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).
Conference Material > Abstract
Sterk E, Schramm B, Riccio E, Gabut M, Fontana L, et al.
MSF Scientific Day International 2024. 2024 May 16; DOI:10.57740/Dz2BnS7
INTRODUCTION
The 2014 West Africa Ebola outbreak underlined inadequacies of current personal protective equipment (PPE), such as being uncomfortable and hot, causing excessive sweating and rapid exhaustion, and limiting interactions between health workers and patients. The smartPPE development project responded to the urgent need for a more comfortable, simpler, and sustainable PPE solution for filovirus-outbreak front-line workers. A one- piece, reusable smartPPE with ventilation system was developed to address these challenges. We assessed ease-of-use, comfort, functionality, and perceived doffing-safety of the smartPPE prototype compared with currently used PPE (current-PPE) under simulated field conditions.
METHODS
In June 2023, we conducted a mixed-methods crossover usability study in a controlled high-heat/high-humidity indoor site in Brindisi, Italy. Ten test users (three female, seven with filovirus-front-line experience) assessed smartPPE and current- PPE in four guided sessions covering donning, (emergency) doffing, clinical tasks, and heavy physical WATSAN activities. User feedback was collected through structured questionnaires. Temperature, humidity, session duration, and vital signs were measured, and perceived exertion was assessed using Borg- scores (scale 6–20).
RESULTS
Median temperature and humidity were higher inside current- PPE than inside smartPPE (difference: 2.3°C [IQR 1.8–3.0] and 12.6 percentage points [8.8–19.6], respectively). Users endured heavy work sessions for significantly longer in smartPPE than in current-PPE (80.0 min [IQR 75–84] vs 49.5 min [45–56]). Median increases in body temperature (1.1°C [IQR 0.7–1.6] vs 0.7°C [0.3–0.9]; p<0.001) and respiratory rate (3.5 rpm [1–5] vs 1.5 rpm [0–3]; p=0.034), and reductions in O2 saturation (–2% [–5 to –1] vs –1.5% [–3 to 0]; p=0.027) were higher with current-PPE than with smartPPE. Peripheral vision was similarly rated, but hearing was compromised with smartPPE at ≥5 m. Median exertion- scores were lower for smartPPE (clinical tasks 8.5 [IQR 7–11] vs 15.5 [14–16] p<0.01; heavy physical activities 14 [13–17] vs 18 [17–20] p=0.035). All users preferred smartPPE for overall and thermal comfort, breathing, and doffing-safety; nine (90%) favoured it for non-verbal communication, eight (80%) for vision or longer-interval heavy WATSAN activities, six (60%) for longer- interval patient care, six (60%) for short-term clinical activities, and six (60%) for emergency doffing. Reported concerns were airflow obstruction while bending, hearing difficulties attributed to ventilation noise, and adjustments for headgear, ventilation, and suit fitting.
CONCLUSION
Test users confirmed the usability of smartPPE and favoured it, especially for doffing-safety, longer-interval clinical or physical work, and improved non-verbal interactions, whereas hearing was challenged by the ventilation. Adjustments are currently underway before design freeze. Stakeholder commitment will be crucial to ensure production at scale.
The 2014 West Africa Ebola outbreak underlined inadequacies of current personal protective equipment (PPE), such as being uncomfortable and hot, causing excessive sweating and rapid exhaustion, and limiting interactions between health workers and patients. The smartPPE development project responded to the urgent need for a more comfortable, simpler, and sustainable PPE solution for filovirus-outbreak front-line workers. A one- piece, reusable smartPPE with ventilation system was developed to address these challenges. We assessed ease-of-use, comfort, functionality, and perceived doffing-safety of the smartPPE prototype compared with currently used PPE (current-PPE) under simulated field conditions.
