Stakeholder perceptions on the deployment of multiple first-line therapies for uncomplicated malaria: a qualitative study in the health district of Kaya, Burkina Faso

BACKGROUND: In Burkina Faso, malaria remains the first cause of medical consultation and hospitalization in health centres. First-line case management of malaria in the country's health facilities is based on the use of artemisinin-based combination therapy (ACT). To optimize the use of these anti-malarial drugs in the perspective of mitigating the emergence of artemisinin resistance, which is a serious threat to malaria control and elimination, a pilot programme using multiple first-line therapies (MFTs) [three artemisinin-based combinations-pyronaridine-artesunate, dihydroartemisinin-piperaquine and artemether-lumefantrine] has been designed for implementation. As the success of this MFT pilot programme depends on the perceptions of key stakeholders in the health system and community members, the study aimed to assess their perceptions on the implementation of this strategy. METHODS: Semi-structured interviews, including 27 individual in-depth interviews and 41 focus groups discussions, were conducted with key stakeholders including malaria control policymakers and implementers, health system managers, health workers and community members. Volunteers from targets stakeholder groups were randomly selected. All interviews were recorded, transcribed and translated. Content analysis was performed using the qualitative software programme QDA Miner. RESULTS: The interviews revealed a positive perception of stakeholders on the implementation of the planned MFT programme. They saw the strategy as an opportunity to strengthen the supply of anti-malarial drugs and improve the management of fever and malaria. However, due to lack of experience with the products, health workers and care givers expressed some reservations about the effectiveness and side-effect profiles of the two anti-malarial drugs included as first-line therapy in the MFT programme (pyronaridine-artesunate, dihydroartemisinin-piperaquine). Questions were raised about the appropriateness of segmenting the population into three groups and assigning a specific drug to each group. CONCLUSION: The adherence of both populations and key stakeholders to the MFT implementation strategy will likely depend on the efficacy of the proposed drugs, the absence of, or low frequency of, side-effects, the cost of drugs and availability of the different combinations

Feasibility and acceptability of a strategy deploying multiple first-line artemisinin-based combination therapies for uncomplicated malaria in the health district of Kaya, Burkina Faso

(1) Background: Effective malaria case management relies on World Health Organization (WHO) recommended artemisinin-based combination therapies (ACTs), but partial resistance to artemisinin has emerged and is spreading, threatening malaria control and elimination efforts. The strategy of deploying multiple first-line therapies (MFT) may help mitigate this threat and extend the therapeutic life of current ACTs. (2) Methods: A district-wide pilot quasi-experimental study was conducted, deploying three different ACTs at the public health facility (PHF) level for uncomplicated malaria treatment from December 2019 to December 2020 in the health district (HD) of Kaya, Burkina Faso. Mixed methods, including household and health facility-based quantitative and qualitative surveys, were used to evaluate the pilot programme. (3) Results: A total of 2008 suspected malaria patients were surveyed at PHFs, of which 79.1% were tested by rapid diagnostic test (RDT) with 65.5% positivity rate. In total, 86.1% of the confirmed cases received the appropriate ACT according to the MFT strategy. The adherence level did not differ by study segment (p = 0.19). Overall, the compliance level of health workers (HWs) with MFT strategy was 72.7% (95% CI: 69.7-75.5). The odds of using PHF as the first source of care increased after the intervention (aOR = 1.6; 95% CI, 1.3-1.9), and the reported adherence to the 3-day treatment regimen was 82.1%; (95% CI: 79.6-84.3). Qualitative results showed a high acceptance of the MFT strategy with positive opinions from all stakeholders. (4) Conclusions: Implementing an MFT strategy is operationally feasible and acceptable by stakeholders in the health systems in Burkina Faso. This study provides evidence to support the simultaneous use of multiple first-line artemisinin combination therapies in malaria-endemic countries such as Burkina Faso

Attitudes, practices, and determinants of community care-seeking behaviours for fever/malaria episodes in the context of the implementation of multiple first-line therapies for uncomplicated malaria in the health district of Kaya, Burkina Faso

