‘Working relationships’ across difference - a realist review of community engagement with malaria research

Background: Community engagement (CE) is increasingly accepted as a critical aspect of health research, because of its potential to make research more ethical, relevant and well implemented. While CE activities linked to health research have proliferated in Low and Middle Income Countries (LMICs), and are increasingly described in published literature, there is a lack of conceptual clarity around how engagement is understood to ‘work’, and the aims and purposes of engagement are varied and often not made explicit. Ultimately, the evidence base for engagement remains underdeveloped. Methods: To develop explanations for how and why CE with health research contributes to the pattern of outcomes observed in published literature, we conducted a realist review of CE with malaria research – a theory driven approach to evidence synthesis. Results: We found that community engagement relies on the development of provisional ‘working relationships’ across differences, primarily of wealth, power and culture. These relationships are rooted in interactions that are experienced as relatively responsive and respectful, and that bring tangible research related benefits. Contextual factors affecting development of working relationships include the facilitating influence of research organisation commitment to and resources for engagement, and constraining factors linked to the prevailing ‘dominant health research paradigm context’, such as: differences of wealth and power between research centres and local populations and health systems; histories of colonialism and vertical health interventions; and external funding and control of health research. Conclusions: The development of working relationships contributes to greater acceptance and participation in research by local stakeholders, who are particularly interested in research related access to health care and other benefits. At the same time, such relationships may involve an accommodation of some ethically problematic characteristics of the dominant health research paradigm, and thereby reproduce this paradigm rather than challenge it with a different logic of collaborative partnership.

Microbiota Variation Across Life Stages of European Field-Caught Anopheles atroparvus and During Laboratory Colonization: New Insights for Malaria Research

The potential use of bacteria for developing novel vector control approaches has awakened new interests in the study of the microbiota associated with vector species. To set a baseline for future malaria research, a high-throughput sequencing of the bacterial 16S ribosomal gene V3-V4 region was used to profile the microbiota associated with late-instar larvae, newly emerged females, and wild-caught females of a sylvan Anopheles atroparvus population from a former malaria transmission area of Spain. Field-acquired microbiota was then assessed in non-blood-fed laboratory-reared females from the second, sixth, and 10th generations. Diversity analyses revealed that bacterial communities varied and clustered differently according to origin with sylvan larvae and newly emerged females distributing closer to laboratory-reared females than to their field counterparts. Inter-sample variation was mostly observed throughout the different developmental stages in the sylvan population. Larvae harbored the most diverse bacterial communities; wild-caught females, the poorest. In the transition from the sylvan environment to the first time point of laboratory breeding, a significant increase in diversity was observed, although this did decline under laboratory conditions. Despite diversity differences between wild-caught and laboratory-reared females, a substantial fraction of the bacterial communities was transferred through transstadial transmission and these persisted over 10 laboratory generations. Differentially abundant bacteria were mostly identified between breeding water and late-instar larvae, and in the transition from wild-caught to laboratory-reared females from the second generation. Our findings confirmed the key role of the breeding environment in shaping the microbiota of An. atroparvus. Gram-negative bacteria governed the microbiota of An. atroparvus with the prevalence of proteobacteria. Pantoea, Thorsellia, Serratia, Asaia, and Pseudomonas dominating the microbiota associated with wild-caught females, with the latter two governing the communities of laboratory-reared females. A core microbiota was identified with Pseudomonas and Serratia being the most abundant core genera shared by all sylvan and laboratory specimens. Overall, understanding the microbiota composition of An. atroparvus and how this varies throughout the mosquito life cycle and laboratory colonization paves the way when selecting potential bacterial candidates for use in microbiota-based intervention strategies against mosquito vectors, thereby improving our knowledge of laboratory-reared An. atroparvus mosquitoes for research purposes.

Community Engagement for Malaria Elimination in the Greater Mekong Subregion: a Qualitative Study Among Malaria Researchers and Policymakers

IntroductionCommunity engagement has increasingly received attention in malaria research and program interventions, particularly as countries approach closer to malaria elimination. Although strategies and aspects of community engagement are constantly developing, little is known about how those who implement research or programs view community engagement. This article explores the perspectives of researchers and policy makers in the Greater Mekong Subregion (GMS) on community engagement for malaria control and elimination. MethodsSemi-structured interviews were conducted among 17 policymakers and 15 senior researchers working in the field of malaria. All interviews were audio-recorded and transcribed in English. Transcribed data were analyzed using deductive and inductive approach in QSR NVivo. Themes and sub-themes were generated. ResultsResearchers and policymakers emphasized the importance of community engagement in promoting participation in malaria research and interventions. Building trust with the community was seen as crucial. Respondents emphasized involving authority/leadership structures and highlighted the need for intense and participatory engagement. Geographic remoteness, social, cultural, and linguistic diversity were identified as barriers to meaningful engagement. Local staff were described as an essential ‘connect’ between researchers or policy makers and prospective participants. Sharing information with community members, using various strategies such as visualization of message including creative and participatory methods were highlighted. ConclusionsAs malaria continues to decline across the GMS, countries have set elimination goals. In this context, policy makers and researchers involved in malaria prevention and control in the region viewed community engagement as crucial for promoting participation in research or programmatic interventions. Given the difficulties of the “last mile” to elimination, sustained investment in community engagement is needed in isolated areas of the GMS where malaria transmission continues.

