Two decades of molecular surveillance in Senegal reveal rapid changes in known drug resistance mutations over time.

BACKGROUND: Drug resistance in Plasmodium falciparum is a major threat to malaria control efforts. Pathogen genomic surveillance could be invaluable for monitoring current and emerging parasite drug resistance. METHODS: Data from two decades (2000-2020) of continuous molecular surveillance of P. falciparum parasites from Senegal were retrospectively examined to assess historical changes in malaria drug resistance mutations. Several known drug resistance markers and their surrounding haplotypes were profiled using a combination of single nucleotide polymorphism (SNP) molecular surveillance and whole genome sequence based population genomics. RESULTS: This dataset was used to track temporal changes in drug resistance markers whose timing correspond to historically significant events such as the withdrawal of chloroquine (CQ) and the introduction of sulfadoxine-pyrimethamine (SP) in 2003. Changes in the mutation frequency at Pfcrt K76T and Pfdhps A437G coinciding with the 2014 introduction of seasonal malaria chemoprevention (SMC) in Senegal were observed. In 2014, the frequency of Pfcrt K76T increased while the frequency of Pfdhps A437G declined. Haplotype-based analyses of Pfcrt K76T showed that this rapid increase was due to a recent selective sweep that started after 2014. DISCUSSION (CONCLUSION): The rapid increase in Pfcrt K76T is troubling and could be a sign of emerging amodiaquine (AQ) resistance in Senegal. Emerging AQ resistance may threaten the future clinical efficacy of artesunate-amodiaquine (ASAQ) and AQ-dependent SMC chemoprevention. These results highlight the potential of molecular surveillance for detecting rapid changes in parasite populations and stress the need to monitor the effectiveness of AQ as a partner drug for artemisinin-based combination therapy (ACT) and for chemoprevention.

Quality assessment of malaria microscopic diagnosis at the Aristide Le Dantec University Hospital of Dakar, Senegal, in 2020.

BACKGROUND: Following WHO guidelines, microscopy is the gold standard for malaria diagnosis in endemic countries. The Parasitology-Mycology laboratory (LPM) is the National Reference Laboratory and is currently undergoing ISO 15189 accreditation. In this context, we assessed the performance of the laboratory by confirming the reliability and the accuracy of results obtained in accordance with the requirements of the ISO 15189 standards. This study aimed to verify the method of microscopic diagnosis of malaria at the LPM, in the Aristide Le Dantec hospital (HALD) in Dakar, Senegal. METHODS: This is a validation/verification study conducted from June to August 2020. Twenty (20) microscopic slides of thick/thin blood smear with known parasite densities (PD) selected from the Cheick Anta Diop University malaria slide bank in Dakar were used for this assessment. Six (6) were used to assess microscopists' ability to determine PD and fourteen (14) slides were used for detection (positive vs negative) and identification of parasites. Four (4) LPM-HALD microscopists read and recorded their results on prepared sheets. Data analysis was done with Microsoft Excel 2010 software. RESULTS: A minimum threshold of 50% concordance was used for comparison. Of the twenty (20) slides read, 100% concordance was obtained on eight (8) detection (positive vs negative) slides. Four (4) out of the six (6) parasite density evaluation slides obtained a concordance of less than 50%. Thirteen (13) out of the fourteen (14) identification slides obtained a concordance greater than 50%. Only one (1) identification slide obtained zero agreement from the microscopists. For species identification a concordance greater than 80% was noted and the microscopists obtained scores between 0.20 and 0.4 on a scale of 0 to 1 for parasite density reading. The microscopists obtained 100% precision, sensitivity, specificity and both negative and positive predictive values. CONCLUSION: This work demonstrated that the microscopic method of malaria diagnosis used in the LPM/HALD is in accordance with the requirements of WHO and ISO 15189. Further training of microscopists may be needed to maintain competency.

Two decades of molecular surveillance in Senegal reveal changes in known drug resistance mutations associated with historical drug use and seasonal malaria chemoprevention.

