Evaluating Health Workers' Potential Resistance to New Interventions: A Role for Discrete Choice Experiments

BACKGROUND: The currently recommended approach for preventing malaria in pregnancy (MiP), intermittent preventive treatment with sulphadoxine-pyrimethamine (SP-IPT), has been questioned due to the spread of resistance to SP. Whilst trials are underway to test the efficacy of future alternative approaches, it is important to start exploring the feasibility of their implementation. METHODS AND FINDINGS: This study uses a discrete choice experiment (DCE) method to assess the potential resistance of health workers to changing strategies for control of MiP. In Ashanti region in Ghana, 133 antenatal clinic health workers were presented with 16 choice sets of two alternative policy options, each consisting of a bundle of six attributes representing certain clinical guidelines for controlling MiP (type of approach and drug used), possible associated maternal and neo-natal outcomes, workload and financial incentives. The data were analysed using a random effects logit model. Overall, staff showed a preference for a curative approach with pregnant women tested for malaria parasites and treated only if positive, compared to a preventive approach (OR 1.6; p = 0.001). Increasing the incidence of low birth weight or severe anaemia by 1% would reduce the odds of preferring an approach by 18% and 10% respectively. Midwives were more resistant to potential changes to current guidelines than lower-level cadres. CONCLUSIONS: In Ashanti Region, resistance to change by antenatal clinic workers from a policy of SP-IPT to IST would generally be low, and it would disappear amongst midwives if health outcomes for the mother and baby were improved by the new strategy. DCEs are a promising approach to identifying factors that will increase the likelihood of effective implementation of new interventions immediately after their efficacy has been proven

Asthma inflammatory phenotypes on four continents: most asthma is non-eosinophilic.

BACKGROUND: Most studies assessing pathophysiological heterogeneity in asthma have been conducted in high-income countries (HICs), with little known about the prevalence and characteristics of different asthma inflammatory phenotypes in low-and middle-income countries (LMICs). This study assessed sputum inflammatory phenotypes in five centres, in Brazil, Ecuador, Uganda, New Zealand (NZ) and the United Kingdom (UK). METHODS: We conducted a cross-sectional study of 998 asthmatics and 356 non-asthmatics in 2016-20. All centres studied children and adolescents (age range 8-20 years), except the UK centre which involved 26-27 year-olds. Information was collected using questionnaires, clinical characterization, blood and induced sputum. RESULTS: Of 623 asthmatics with sputum results, 39% (243) were classified as eosinophilic or mixed granulocytic, i.e. eosinophilic asthma (EA). Adjusted for age and sex, with NZ as baseline, the UK showed similar odds of EA (odds ratio 1.04, 95% confidence interval 0.37-2.94) with lower odds in the LMICs: Brazil (0.73, 0.42-1.27), Ecuador (0.40, 0.24-0.66) and Uganda (0.62, 0.37-1.04). Despite the low prevalence of neutrophilic asthma in most centres, sputum neutrophilia was increased in asthmatics and non-asthmatics in Uganda. CONCLUSIONS: This is the first time that sputum induction has been used to compare asthma inflammatory phenotypes in HICs and LMICs. Most cases were non-eosinophilic, including in settings where corticosteroid use was low. A lower prevalence of EA was observed in the LMICs than in the HICs. This has major implications for asthma prevention and management, and suggests that novel prevention strategies and therapies specifically targeting non-eosinophilic asthma are required globally

Placental Plasmodium falciparum malaria infection: Operational accuracy of HRP2 rapid diagnostic tests in a malaria endemic setting