A portfolio of geographically distinct laboratory-adapted Plasmodium falciparum clones with consistent infection rates in Anopheles mosquitoes

Background The ability to culture Plasmodium falciparum continuously in vitro has enabled stable access to asexual and sexual parasites for malaria research. The portfolio of isolates has remained limited and research is still largely based on NF54 and its derived clone 3D7. Since 1978, isolates were collected and cryopreserved at Radboudumc from patients presenting at the hospital. Here, procedures are described for culture adaptation of asexual parasites, cloning and production of sexual stage parasites responsible for transmission (gametocytes) and production of oocysts in Anopheles mosquitoes. This study aimed to identify new culture-adapted transmissible P. falciparum isolates, originating from distinct geographical locations. Methods Out of a collection of 121 P. falciparum isolates stored in liquid nitrogen, 21 from different geographical origin were selected for initial testing. Isolates were evaluated for their ability to be asexually cultured in vitro, their gametocyte production capacity, and consistent generation of oocysts. Results Out of 21 isolates tested, twelve were excluded from further analysis due to lack of mature gametocyte production (n = 1) or generation of satisfactory numbers of oocysts in mosquitoes (n = 11). Nine isolates fulfilled selection criteria and were cloned by limiting dilution and retested. After cloning, one isolate was excluded for not showing transmission. The remaining eight isolates transmitted to Anopheles stephensi or Anopheles coluzzii mosquitoes and were categorized into two groups with a reproducible mean oocyst infection intensity above (n = 5) or below five (n = 3). Conclusions These new P. falciparum culture-adapted isolates with reproducible transmission to Anopheles mosquitoes are a valuable addition to the malaria research tool box. They can aid in the development of malaria interventions and will be particularly useful for those studying malaria transmission.

A Portfolio of Geographically Distinct Laboratory-adapted Plasmodium Falciparum Clones With Consistent Infection Rates in Anopheles Mosquitoes

BackgroundThe ability to culture P. falciparum continuously in vitro has enabled stable access to asexual and sexual parasites for malaria research. The portfolio of isolates has remained limited and research is still largely based on NF54 and its derived clone 3D7. Since 1978, isolates were collected and cryopreserved at Radboudumc from patients presenting at the hospital. Here, procedures are described for culture adaptation of asexual parasites, cloning and production of sexual stage parasites responsible for transmission (gametocytes) and production of oocysts in Anopheles mosquitoes. This study aimed to identify new culture adapted transmissible P. falciparum isolates, originating from distinct geographical locations.ResultsOut of a collection of 121 P. falciparum isolates stored in liquid nitrogen, 21 from different geographical origin were selected for initial testing. Isolates were evaluated for their ability to be asexually cultured in vitro, their gametocyte production capacity, and consistent generation of oocysts. Out of 21 isolates tested, twelve were excluded from further analysis due to lack of mature gametocyte production (n = 1) or generation of satisfactory numbers of oocysts in mosquitoes (n = 11). Nine isolates fulfilled selection criteria and were cloned by limiting dilution and retested. After cloning, one isolate was excluded for not showing transmission. The remaining eight isolates transmitted to A. stephensi or A. coluzzii mosquitoes and were categorized into two groups with a reproducible mean oocyst infection intensity above (n = 5) or below five (n = 3). ConclusionsThese new P. falciparum culture adapted isolates with reproducible transmission to Anopheles mosquitoes are a valuable addition to the malaria research tool box. They can aid in the development of malaria interventions and will be particularly useful for those studying malaria transmission.

Laboratory Detection of Malaria Antigens: a Strong Tool for Malaria Research, Diagnosis, and Epidemiology

The identification and characterization of proteins produced during human infection with Plasmodium spp. have guided the malaria community in research, diagnosis, epidemiology, and other efforts. Recently developed methods for the detection of these proteins (antigens) in the laboratory have provided new types of data that can inform the evaluation of malaria diagnostics, epidemiological investigations, and overall malaria control strategies.