METHODS
In June 2023, we conducted a mixed-methods crossover usability study in a controlled high-heat/high-humidity indoor site in Brindisi, Italy. Ten test users (three female, seven with filovirus-front-line experience) assessed smartPPE and current- PPE in four guided sessions covering donning, (emergency) doffing, clinical tasks, and heavy physical WATSAN activities. User feedback was collected through structured questionnaires. Temperature, humidity, session duration, and vital signs were measured, and perceived exertion was assessed using Borg- scores (scale 6–20).
RESULTS
Median temperature and humidity were higher inside current- PPE than inside smartPPE (difference: 2.3°C [IQR 1.8–3.0] and 12.6 percentage points [8.8–19.6], respectively). Users endured heavy work sessions for significantly longer in smartPPE than in current-PPE (80.0 min [IQR 75–84] vs 49.5 min [45–56]). Median increases in body temperature (1.1°C [IQR 0.7–1.6] vs 0.7°C [0.3–0.9]; p<0.001) and respiratory rate (3.5 rpm [1–5] vs 1.5 rpm [0–3]; p=0.034), and reductions in O2 saturation (–2% [–5 to –1] vs –1.5% [–3 to 0]; p=0.027) were higher with current-PPE than with smartPPE. Peripheral vision was similarly rated, but hearing was compromised with smartPPE at ≥5 m. Median exertion- scores were lower for smartPPE (clinical tasks 8.5 [IQR 7–11] vs 15.5 [14–16] p<0.01; heavy physical activities 14 [13–17] vs 18 [17–20] p=0.035). All users preferred smartPPE for overall and thermal comfort, breathing, and doffing-safety; nine (90%) favoured it for non-verbal communication, eight (80%) for vision or longer-interval heavy WATSAN activities, six (60%) for longer- interval patient care, six (60%) for short-term clinical activities, and six (60%) for emergency doffing. Reported concerns were airflow obstruction while bending, hearing difficulties attributed to ventilation noise, and adjustments for headgear, ventilation, and suit fitting.
CONCLUSION
Test users confirmed the usability of smartPPE and favoured it, especially for doffing-safety, longer-interval clinical or physical work, and improved non-verbal interactions, whereas hearing was challenged by the ventilation. Adjustments are currently underway before design freeze. Stakeholder commitment will be crucial to ensure production at scale.
Conference Material > Poster
Ashakin KA, Hadiuzzaman M, Firuz W, Rahman A, Ben-Farhat J, et al.
Epicentre Scientific Day 2024. 2024 May 23
Journal Article > ResearchFull Text
Genome Med. 2020 November 25; Volume 12; DOI:10.1186/s13073-020-00793-8
Beckert P, Sanchez-Padilla E, Merker M, Dreyer V, Kohl TA, et al.
Genome Med. 2020 November 25; Volume 12; DOI:10.1186/s13073-020-00793-8
Background
Multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains not detected by commercial molecular drug susceptibility testing (mDST) assays due to the RpoB I491F resistance mutation are threatening the control of MDR tuberculosis (MDR-TB) in Eswatini.
Methods
We investigate the evolution and spread of MDR strains in Eswatini with a focus on bedaquiline (BDQ) and clofazimine (CFZ) resistance using whole-genome sequencing in two collections ((1) national drug resistance survey, 2009–2010; (2) MDR strains from the Nhlangano region, 2014–2017).
Results
MDR strains in collection 1 had a high cluster rate (95%, 117/123 MDR strains) with 55% grouped into the two largest clusters (gCL3, n = 28; gCL10, n = 40). All gCL10 isolates, which likely emerged around 1993 (95% highest posterior density 1987–1998), carried the mutation RpoB I491F that is missed by commercial mDST assays. In addition, 21 (53%) gCL10 isolates shared a Rv0678 M146T mutation that correlated with elevated minimum inhibitory concentrations (MICs) to BDQ and CFZ compared to wild type isolates. gCL10 isolates with the Rv0678 M146T mutation were also detected in collection 2.
