Journal Article > ResearchFull Text
Malar J. 2021 September 9; Volume 20 (Issue 1); 366.; DOI:10.1186/s12936-021-03886-w
Taylor WRJ, Hoglund RM, Peerawaranun P, Nguyen TN, Hien TT, et al.
Malar J. 2021 September 9; Volume 20 (Issue 1); 366.; DOI:10.1186/s12936-021-03886-w
BACKGROUND
In many endemic areas, Plasmodium vivax malaria is predominantly a disease of young adults and children. International recommendations for radical cure recommend fixed target doses of 0.25 or 0.5 mg/kg/day of primaquine for 14 days in glucose-6-phosphate dehydrogenase normal patients of all ages. However, for many anti-malarial drugs, including primaquine, there is evidence that children have lower exposures than adults for the same weight-adjusted dose. The aim of the study was to develop 14-day weight-based and age-based primaquine regimens against high-frequency relapsing tropical P. vivax.
METHODS
The recommended adult target dose of 0.5 mg/kg/day (30 mg in a 60 kg patient) is highly efficacious against tropical P. vivax and was assumed to produce optimal drug exposure. Primaquine doses were calculated using allometric scaling to derive a weight-based primaquine regimen over a weight range from 5 to 100 kg. Growth curves were constructed from an anthropometric database of 53,467 individuals from the Greater Mekong Subregion (GMS) to define weight-for-age relationships. The median age associated with each weight was used to derive an age-based dosing regimen from the weight-based regimen.
RESULTS
The proposed weight-based regimen has 5 dosing bands: (i) 5-7 kg, 5 mg, resulting in 0.71-1.0 mg/kg/day; (ii) 8-16 kg, 7.5 mg, 0.47-0.94 mg/kg/day; (iii) 17-40 kg, 15 mg, 0.38-0.88 mg/kg/day; (iv) 41-80 kg, 30 mg, 0.37-0.73 mg/kg/day; and (v) 81-100 kg, 45 mg, 0.45-0.56 mg/kg/day. The corresponding age-based regimen had 4 dosing bands: 6-11 months, 5 mg, 0.43-1.0 mg/kg/day; (ii) 1-5 years, 7.5 mg, 0.35-1.25 mg/kg/day; (iii) 6-14 years, 15 mg, 0.30-1.36 mg/kg/day; and (iv) ≥ 15 years, 30 mg, 0.35-1.07 mg/kg/day.
CONCLUSION
The proposed weight-based regimen showed less variability around the primaquine dose within each dosing band compared to the age-based regimen and is preferred. Increased dose accuracy could be achieved by additional dosing bands for both regimens. The age-based regimen might not be applicable to regions outside the GMS, which must be based on local anthropometric data. Pharmacokinetic data in small children are needed urgently to inform the proposed regimens.
In many endemic areas, Plasmodium vivax malaria is predominantly a disease of young adults and children. International recommendations for radical cure recommend fixed target doses of 0.25 or 0.5 mg/kg/day of primaquine for 14 days in glucose-6-phosphate dehydrogenase normal patients of all ages. However, for many anti-malarial drugs, including primaquine, there is evidence that children have lower exposures than adults for the same weight-adjusted dose. The aim of the study was to develop 14-day weight-based and age-based primaquine regimens against high-frequency relapsing tropical P. vivax.
METHODS
The recommended adult target dose of 0.5 mg/kg/day (30 mg in a 60 kg patient) is highly efficacious against tropical P. vivax and was assumed to produce optimal drug exposure. Primaquine doses were calculated using allometric scaling to derive a weight-based primaquine regimen over a weight range from 5 to 100 kg. Growth curves were constructed from an anthropometric database of 53,467 individuals from the Greater Mekong Subregion (GMS) to define weight-for-age relationships. The median age associated with each weight was used to derive an age-based dosing regimen from the weight-based regimen.
RESULTS
The proposed weight-based regimen has 5 dosing bands: (i) 5-7 kg, 5 mg, resulting in 0.71-1.0 mg/kg/day; (ii) 8-16 kg, 7.5 mg, 0.47-0.94 mg/kg/day; (iii) 17-40 kg, 15 mg, 0.38-0.88 mg/kg/day; (iv) 41-80 kg, 30 mg, 0.37-0.73 mg/kg/day; and (v) 81-100 kg, 45 mg, 0.45-0.56 mg/kg/day. The corresponding age-based regimen had 4 dosing bands: 6-11 months, 5 mg, 0.43-1.0 mg/kg/day; (ii) 1-5 years, 7.5 mg, 0.35-1.25 mg/kg/day; (iii) 6-14 years, 15 mg, 0.30-1.36 mg/kg/day; and (iv) ≥ 15 years, 30 mg, 0.35-1.07 mg/kg/day.