Theory of change: Drama and arts-based community engagement for malaria research and elimination in Cambodia

Background: Across the Greater Mekong Sub-region, malaria persists in isolated communities along international borders. Arts and drama have been used to reach to communities in Cambodia to engage them in malaria research, prevention and control. The “Village Drama Against Malaria” (VDAM) project was conducted in north eastern and western Cambodia: Stung Treng; Battambang and Pailin provinces during 2016 to 2019. In total, VDAM reached 55 rural villages, 2,378 student participants and 43,502 audience members. Methods: This article presents the results of two stakeholder-led evaluation workshops in which participants collaboratively developed theories of change to better understand the potential and actual impact of arts and drama-based activities on malaria in these communities. The workshops had a particular focus on identifying areas for monitoring and evaluation so that impact can be measured. Workshop participants included village malaria workers, community leaders, professional and student drama performers, and representatives from the local health authorities and the national malaria control programme. Results: Five broad areas were identified as relevant for monitoring and evaluation: logistical and practical challenges; embeddedness and reach of engagement; health knowledge and confidence of young people; effectiveness of communications; impact on malaria. These areas align well with the monitoring and evaluation conducted to date and point to additional opportunities for data collection. Conclusions: The findings from these workshops will inform future engagement strategies, for example, we may engage a smaller number of young people but over a longer period and more in-depth.

Research supporting malaria control and elimination in China over four decades: a bibliometric analysis of academic articles published in chinese from 1980 to 2019

Background China has accumulated considerable experience in malaria control and elimination over the past decades. Many research papers have been published in Chinese journals. This study intends to describe the development and experience of malaria control and elimination in China by quantitatively analysing relevant research using a bibliometric analysis. Methods A long-term, multistage bibliometric analysis was performed. Research articles published in Chinese journals from 1980 to 2019 were retrieved from the Wanfang and China National Knowledge Infrastructure (CNKI) databases. Year of publication, journal name and keywords were extracted by the Bibliographic Items Co-occurrence Matrix Builder (BICOMB). The K/A ratio (the frequency of a keyword among the total number of articles within a certain period) was considered an indicator of the popularity of a keyword in different decades. VOSviewer software was used to construct keyword co-occurrence network maps. Results A total of 16,290 articles were included. The overall number of articles continually increased. However, the number of articles published in the last three years decreased. There were two kinds of keyword frequency trends among the different decades. The K/A ratio of the keyword ‘Plasmodium falciparum’ decreased (17.05 in the 1980s, 13.04% in the 1990s, 9.86 in the 2000s, 5.28 in the 2010s), but those of ‘imported case’ and ‘surveillance’ increased. Drug resistance has been a continuous concern. The keyword co-occurrence network maps showed that the themes of malaria research diversified, and the degree of multidisciplinary cooperation gradually increased. Conclusions This bibliometric analysis revealed the trends in malaria research in China over the past 40 years. The results suggest emphasis on investigation, multidisciplinary participation and drug resistance by researchers and policymakers in malaria epidemic areas. The results also provide domestic experts with qualitative evidence of China’s experience in malaria control and elimination.

High Content and High Throughout Phenotypic Assay for the Hourly Resolution of the Malaria Parasite Erythrocytic Cycle

Over the last 20 years increased funding for malaria research has resulted in very significant technical advances to study the biology of Plasmodium species. High throughput phenotypic assays have been developed to screen millions of compounds and identify small molecules with antiparasitic activity. At the same time, advances in malaria genetic have greatly facilitated the generation of genetically modified parasites, and whole genome genetic screens are now feasible in Plasmodium species. Finally, there has been an increased interest to study malaria parasites at the population level, in particular in the area of drug resistance. Drug resistant field isolates have been collected around the world, and drug resistant strains are routinely generated in the lab to study the mechanisms of drug resistance. As a result, one of the current bottlenecks in malaria research is our ability to quickly characterize the phenotype associated with compound treatment or genetic modification, or to quickly compare differences in intracellular development between strains. Here, we present a high content/high throughput phenotypic assay that combines highly selective RNA, DNA, and RBC membrane dyes to provide hourly resolution of the full erythrocytic cycle for both P. falciparum and P. knowlesi. A flow cytometry assay allows the analysis of samples in a 384-well format and a quick way to determine the parasite developmental stage. On the other hand, the fluorescence microscopy format allows for a detailed visualization of parasite morphology. Finally, using open source software we have developed protocols for the automated cluster analysis of microscopy images. This assay can be applied to any Plasmodium species, requires very little amount of sample, is performed with fixed cells, and is easily scalable. Overall, we believe this assay will be a great tool for the malaria community to study Plasmodium species.