Drug resistance in Plasmodium falciparum is a major threat to malaria control efforts. We analyzed data from two decades (2000-2020) of continuous molecular surveillance of P. falciparum parasite strains in Senegal to determine how historical changes in drug administration policy may have affected parasite evolution. We profiled several known drug resistance markers and their surrounding haplotypes using a combination of single nucleotide polymorphism (SNP) molecular surveillance and whole-genome sequence (WGS) based population genomics. We observed rapid changes in drug resistance markers associated with the withdrawal of chloroquine and introduction of sulfadoxine-pyrimethamine in 2003. We also observed a rapid increase in Pfcrt K76T and decline in Pfdhps A437G starting in 2014, which we hypothesize may reflect changes in resistance or fitness caused by seasonal malaria chemoprevention (SMC). Parasite populations evolve rapidly in response to drug use, and SMC preventive efficacy should be closely monitored.

Understanding drivers of stunting reduction in Nigeria from 2003 to 2018: a regression analysis.

Nigeria is a high burden country for stunting. Stunting reduction has been slow and characterized by unequal progress across the 36 states and federal capital territory of the country. This study aimed to assess the changes in prevalence of stunting and growth determinants from 2003 to 2018, identify factors that predicted the change in stunting, and project future stunting prevalence if these predicted determinants improve. Trend and linear decomposition analyses of growth outcomes and determinants were conducted using 2003, 2008, 2013, and 2018 Nigeria Demographic and Health Survey data. Pooled data included 57,507 children 0 to 59 months old. Findings show that stunting and severe stunting significantly reduced from 43 to 37% and 23% to 17%, respectively (p < 0.001), between 2003 and 2018. Disturbingly, height-for-age z-scores at birth significantly decreased, indicating risks of potential future stunting increase. Improvements in nine stunting determinants (maternal body mass index, maternal height, ≥ 4 antenatal care visits, health facility delivery, reduced child illnesses, asset index, maternal education, paternal education, and preceding birth interval) predicted stunting reductions in children 0-59 months. Few of these nine determinants improved in subpopulations with limited stunting progress. Intra-sectoral and multisectoral coordination were potentially inadequate; 12% of children had received all of three selected health sector interventions along a continuum of care and 6% had received all of six selected multisector interventions. Forward looking projections suggest that increased efforts to improve the nine predictors of stunting change can reduce under-five stunting in Nigeria to ≤ 27% in the short term. Supplementary Information: The online version contains supplementary material available at 10.1007/s12571-022-01279-8.

Stories of change in nutrition in Burkina Faso 1992-2018: a micro-level perspective.

Looking back at what has effectively improved nutrition may inform policy makers on how to accelerate progress to end all forms of malnutrition by 2030. As under-five stunting declined substantially in Burkina Faso, we analyzed its nutrition story at the micro-level. We conducted a regression-decomposition analysis to identify demographic and health drivers associated with change in height-for-age using longitudinal, secondary, nationally-representative data. We triangulated results with findings from semi-structured community interviews (n = 91) in two "model communities" with a history of large stunting reduction. We found that improvement in immunization coverage, assets accumulation and reduction in open defecation were associated with 23%, 10% and 6.1% of the improvement in height-for-age, respectively. Associations were also found with other education, family planning, health and WASH indicators. Model communities acknowledged progress in the coverage and quality of nutrition-specific and nutrition-sensitive sectoral programs co-located at the community level, especially those delivered through the health and food security sectors, though delivery challenges remained in a context of systemic poverty and persistent food insecurity. Burkina Faso's health sector's success in improving coverage of nutrition and healthcare programs may have contributed to improvements in child nutrition alongside other programmatic improvements in the food security, WASH and education sectors. Burkina Faso should continue to operationalize sectoral nutrition-sensitive policies into higher-quality programs at scale, building on its success stories such as vaccination. Community leverage gaps and data gaps need to be filled urgently to pressure for and monitor high coverage, quality delivery, and nutrition impact of agriculture, education, and WASH interventions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12571-022-01274-z.

How Denmark, England, Estonia, France, Germany, and the USA Pay for Variable, Specialized and Low Volume Care: A Cross-country Comparison of In-patient Payment Systems.