BACKGROUND: Malaria case management relies on World Health Organization (WHO)-recommended artemisinin-based combination therapy (ACT), and a continuous understanding of local community knowledge, attitudes, and practices may be a great support for the success of malaria disease control efforts. In this context, this study aimed to identify potential facilitators or barriers at the community level to inform a health district-wide implementation of multiple first-line therapies (MFT) as a new strategy for uncomplicated malaria case management. METHODS: A community-based cross-sectional study using a mixed-method design was carried out from November 2018 to February 2019, in the health district (HD) of Kaya in Burkina Faso. Quantitative data were collected using a standardized questionnaire from 1394 individuals who had fever/malaria episodes four weeks prior to the survey. In addition, 23 focus group discussions (FGDs) were conducted targeting various segments of the community. Logistic regression models were used to assess the predictors of community care-seeking behaviours. RESULTS: Overall, 98% (1366/1394) of study participants sought advice or treatment, and 66.5% did so within 24 h of fever onset. 76.4% of participants preferred to seek treatment from health centres as the first recourse to care, 5.8% were treated at home with remaining drug stock, and 2.3% preferred traditional healers. Artemether-lumefantrine (AL) was by far the most used anti-malarial drug (98.2%); reported adherence to the 3-day treatment regimen was 84.3%. Multivariate analysis identified less than 5 km distance travelled for care (AOR = 2.7; 95% CI 2.1-3.7) and education/schooling (AOR = 1.8; 95% CI 1.3-2.5) as determinants of prompt care-seeking for fever. Geographical proximity (AOR = 1.5, 95% CI 1.2-2.1), having a child under five (AOR = 4.6, 95% CI 3.2-6.7), being pregnant (AOR = 6.5, 95% CI 1.9-22.5), and living in an urban area (AOR = 2.8, 95% CI 1.8-4.2) were significant predictors for visiting health centres. The FGDs showed that participants had good knowledge about malaria symptoms, prevention tools, and effective treatment. Behaviour change regarding malaria treatment and free medication for children under five were the main reasons for participants to seek care at health centres. CONCLUSIONS: The study showed appropriate knowledge about malaria and positive community care-seeking behaviour at health centres for fever/malaria episodes. This could potentially facilitate the implementation of a MFT pilot programme in the district. CLINICALTRIALS: gov Identifier: NCT04265573

Refining adjuvant treatment in endometrial cancer based on molecular features: the RAINBO clinical trial program

Background The endometrial cancer molecular classification has been integrated into the 2020 World Health Organization (WHO) diagnostic classification and European treatment guidelines, and provides direction towards more effective and less toxic adjuvant treatment strategies for women with endometrial cancer. Primary objective(s) The RAINBO program of clinical trials will investigate four molecular class-directed adjuvant treatment strategies following surgical resection to either increase cure rates through the addition of novel targeted therapies or safely reduce toxicity and improve quality of life through treatment de-escalation. Study hypothesis Molecular-directed adjuvant treatment strategies will improve clinical outcomes and reduce toxicity of unwarranted therapies in women with endometrial cancer. The overarching and translational research RAINBO program will advance knowledge of predictive and prognostic (bio)markers that will improve prognostication and treatment allocation. Trial design The RAINBO program is a platform of four international clinical trials and an overarching research program. The randomized phase III p53abn-RED trial for women with invasive stage I-III p53abn endometrial cancer compares adjuvant chemoradiation followed by olaparib for 2 years with adjuvant chemoradiation alone. The randomized phase III MMRd-GREEN trial for women with stage II (with lymphovascular space invasion (LVSI)) or stage III mismatch repair-deficient (MMRd) endometrial cancer compares adjuvant radiotherapy with concurrent and adjuvant durvalumab for 1 year to radiotherapy alone. The randomized phase III NSMP-ORANGE trial is a treatment de-escalation trial for women with estrogen receptor positive stage II (with LVSI) or stage III no specific molecular profile (NSMP) endometrial cancer comparing radiotherapy followed by progestin for 2 years to adjuvant chemoradiation. The POLEmut-BLUE trial is a phase II trial in which the safety of de-escalation of adjuvant therapy is investigated for women with stage I-III POLEmut endometrial cancer: no adjuvant therapy for lower-risk disease and no adjuvant therapy or radiotherapy alone for higher-risk disease. The overarching RAINBO program will combine data and tumor material of all participants to perform translational research and evaluate molecular class-based adjuvant therapy in terms of efficacy, toxicity, quality of life, and cost-utility. Major inclusion/exclusion criteria Inclusion criteria include a histologically confirmed diagnosis of endometrial cancer treated by hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy or sentinel lymph node biopsy, with no macroscopic residual disease after surgery and no distant metastases, and molecular classification according to the WHO 2020 algorithm. Primary endpoint(s) Recurrence-free survival at 3 years in the p53abn-RED, MMRd-GREEN, and NSMP-ORANGE trials and pelvic recurrence at 3 years in the POLEmut-BLUE trial. Sample size The p53abn-RED trial will include 554 patients, the MMRd-GREEN trial 316, the NSMP-ORANGE trial 600, and the POLEmut-BLUE trial 145 (120 for lower-risk disease and approximately 25 for higher-risk disease). The overarching research program will pool the four sub-trials resulting in a total sample size of around 1600. Estimated dates for completing accrual and presenting resultsThe four clinical trials will have different completion dates; main results are expected from 2028