| 1. |
- Adjuik, Martin A., et al.
(författare)
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The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria : a meta-analysis of individual patient data
- 2015
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Methods: Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. Results: Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated with a 3.5-fold greater risk of recrudescence by day 28 (adjusted hazard ratio, AHR = 3.51 [95% CI: 2.02-6.12], P < 0.001) compared to FDC, and treatment with loose NFDC-30 was associated with a higher risk of recrudescence at only three sites. Conclusions: There was substantial variation in the total dose of amodiaquine administered in different AS-AQ combination regimens. Fixed dose AS-AQ combinations ensure optimal dosing and provide higher antimalarial treatment efficacy than the loose individual tablets in all age categories.
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| 2. |
- Abdelmagid, Nada, et al.
(författare)
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The Governance of Childhood Vaccination Services in Crisis Settings : A Scoping Review
- 2023
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Ingår i: Vaccines. - : MDPI. - 2076-393X. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- The persistence of inadequate vaccination in crisis-affected settings raises concerns about decision making regarding vaccine selection, timing, location, and recipients. This review aims to describe the key features of childhood vaccination intervention design and planning in crisis-affected settings and investigate how the governance of childhood vaccination is defined, understood, and practised. We performed a scoping review of 193 peer-reviewed articles and grey literature on vaccination governance and service design and planning. We focused on 41 crises between 2010 and 2021. Following screening and data extraction, our analysis involved descriptive statistics and applying the governance analysis framework to code text excerpts, employing deductive and inductive approaches. Most documents related to active outbreaks in conflict-affected settings and to the mass delivery of polio, cholera, and measles vaccines. Information on vaccination modalities, target populations, vaccine sources, and funding was limited. We found various interpretations of governance, often implying hierarchical authority and regulation. Analysis of governance arrangements suggests a multi-actor yet fragmented governance structure, with inequitable actor participation, ineffective actor collaboration, and a lack of a shared strategic vision due to competing priorities and accountabilities. Better documentation of vaccination efforts during emergencies, including vaccination decision making, governance, and planning, is needed. We recommend empirical research within decision-making spaces.
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| 3. |
- Allison, Lauren E, et al.
(författare)
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A Systematic Review of Vaccination Guidance for Humanitarian Responses
- 2023
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Ingår i: Vaccines. - : MDPI. - 2076-393X. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Delivering vaccines in humanitarian response requires rigourous and continuous analysis of evidence. This systematic review mapped the normative landscape of vaccination guidance on vaccine-preventable diseases in crisis-affected settings. Guidance published between 2000 and 2022 was searched for, in English and French, on websites of humanitarian actors, Google, and Bing. Peer-reviewed database searches were performed in Global Health and Embase. Reference lists of all included documents were screened. We disseminated an online survey to professionals working in vaccination delivery in humanitarian contexts. There was a total of 48 eligible guidance documents, including technical guidance (n = 17), descriptive guidance (n = 16), operational guidance (n = 11), evidence reviews (n = 3), and ethical guidance (n = 1). Most were World Health Organization documents (n = 21) targeting children under 5 years of age. Critical appraisal revealed insufficient inclusion of affected populations and limited rigour in guideline development. We found limited information on vaccines including, yellow fever, cholera, meningococcal, hepatitis A, and varicella, as well as human papilloma virus (HPV). There is a plethora of vaccination guidance for vaccine-preventable diseases in humanitarian contexts. However, gaps remain in the critical and systematic inclusion of evidence, inclusion of the concept of "zero-dose" children and affected populations, ethical guidance, and specific recommendations for HPV and non-universally recommended vaccines, which must be addressed.
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| 4. |
- Bile, Ahmed Said, et al.
(författare)
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Assessing Vaccination Delivery Strategies for Zero-Dose and Under-Immunized Children in the Fragile Context of Somalia
- 2024
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Ingår i: Vaccines. - : MDPI. - 2076-393X. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Somalia is one of 20 countries in the world with the highest numbers of zero-dose children. This study aims to identify who and where zero-dose and under-vaccinated children are and what the existing vaccine delivery strategies to reach zero-dose children in Somalia are. This qualitative study was conducted in three geographically diverse regions of Somalia (rural/remote, nomadic/pastoralists, IDPs, and urban poor population), with government officials and NGO staff (n = 17), and with vaccinators and community members (n = 52). The data were analyzed using the GAVI Vaccine Alliance IRMMA framework. Nomadic populations, internally displaced persons, and populations living in remote and Al-shabaab-controlled areas are three vulnerable and neglected populations with a high proportion of zero-dose children. Despite the contextual heterogeneity of these population groups, the lack of targeted, population-specific strategies and meaningful engagement of local communities in the planning and implementation of immunization services is problematic in effectively reaching zero-dose children. This is, to our knowledge, the first study that examines vaccination strategies for zero-dose and under-vaccinated populations in the fragile context of Somalia. Evidence on populations at risk of vaccine-preventable diseases and barriers to vital vaccination services remain critical and urgent, especially in a country like Somalia with complex health system challenges.
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| 5. |
- Venkatesan, Meera, et al.
(författare)
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Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes : parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine.
- 2014
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Ingår i: The American journal of tropical medicine and hygiene. - : American Society of Tropical Medicine and Hygiene. - 1476-1645 .- 0002-9637. ; 91:4, s. 833-43
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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