Scaling up malaria elimination management and leadership: a pilot in three provinces in Zimbabwe, 2016-2018

BACKGROUND: Focus for improved malaria programme performance is often placed on the technical challenges, while operational issues are neglected. Many of the operational challenges that inhibit malaria programme effectiveness can be addressed by improving communication and coordination, increasing accountability, maintaining motivation, providing adequate training and supervision, and removing bureaucratic silos. METHODS: A programme of work was piloted in Zimbabwe with one malaria eliminating province, Matabeleland South in 2016-2017, and scaled up to include two other provinces, Matabeleland North and Midlands, in 2017-2018. The intervention included participatory, organization development and quality improvement methods. RESULTS: Workshop participants in Matabeleland South reported an improvement in data management. In Matabeleland North, motivation among nurses improved as they gained confidence in case management from training, and overall staff morale improved. There was also an improvement in data quality and data sharing. In Midlands, the poorly performing district was motivated to improve, and both participating districts became more goal-oriented. They also became more focused on monitoring their data regularly. Participants from all provinces reported having gained skills in listening, communicating, facilitating discussions, and making presentations. Participation in the intervention changed the mindset of malaria programme staff, increasing ownership and accountability, and empowering them to identify and solve problems, make decisions, and act within their sphere of influence, elevating challenges when appropriate. CONCLUSIONS: This pilot demonstrates that a participatory, organization development and quality improvement approach has broad ranging effects, including improving local delivery of interventions, tailoring strategies to target specific populations, finding efficiencies in the system that could not be found using the traditional top-down approach, and improving motivation and communication between different cadres of health workers. Scale-up of this simple model can be achieved and benefits sustained over time if the process is imbedded into the programme with the training of health staff who can serve as management improvement coaches. Methods to improve operational performance that are scalable at the district level are urgently needed: this approach is a possible tactic that can significantly contribute to the achievement of global malaria eradication goals

Examining the human infectious reservoir for Plasmodium falciparum malaria in areas of differing transmission intensity.

A detailed understanding of the human infectious reservoir is essential for improving malaria transmission-reducing interventions. Here we report a multi-regional assessment of population-wide malaria transmission potential based on 1209 mosquito feeding assays in endemic areas of Burkina Faso and Kenya. Across both sites, we identified 39 infectious individuals. In high endemicity settings, infectious individuals were identifiable by research-grade microscopy (92.6%; 25/27), whilst one of three infectious individuals in the lowest endemicity setting was detected by molecular techniques alone. The percentages of infected mosquitoes in the different surveys ranged from 0.05 (4/7716) to 1.6% (121/7749), and correlate positively with transmission intensity. We also estimated exposure to malaria vectors through genetic matching of blood from 1094 wild-caught bloodfed mosquitoes with that of humans resident in the same houses. Although adults transmitted fewer parasites to mosquitoes than children, they received more mosquito bites, thus balancing their contribution to the infectious reservoir

Task-oriented evaluation of electronic medical records systems: development and validation of a questionnaire for physicians

BACKGROUND: Evaluation is a challenging but necessary part of the development cycle of clinical information systems like the electronic medical records (EMR) system. It is believed that such evaluations should include multiple perspectives, be comparative and employ both qualitative and quantitative methods. Self-administered questionnaires are frequently used as a quantitative evaluation method in medical informatics, but very few validated questionnaires address clinical use of EMR systems. METHODS: We have developed a task-oriented questionnaire for evaluating EMR systems from the clinician's perspective. The key feature of the questionnaire is a list of 24 general clinical tasks. It is applicable to physicians of most specialties and covers essential parts of their information-oriented work. The task list appears in two separate sections, about EMR use and task performance using the EMR, respectively. By combining these sections, the evaluator may estimate the potential impact of the EMR system on health care delivery. The results may also be compared across time, site or vendor. This paper describes the development, performance and validation of the questionnaire. Its performance is shown in two demonstration studies (n = 219 and 80). Its content is validated in an interview study (n = 10), and its reliability is investigated in a test-retest study (n = 37) and a scaling study (n = 31). RESULTS: In the interviews, the physicians found the general clinical tasks in the questionnaire relevant and comprehensible. The tasks were interpreted concordant to their definitions. However, the physicians found questions about tasks not explicitly or only partially supported by the EMR systems difficult to answer. The two demonstration studies provided unambiguous results and low percentages of missing responses. In addition, criterion validity was demonstrated for a majority of task-oriented questions. Their test-retest reliability was generally high, and the non-standard scale was found symmetric and ordinal. CONCLUSION: This questionnaire is relevant for clinical work and EMR systems, provides reliable and interpretable results, and may be used as part of any evaluation effort involving the clinician's perspective of an EMR system

SMA CARNI-VAL TRIAL PART II: A Prospective, Single-Armed Trial of L-Carnitine and Valproic Acid in Ambulatory Children with Spinal Muscular Atrophy

