serafini M, Delhumeau C, Odermatt P, et al.
Open Forum Infect Dis. 2014 April 26; Volume 1 (Issue 1); DOI:10.1093/ofid/ofu021