Conclusion
The high clustering rate suggests that transmission has been driving the MDR-TB epidemic in Eswatini for three decades. The presence of MDR strains in Eswatini that are not detected by commercial mDST assays and have elevated MICs to BDQ and CFZ potentially jeopardizes the successful implementation of new MDR-TB treatment guidelines. Measures to limit the spread of these outbreak isolates need to be implemented urgently.
Multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains not detected by commercial molecular drug susceptibility testing (mDST) assays due to the RpoB I491F resistance mutation are threatening the control of MDR tuberculosis (MDR-TB) in Eswatini.
Methods
We investigate the evolution and spread of MDR strains in Eswatini with a focus on bedaquiline (BDQ) and clofazimine (CFZ) resistance using whole-genome sequencing in two collections ((1) national drug resistance survey, 2009–2010; (2) MDR strains from the Nhlangano region, 2014–2017).
Results
MDR strains in collection 1 had a high cluster rate (95%, 117/123 MDR strains) with 55% grouped into the two largest clusters (gCL3, n = 28; gCL10, n = 40). All gCL10 isolates, which likely emerged around 1993 (95% highest posterior density 1987–1998), carried the mutation RpoB I491F that is missed by commercial mDST assays. In addition, 21 (53%) gCL10 isolates shared a Rv0678 M146T mutation that correlated with elevated minimum inhibitory concentrations (MICs) to BDQ and CFZ compared to wild type isolates. gCL10 isolates with the Rv0678 M146T mutation were also detected in collection 2.
Conclusion
The high clustering rate suggests that transmission has been driving the MDR-TB epidemic in Eswatini for three decades. The presence of MDR strains in Eswatini that are not detected by commercial mDST assays and have elevated MICs to BDQ and CFZ potentially jeopardizes the successful implementation of new MDR-TB treatment guidelines. Measures to limit the spread of these outbreak isolates need to be implemented urgently.
Journal Article > Meta-AnalysisFull Text
Am J Trop Med Hyg. 2014 July 21; Volume 91 (Issue 4); 833-43.; DOI:10.4269/ajtmh.14-0031
Venkatesan M, Gadalla NB, Stepniewska K, Dahal P, Nsanzabana C, et al.
Am J Trop Med Hyg. 2014 July 21; Volume 91 (Issue 4); 833-43.; DOI:10.4269/ajtmh.14-0031
Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001: were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.
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 > Short ReportFull Text
J Acquir Immune Defic Syndr. 2021 April 1; Volume Publish Ahead of Print; DOI:10.1097/QAI.0000000000002689
Bossard C, Schramm B, Wanjala S, Jain L, Mucinya G, et al.
J Acquir Immune Defic Syndr. 2021 April 1; Volume Publish Ahead of Print; DOI:10.1097/QAI.0000000000002689
Journal Article > ResearchFull Text
J Clin Microbiol. 2012 May 30; Volume 50 (Issue 8); DOI:10.1128/JCM.01232-12
Schramm B, Hewison CCH, Bonte L, Jones W, Camelique O, et al.
J Clin Microbiol. 2012 May 30; Volume 50 (Issue 8); DOI:10.1128/JCM.01232-12
Simple tuberculosis (TB) treatment monitoring tools are needed. We assessed the performance of fluorescein-diacetate (FDA) smear microscopy for detection of viable Mycobacterium tuberculosis in sputum specimens (n = 288) of TB cases under treatment compared to culture (17.4% culture positivity). FDA sensitivity was moderate (83.7% [95% confidence interval {CI}, 70.3 to 92.6]), and specificity was low (66.1% [59.5 to 72.2]). The good negative predictive value (94.8% [90.1 to 97.8]) and negative likelihood ratio (0.2) suggest using this method to rule out treatment failure in settings without access to culture.
Conference Material > Poster
Akem TE, Schramm B, Akeen WW, Singh SN, Adimw M, et al.