BACKGROUND: Diagnosis-related group (DRG)-based hospital payment can potentially be inadequately low (or high) for highly variable, highly specialized, and/or low volume care. DRG-based payment can be combined with other payment mechanisms to avoid unintended consequences of inadequate payment. The aim of this study was to analyze these other payment mechanisms for acute inpatient care across six countries (Germany, Denmark, England, Estonia, France, the United States [Medicare]). METHODS: Information was collected about elements excluded from DRG-based payment, the rationale for exclusions, and payment mechanisms complementing DRG-based payment. A conceptual framework was developed to systematically describe, visualise and compare payment mechanisms across countries. RESULTS: Results show that the complexity of exclusion mechanisms and associated additional payment components differ across countries. England and Germany use many different additional mechanisms, while there are only few exceptions from DRG-based payment in the Medicare program in the United States. Certain areas of care are almost always excluded (eg, certain areas of cancer care or specialized pediatrics). Denmark and England use exclusion mechanisms to steer service provision for highly complex patients to specialized providers. CONCLUSION: Implications for researchers and policy-makers include: (1) certain areas of care might be better excluded from DRG-based payment; (2) exclusions may be used to incentivize the concentration of highly specialized care at specialized institutions (as in Denmark or England); (3) researchers may apply our analytical framework to better understand the specific design features of DRG-based payment systems.

Impact of Competition Versus Centralisation of Hospital Care on Process Quality: A Multilevel Analysis of Breast Cancer Surgery in France.

BACKGROUND: The implications of competition among hospitals on care quality have been the subject of considerable debate. On one hand, economic theory suggests that when prices are regulated, quality will be increased in competitive markets. On the other hand, hospital mergers have been justified by the need to exploit cost advantages, and by evidence that hospital volume and care quality are related. METHODS: Based on patient-level data from two years (2005 and 2012) we track changes in market competition and treatment patterns in breast cancer surgery. We focus on technology adoption as a proxy of process quality and examine the likelihood of offering two innovative surgical procedures: immediate breast reconstruction (IBR), after mastectomy and sentinel lymph node biopsy (SLNB). We use an index of competition based on a multinomial logit model of hospital choice which is not subject to endogeneity bias, and estimate its impact on the propensity to receive IBR and SLNB by means of multilevel models taking into account both observable patient and hospital characteristics. RESULTS: The likelihood of receiving these procedures is significantly higher in hospitals located in more competitive markets. Yet, hospital volume remains a significant indicator of quality, therefore benefits of competition appear to be sensitive to the estimates of the impact of volume on care process. In France, the centralisation policy, with minimum activity thresholds, have contributed to improving breast cancer treatment between 2005 and 2012. CONCLUSION: Finding the right balance between costs and benefits of market competition versus concentration of hospital care supply is complex. We find that close to monopolistic markets do not encourage innovation and quality in cancer treatment, but highly competitive markets where many hospitals have very low activity volumes are also problematic because hospital quality is positively linked to patient volume.

Coherence for nutrition: insights from nutrition-relevant policies and programmes in Burkina Faso and Nigeria.

There is consensus that policy coherence is necessary for implementing effective and sustainable approaches to tackle malnutrition. We look at whether policies and programmes provide a coherent pathway to address nutrition priorities and if programmes are designed to deliver interventions aligned to the nutrition policy agenda in Nigeria and Burkina Faso. A systematic desk review was performed on nutrition-relevant policy and programme documents, obtained through grey literature searches and expert recommendations. We developed a framework with an impact pathway structure that includes five process steps, which was used to guide coding, data reduction and synthesis and structure the analysis. We assessed internal coherence along process steps within a given document and external coherence across process steps for explicitly linked policy/programme pairs. The majority of policies and programmes had partial internal coherence for both countries. The identification of relevant nutrition interventions to address challenges and reach objectives was the strongest connection within policies (16 out of 45 had complete coherence), while among programmes, the strongest connection was coverage indicators that measure interventions (9 out of 21 had complete coherence). Eight programmes explicitly referenced at least one nutrition-relevant policy, with a total of 16 linked policy/programme pairs (13 pairs for Burkina Faso and 3 for Nigeria) across health, nutrition, agriculture and social focus areas. However, none of the linked pairs were assessed to have complete external coherence, suggesting that priorities at the policy level are not fully realized nor translated at the programme level. This study offers a new approach for the assessment of policy and programme coherence and specifically examines policy and programme linkages. We conclude that improved leadership on country priority setting and better alignment for nutrition within and across sectors is needed to enhance the effectiveness of nutrition investments.

Impact on child acute malnutrition of integrating a preventive nutrition package into facility-based screening for acute malnutrition during well-baby consultation: A cluster-randomized controlled trial in Burkina Faso.