<p>Abstract</p> <p>Background</p> <p>Malaria has a negative effect on the outcome of pregnancy. Pregnant women are at high risk of severe malaria and severe haemolytic anaemia, which contribute 60-70% of foetal and perinatal losses. Peripheral blood smear microscopy under-estimates sequestered placental infections, therefore malaria rapid diagnostic tests (RDTs) detecting histidine rich protein-2 antigen (HRP-2) in peripheral blood are a potential alternative.</p> <p>Methods</p> <p>HRP-2 RDTs accuracy in detecting malaria in pregnancy (MIP >28 weeks gestation) and placental <it>Plasmodium falciparum </it>malaria (after childbirth) were conducted using Giemsa microscopy and placental histopathology respectively as the reference standard. The study was conducted in Mbale Hospital, using the midwives to perform and interpret the RDT results. Discordant results samples were spot checked using PCR techniques.</p> <p>Results</p> <p>Among 433 febrile women tested, RDTs had a sensitivity of 96.8% (95% CI 92-98.8), specificity of 73.5% (95% CI 67.8-78.6), a positive predictive value (PPV) of 68.0% (95% CI 61.4-73.9), and negative predictive value (NPV) of 97.5% (95% CI 94.0-99.0) in detecting peripheral <it>P. falciparum </it>malaria during pregnancy. At delivery, in non-symptomatic women, RDTs had a 80.9% sensitivity (95% CI 57.4-93.7) and a 87.5% specificity (95%CI 80.9-92.1), PPV of 47.2% (95% CI 30.7-64.2) and NPV of 97.1% (95% CI 92.2-99.1) in detecting placental <it>P. falciparum </it>infections among 173 samples. At delivery, 41% of peripheral infections were detected by microscopy without concurrent placental infection. The combination of RDTs and microscopy improved the sensitivity to 90.5% and the specificity to 98.4% for detecting placental malaria infection (McNemar's <it>X </it>²> 3.84). RDTs were not superior to microscopy in detecting placental infection (McNemar's <it>X </it>²< 3.84). Presence of malaria in pregnancy and active placental malaria infection were 38% and 12% respectively. Placental infections were associated with poor pregnancy outcome [pre-term, still birth and low birth weight] (aOR = 37.9) and late pregnancy malaria infection (aOR = 20.9). Mosquito net use (aOR 2.1) and increasing parity (aOR 2.7) were associated with lower risk for malaria in pregnancy.</p> <p>Conclusion</p> <p>Use of HRP-2 RDTs to detect malaria in pregnancy in symptomatic women was accurate when performed by midwives. A combination of RDTs and microscopy provided the best means of detecting placental malaria. RDTs were not superior to microscopy in detecting placental infection. With a high sensitivity and specificity, RDTs could be a useful tool for assessing malaria in pregnancy, with further (cost-) effectiveness studies.</p

Image analysis in light sheet fluorescence microscopy images of transgenic zebrafish vascular development

The zebrafish has become an established model to study vascular development and disease in vivo. However, despite it now being possible to acquire high-resolution data with state-of-the-art fluorescence microscopy, such as lightsheet microscopy, most data interpretation in pre-clinical neurovascular research relies on visual subjective judgement, rather than objective quantification. Therefore, we describe the development of an image analysis workflow towards the quantification and description of zebrafish neurovascular development. In this paper we focus on data acquisition by lightsheet fluorescence microscopy, data properties, image pre-processing, and vasculature segmentation, and propose future work to derive quantifications of zebrafish neurovasculature development

The Malaria in Pregnancy Library: a bibliometric review

BACKGROUND: The Malaria in Pregnancy (MiP) Library is a bibliographic database that was created by the MiP Consortium in 2005 and is updated every four months using a standardized search protocol. A bibliometric review was conducted of the contents of the Library to determine dynamics in the type, content and volume of literature on malaria in pregnancy over time. METHODS: Data on year of publication, type, language, country of first-author affiliation and content (topic) were extracted from entries in the MiP Library and plotted over time. RESULTS: By January 2012, the MiP Library contained 5,346 entries, consisting of 3,721 journal articles (69.6%), 697 reports (13.0%), 219 academic theses (4.1%), 92 books or book chapters (1.7%), 487 conference proceedings (9.1%), 68 registered studies (1.3%) and 62 'other' (1.2%). Most of the sources were in English language (87.3%), followed by French (7.5%) and Spanish (1.5%). Over 40% of source material was publicly available online (42.4%) and the remaining with restricted access (35.0%) or otherwise unavailable (22.7%). The number of journal articles related to malaria in pregnancy increased from 41 in the 1960s, to 708 in the 1990s, and 1,895 between 2000 and 2009, and the variety of themes has increased over time. English-language articles were sourced from 737 different journals. The top three journals were the American Journal of Tropical Medicine and Hygiene (184), Malaria Journal (158) and the Transactions of the Royal Society of Tropical Medicine and Hygiene (131). CONCLUSION: The last decade has seen a dramatic increase in publications related to malaria in pregnancy, and an increasing proportion of these are publically available online. The MiP Library is a useful, scholarly source for literature and systematic reviews related to malaria in pregnancy