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

Intermittent preventive treatment of malaria provides substantial protection against malaria in children already protected by an insecticide-treated bednet in Burkina Faso: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Intermittent preventive treatment of malaria in children (IPTc) is a promising new approach to the control of malaria in areas of seasonal malaria transmission but it is not known if IPTc adds to the protection provided by an insecticide-treated net (ITN). METHODS AND FINDINGS: An individually randomised, double-blind, placebo-controlled trial of seasonal IPTc was conducted in Burkina Faso in children aged 3 to 59 months who were provided with a long-lasting insecticide-treated bednet (LLIN). Three rounds of treatment with sulphadoxine pyrimethamine plus amodiaquine or placebos were given at monthly intervals during the malaria transmission season. Passive surveillance for malaria episodes was established, a cross-sectional survey was conducted at the end of the malaria transmission season, and use of ITNs was monitored during the intervention period. Incidence rates of malaria were compared using a Cox regression model and generalized linear models were fitted to examine the effect of IPTc on the prevalence of malaria infection, anaemia, and on anthropometric indicators. 3,052 children were screened and 3,014 were enrolled in the trial; 1,505 in the control arm and 1,509 in the intervention arm. Similar proportions of children in the two treatment arms were reported to sleep under an LLIN during the intervention period (93%). The incidence of malaria, defined as fever or history of fever with parasitaemia ≥ 5,000/µl, was 2.88 (95% confidence interval [CI] 2.70-3.06) per child during the intervention period in the control arm versus 0.87 (95% CI 0.78-0.97) in the intervention arm, a protective efficacy (PE) of 70% (95% CI 66%-74%) (p<0.001). There was a 69% (95% CI 6%-90%) reduction in incidence of severe malaria (p = 0.04) and a 46% (95% CI 7%-69%) (p = 0.03) reduction in the incidence of all-cause hospital admissions. IPTc reduced the prevalence of malaria infection at the end of the malaria transmission season by 73% (95% CI 68%-77%) (p<0.001) and that of moderately severe anaemia by 56% (95% CI 36%-70%) (p<0.001). IPTc reduced the risks of wasting (risk ratio [RR] = 0.79; 95% CI 0.65-1.00) (p = 0.05) and of being underweight (RR = 0.84; 95% CI 0.72-0.99) (p = 0.03). Children who received IPTc were 2.8 (95% CI 2.3-3.5) (p<0.001) times more likely to vomit than children who received placebo but no drug-related serious adverse event was recorded. CONCLUSIONS: IPT of malaria provides substantial protection against malaria in children who sleep under an ITN. There is now strong evidence to support the integration of IPTc into malaria control strategies in areas of seasonal malaria transmission. TRIAL REGISTRATION: ClinicalTrials.govNCT00738946. Please see later in the article for the Editors' Summary

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

Molecular Markers for Sensitive Detection of Plasmodium falciparum Asexual Stage Parasites and their Application in a Malaria Clinical Trial.

Plasmodium falciparum parasite life stages respond differently to antimalarial drugs. Sensitive stage-specific molecular assays may help to examine parasite dynamics at microscopically detectable and submicroscopic parasite densities in epidemiological and clinical studies. In this study, we compared the performance of skeleton-binding protein 1 (SBP1), ring-infected erythrocyte surface antigen, Hyp8, ring-exported protein 1 (REX1), and PHISTb mRNA for detecting ring-stage trophozoite-specific transcripts using quantitative reverse transcriptase polymerase chain reaction. Markers were tested on tightly synchronized in vitro parasites and clinical trial samples alongside established markers of parasite density (18S DNA and rRNA) and gametocyte density (Pfs25 mRNA). SBP1 was the most sensitive marker but showed low-level expression in mature gametocytes. Novel markers REX1 and PHISTb showed lower sensitivity but higher specificity for ring-stage trophozoites. Using in vivo clinical trial samples from gametocyte-negative patients, we observed evidence of persisting trophozoite transcripts for at least 14 days postinitiation of treatment. It is currently not clear if these transcripts represent viable parasites that may have implications for clinical treatment outcome or transmission potential

Estimating the burden of iron deficiency among African children

Background Iron deficiency (ID) is a major public health burden in African children and accurate prevalence estimates are important for effective nutritional interventions. However, ID may be incorrectly estimated in Africa because most measures of iron status are altered by inflammation and infections such as malaria. Through the current study, we have assessed different approaches to the prediction of iron status and estimated the burden of ID in African children. Methods We assayed iron and inflammatory biomarkers in 4853 children aged 0–8 years from Kenya, Uganda, Burkina Faso, South Africa, and The Gambia. We described iron status and its relationship with age, sex, inflammation, and malaria parasitemia. We defined ID using the WHO guideline (ferritin < 12 μg/L or < 30 μg/L in the presence of inflammation in children < 5 years old or < 15 μg/L in children ≥ 5 years old). We compared this with a recently proposed gold standard, which uses regression-correction for ferritin levels based on the relationship between ferritin levels, inflammatory markers, and malaria. We further investigated the utility of other iron biomarkers in predicting ID using the inflammation and malaria regression-corrected estimate as a gold standard. Results The prevalence of ID was highest at 1 year of age and in male infants. Inflammation and malaria parasitemia were associated with all iron biomarkers, although transferrin saturation was least affected. Overall prevalence of WHO-defined ID was 34% compared to 52% using the inflammation and malaria regression-corrected estimate. This unidentified burden of ID increased with age and was highest in countries with high prevalence of inflammation and malaria, where up to a quarter of iron-deficient children were misclassified as iron replete. Transferrin saturation < 11% most closely predicted the prevalence of ID according to the regression-correction gold standard. Conclusions The prevalence of ID is underestimated in African children when defined using the WHO guidelines, especially in malaria-endemic populations, and the use of transferrin saturation may provide a more accurate approach. Further research is needed to identify the most accurate measures for determining the prevalence of ID in sub-Saharan Africa

Novel Insights Into the Protective Role of Hemoglobin S and C Against Plasmodium falciparum Parasitemia.

Although hemoglobin S (HbS) and hemoglobin C (HbC) are well known to protect against severe Plasmodium falciparum malaria, conclusive evidence on their role against infection has not yet been obtained. Here we show, in 2 populations from Burkina Faso (2007-2008), that HbS is associated with a 70% reduction of harboring P. falciparum parasitemia at the heterozygous state (odds ratio [OR] for AS vs AA, 0.27; 95% confidence interval [CI], .11-.66; P = .004). There is no evidence of protection for HbC in the heterozygous state (OR for AC vs AA, 1.49; 95% CI, .69-3.21; P = .31), whereas protection even higher than that observed with AS is observed in the homozygous and double heterozygous states (OR for CC + SC vs AA, 0.04; 95% CI, .01-.29; P = .002). The abnormal display of parasite-adhesive molecules on the surface of HbS and HbC infected erythrocytes, disrupting the pathogenic process of sequestration, might displace the parasite from the deep to the peripheral circulation, promoting its elimination at the spleen level