Multiple lines of evidence have suggested that valproic acid (VPA) might benefit patients with spinal muscular atrophy (SMA). The SMA CARNIVAL TRIAL was a two part prospective trial to evaluate oral VPA and l-carnitine in SMA children. Part 1 targeted non-ambulatory children ages 2–8 in a 12 month cross over design. We report here Part 2, a twelve month prospective, open-label trial of VPA and L-carnitine in ambulatory SMA children.This study involved 33 genetically proven type 3 SMA subjects ages 3–17 years. Subjects underwent two baseline assessments over 4–6 weeks and then were placed on VPA and L-carnitine for 12 months. Assessments were performed at baseline, 3, 6 and 12 months. Primary outcomes included safety, adverse events and the change at 6 and 12 months in motor function assessed using the Modified Hammersmith Functional Motor Scale Extend (MHFMS-Extend), timed motor tests and fine motor modules. Secondary outcomes included changes in ulnar compound muscle action potential amplitudes (CMAP), handheld dynamometry, pulmonary function, and Pediatric Quality of Life Inventory scores.Twenty-eight subjects completed the study. VPA and carnitine were generally well tolerated. Although adverse events occurred in 85% of subjects, they were usually mild and transient. Weight gain of 20% above body weight occurred in 17% of subjects. There was no significant change in any primary outcome at six or 12 months. Some pulmonary function measures showed improvement at one year as expected with normal growth. CMAP significantly improved suggesting a modest biologic effect not clinically meaningful.This study, coupled with the CARNIVAL Part 1 study, indicate that VPA is not effective in improving strength or function in SMA children. The outcomes used in this study are feasible and reliable, and can be employed in future trials in SMA

Induction of Selective Blood-Tumor Barrier Permeability and Macromolecular Transport by a Biostable Kinin B1 Receptor Agonist in a Glioma Rat Model

Treatment of malignant glioma with chemotherapy is limited mostly because of delivery impediment related to the blood-brain tumor barrier (BTB). B1 receptors (B1R), inducible prototypical G-protein coupled receptors (GPCR) can regulate permeability of vessels including possibly that of brain tumors. Here, we determine the extent of BTB permeability induced by the natural and synthetic peptide B1R agonists, LysdesArg9BK (LDBK) and SarLys[dPhe8]desArg9BK (NG29), in syngeneic F98 glioma-implanted Fischer rats. Ten days after tumor inoculation, we detected the presence of B1R on tumor cells and associated vasculature. NG29 infusion increased brain distribution volume and uptake profiles of paramagnetic probes (Magnevist and Gadomer) at tumoral sites (T1-weighted imaging). These effects were blocked by B1R antagonist and non-selective cyclooxygenase inhibitors, but not by B2R antagonist and non-selective nitric oxide synthase inhibitors. Consistent with MRI data, systemic co-administration of NG29 improved brain tumor delivery of Carboplatin chemotherapy (ICP-Mass spectrometry). We also detected elevated B1R expression in clinical samples of high-grade glioma. Our results documented a novel GPCR-signaling mechanism for promoting transient BTB disruption, involving activation of B1R and ensuing production of COX metabolites. They also underlined the potential value of synthetic biostable B1R agonists as selective BTB modulators for local delivery of different sized-therapeutics at (peri)tumoral sites

Dramatic Transcriptional Changes in an Intracellular Parasite Enable Host Switching between Plant and Insect

Phytoplasmas are bacterial plant pathogens that have devastating effects on the yields of crops and plants worldwide. They are intracellular parasites of both plants and insects, and are spread among plants by insects. How phytoplasmas can adapt to two diverse environments is of considerable interest; however, the mechanisms enabling the “host switching” between plant and insect hosts are poorly understood. Here, we report that phytoplasmas dramatically alter their gene expression in response to “host switching” between plant and insect. We performed a detailed characterization of the dramatic change that occurs in the gene expression profile of Candidatus Phytoplasma asteris OY-M strain (approximately 33% of the genes change) upon host switching between plant and insect. The phytoplasma may use transporters, secreted proteins, and metabolic enzymes in a host-specific manner. As phytoplasmas reside within the host cell, the proteins secreted from phytoplasmas are thought to play crucial roles in the interplay between phytoplasmas and host cells. Our microarray analysis revealed that the expression of the gene encoding the secreted protein PAM486 was highly upregulated in the plant host, which is also observed by immunohistochemical analysis, suggesting that this protein functions mainly when the phytoplasma grows in the plant host. Additionally, phytoplasma growth in planta was partially suppressed by an inhibitor of the MscL osmotic channel that is highly expressed in the plant host, suggesting that the osmotic channel might play an important role in survival in the plant host. These results also suggest that the elucidation of “host switching” mechanism may contribute to the development of novel pest controls