BACKGROUND: Community management of acute malnutrition (CMAM) is a highly efficacious approach for treating acute malnutrition (AM) in children who would otherwise be at significantly increased risk of mortality. In program settings, however, CMAM's effectiveness is limited because of low screening coverage of AM, in part because of the lack of perceived benefits for caregivers. In Burkina Faso, monthly screening for AM of children <2 years of age is conducted during well-baby consultations (consultation du nourrisson sain [CNS]) at health centers. We hypothesized that the integration of a preventive package including age-appropriate behavior change communication (BCC) on nutrition, health, and hygiene practices and a monthly supply of small-quantity lipid-based nutrient supplements (SQ-LNSs) to the monthly screening would increase AM screening and treatment coverage and decrease the incidence and prevalence of AM. METHODS AND FINDINGS: We used a cluster-randomized controlled trial and allocated 16 health centers to the intervention group and 16 to a comparison group. Both groups had access to standard CMAM and CNS services; caregivers in the intervention group also received age-appropriate monthly BCC and SQ-LNS for children >6 months of age. We used two study designs: (1) a repeated cross-sectional study of children 0-17 months old (n = 2,318 and 2,317 at baseline and endline 2 years later) to assess impacts on AM screening coverage, treatment coverage, and prevalence; (2) a longitudinal study of 2,113 children enrolled soon after birth and followed up monthly for 18 months to assess impacts on AM screening coverage, treatment coverage, and incidence. Data were analyzed as intent to treat. Level of significance for primary outcomes was α = 0.016 after adjustment for multiple testing. Children's average age was 8.8 ± 4.9 months in the intervention group and 8.9 ± 5.0 months in the comparison group at baseline and, respectively, 0.66 ± 0.32 and 0.67 ± 0.33 months at enrollment in the longitudinal study. Relative to the comparison group, the intervention group had significantly higher monthly AM screening coverage (cross-sectional study: +18 percentage points [pp], 95% CI 10-26, P < 0.001; longitudinal study: +23 pp, 95% CI 17-29, P < 0.001). There were no impacts on either AM treatment coverage (cross-sectional study: +8.0 pp, 95% CI 0.09-16, P = 0.047; longitudinal study: +7.7 pp, 95% CI -1.2 to 17, P = 0.090), AM incidence (longitudinal study: incidence rate ratio = 0.98, 95% CI 0.75-1.3, P = 0.88), or AM prevalence (cross-sectional study: -0.46 pp, 95% CI -4.4 to 3.5, P = 0.82). A study limitation is the referral of AM cases (for ethical reasons) by study enumerators as part of the monthly measurement in the longitudinal study that may have attenuated the detectable impact on AM treatment coverage. CONCLUSIONS: Adding a preventive package to CMAM delivered at health facilities in Burkina Faso increased participation in monthly AM screening, thus overcoming a major impediment to CMAM effectiveness. The lack of impact on AM treatment coverage and on AM prevalence and incidence calls for research to address the remaining barriers to uptake of preventive and treatment services at the health center and to identify and test complementary approaches to bring integrated preventive and CMAM services closer to the community while ensuring high-quality implementation and service delivery. TRIAL REGISTRATION: ClinicalTrials.gov NCT02245152.

Assessment of organizational readiness for e-health in a rehabilitation centre.

PURPOSE: The aims of this study were to assess organizational readiness for e-health among the staff of an out-patient rehabilitation centre and to identify the personal characteristics of potential users that may have influenced readiness. METHODS: A cross-sectional study was conducted with 137 clinicians, 28 managers, and 47 nonclinical staff in a rehabilitation centre in Montreal, Quebec, Canada. All participants completed a self-administered questionnaire assessing organizational readiness for e-health. The measure contained three subscales: Individual, Organizational and Technological. Data were also collected on the users' profile, use of technologies and typical response to new information. RESULTS: Generally, participants considered themselves ready to adopt e-health in their work (X = 73.8%, SD = 8.5) and they also had a favorable view of the technologies in place (X 73.8%, SD = 7.2). However, they perceived the center as being only moderately ready (X 66.6%, SD = 9.8) for e-health changes. Perceived workload and position/duties in the organization were found to have an impact on readiness for e-health. CONCLUSIONS: These results underscore the importance of addressing organizational readiness for change as a multidimensional concept. Based on these results, implementation strategies tailored to the specific profile of a rehabilitation organization were identified.