Epicentre Scientific Day 2024. 2024 May 23
Journal Article > ResearchFull Text
Malar J. 2011 May 18; Volume 10 (Issue 1); 132.; DOI:10.1186/1475-2875-10-132
De Beaudrap P, Nabasumba C, Grandesso F, Turyakira E, Schramm B, et al.
Malar J. 2011 May 18; Volume 10 (Issue 1); 132.; DOI:10.1186/1475-2875-10-132
BACKGROUND
Malaria is a major public health problem, especially for children. However, recent reports suggest a decline in the malaria burden. The aim of this study was to assess the change in the prevalence of malaria infection among children below five years of age between 2004 and 2010 in a mesoendemic area of Uganda and to analyse the risk factors of malaria infection.
METHODS
Two cross-sectional surveys were conducted in 2004 and in 2010 at the end of the rainy and dry seasons to measure the prevalence of P. falciparum infection among children less than five years of age. Rapid diagnostic tests and blood smears were used to diagnose malaria infection. In 2010, sampling was stratified by urban and rural areas. In each selected household, knowledge of malaria and bed nets, and bed net ownership and use, were assessed.
RESULTS
In 2004 and 2010, respectively, a total of 527 and 2,320 (999 in the urban area and 1,321 in rural areas) children less than five years old were enrolled. Prevalence of malaria infection declined from 43% (95% CI: 34-52) in 2004, to 23% (95% CI: 17-30) in rural areas in 2010 and 3% (95% CI: 2-5) in the urban area in 2010. From the rainy to dry season in 2010, prevalence decreased from 23% to 10% (95% CI: 6-14) in rural areas (P = 0.001) and remained stable from 3% to 4% (95% CI: 1-7) in the urban area (P = 0.9). The proportion of households reporting ownership and use of at least one bed net increased from 22.9% in 2004 to 64.7% in the urban area and 44.5% in rural areas in 2010 (P < 0.001). In 2010, the risk of malaria infection was consistently associated with child age and household wealth. In rural areas, malaria infection was also associated with geographic factors.
CONCLUSIONS
This study reports a significant drop in the prevalence of malaria infection among children below five years of age, paralleled by an uptake in bed-net use. However, prevalence remains unacceptably high in rural areas and is strongly associated with poverty.
Malaria is a major public health problem, especially for children. However, recent reports suggest a decline in the malaria burden. The aim of this study was to assess the change in the prevalence of malaria infection among children below five years of age between 2004 and 2010 in a mesoendemic area of Uganda and to analyse the risk factors of malaria infection.
METHODS
Two cross-sectional surveys were conducted in 2004 and in 2010 at the end of the rainy and dry seasons to measure the prevalence of P. falciparum infection among children less than five years of age. Rapid diagnostic tests and blood smears were used to diagnose malaria infection. In 2010, sampling was stratified by urban and rural areas. In each selected household, knowledge of malaria and bed nets, and bed net ownership and use, were assessed.
RESULTS
In 2004 and 2010, respectively, a total of 527 and 2,320 (999 in the urban area and 1,321 in rural areas) children less than five years old were enrolled. Prevalence of malaria infection declined from 43% (95% CI: 34-52) in 2004, to 23% (95% CI: 17-30) in rural areas in 2010 and 3% (95% CI: 2-5) in the urban area in 2010. From the rainy to dry season in 2010, prevalence decreased from 23% to 10% (95% CI: 6-14) in rural areas (P = 0.001) and remained stable from 3% to 4% (95% CI: 1-7) in the urban area (P = 0.9). The proportion of households reporting ownership and use of at least one bed net increased from 22.9% in 2004 to 64.7% in the urban area and 44.5% in rural areas in 2010 (P < 0.001). In 2010, the risk of malaria infection was consistently associated with child age and household wealth. In rural areas, malaria infection was also associated with geographic factors.
CONCLUSIONS
This study reports a significant drop in the prevalence of malaria infection among children below five years of age, paralleled by an uptake in bed-net use. However, prevalence remains unacceptably high in rural areas and is strongly associated with poverty.