CONCLUSION
The proposed weight-based regimen showed less variability around the primaquine dose within each dosing band compared to the age-based regimen and is preferred. Increased dose accuracy could be achieved by additional dosing bands for both regimens. The age-based regimen might not be applicable to regions outside the GMS, which must be based on local anthropometric data. Pharmacokinetic data in small children are needed urgently to inform the proposed regimens.
Journal Article > ResearchFull Text
PLOS One. 2021 November 19; Volume 16 (Issue 11); e0260096.; DOI:10.1371/journal.pone.0260096
Burtscher D, Van den Bergh R, Nasim M, Mahama G, Au S, et al.
PLOS One. 2021 November 19; Volume 16 (Issue 11); e0260096.; DOI:10.1371/journal.pone.0260096
BACKGROUND
Antibiotic resistance is a growing public health threat. In Afghanistan, high levels of indiscriminate antibiotic use exist, and healthcare programmes are not informed by understanding of local attitudes towards rational antibiotic use. Médecins Sans Frontières is an international non-governmental organization providing healthcare services to the Ahmad Shah Baba (ASB) District Hospital in Kabul, Afghanistan, since 2009. This mixed-methods study aimed to explore the perceptions and attitudes toward antibiotics among patients, prescribers, and pharmacists in the ASB District hospital outpatient department.
METHODS AND FINDINGS
Knowledge of antibiotics including their purpose and function, how and why they are used, and drivers for choice of antibiotic was examined at patient, prescriber, and provider-level. The first phase of the study, an exploratory qualitative component using an interpretative approach, was used to inform the second phase, a structured survey. Thirty-six interviews were conducted with 39 participants (21 patients or caretakers and 18 hospital health workers). Three hundred and fifty-one (351) patients and caretakers completed the second phase, the structured survey. This study found that poor knowledge of antibiotics and antibiotic resistance is a driving factor for inappropriate use of antibiotics. Participant perceptions of living in a polluted environment drove the high demand and perceived ‘need’ for antibiotics: patients, doctors and pharmacists alike consider dirty and dusty living conditions as causes of ‘disease’ in the body, requiring antibiotics to ‘clean’ and ‘strengthen’ it.
CONCLUSIONS
Findings highlight the need for strategies to improve awareness and knowledge of the general public, improve practice of doctors and pharmacists, regulate antibiotic dispensing in private pharmacies, and implement antibiotic stewardship in hospitals.
Antibiotic resistance is a growing public health threat. In Afghanistan, high levels of indiscriminate antibiotic use exist, and healthcare programmes are not informed by understanding of local attitudes towards rational antibiotic use. Médecins Sans Frontières is an international non-governmental organization providing healthcare services to the Ahmad Shah Baba (ASB) District Hospital in Kabul, Afghanistan, since 2009. This mixed-methods study aimed to explore the perceptions and attitudes toward antibiotics among patients, prescribers, and pharmacists in the ASB District hospital outpatient department.
METHODS AND FINDINGS
Knowledge of antibiotics including their purpose and function, how and why they are used, and drivers for choice of antibiotic was examined at patient, prescriber, and provider-level. The first phase of the study, an exploratory qualitative component using an interpretative approach, was used to inform the second phase, a structured survey. Thirty-six interviews were conducted with 39 participants (21 patients or caretakers and 18 hospital health workers). Three hundred and fifty-one (351) patients and caretakers completed the second phase, the structured survey. This study found that poor knowledge of antibiotics and antibiotic resistance is a driving factor for inappropriate use of antibiotics. Participant perceptions of living in a polluted environment drove the high demand and perceived ‘need’ for antibiotics: patients, doctors and pharmacists alike consider dirty and dusty living conditions as causes of ‘disease’ in the body, requiring antibiotics to ‘clean’ and ‘strengthen’ it.
CONCLUSIONS
Findings highlight the need for strategies to improve awareness and knowledge of the general public, improve practice of doctors and pharmacists, regulate antibiotic dispensing in private pharmacies, and implement antibiotic stewardship in hospitals.