Plasma and cerebrospinal proteomes from childre with cerebral malaria differ from those of children with other encephalopathies

Journal article published in The Journal of Infectious DiseasesClinical signs and symptoms of cerebral malaria in children are nonspecific and are seen in other common encephalopathies in malaria-endemic areas. This makes accurate diagnosis difficult in resource-poor settings. Novel malaria-specific diagnostic and prognostic methods are needed. We have used 2 proteomic strategies to identify differentially expressed proteins in plasma and cerebrospinal fluid from children with a diagnosis of cerebral malaria, compared with those with a diagnosis of malaria-slide-negative acute bacterial meningitis and other nonspecific encephalopathies. Here we report the presence of differentially expressed proteins in cerebral malaria in both plasma and cerebrospinal fluid that could be used to better understand pathogenesis and help develop more-specific diagnostic methods. In particular, we report the expression of 2 spectrin proteins that have known Plasmodium falciparum–binding partners involved in the stability of the infected red blood cell, suppressing further invasion and possibly enhancing the red blood cell’s ability to sequester in microvasculature.Clinical signs and symptoms of cerebral malaria in children are nonspecific and are seen in other common encephalopathies in malaria-endemic areas. This makes accurate diagnosis difficult in resource-poor settings. Novel malaria-specific diagnostic and prognostic methods are needed. We have used 2 proteomic strategies to identify differentially expressed proteins in plasma and cerebrospinal fluid from children with a diagnosis of cerebral malaria, compared with those with a diagnosis of malaria-slide-negative acute bacterial meningitis and other nonspecific encephalopathies. Here we report the presence of differentially expressed proteins in cerebral malaria in both plasma and cerebrospinal fluid that could be used to better understand pathogenesis and help develop more-specific diagnostic methods. In particular, we report the expression of 2 spectrin proteins that have known Plasmodium falciparum–binding partners involved in the stability of the infected red blood cell, suppressing further invasion and possibly enhancing the red blood cell’s ability to sequester in microvasculature

Strengthening capacity for community and public engagement (CPE): a mixed-methods evaluation of the ‘DELTAS Africa CPE seed fund’ pilot

Background: The ‘DELTAS Africa CPE seed fund’ was a pilot scheme designed to strengthen capacity in community and public engagement (CPE) via a ‘learn by doing’ approach. The scheme supported a total of 25 early career researchers and research support staff belonging to the DELTAS Africa network to design and implement a variety of CPE projects between August 2019 and February 2021. We examine recipient experiences of the DELTAS Africa CPE seed fund initiative, changes in their CPE attitudes, knowledge and proficiency and their CPE practice and/or practice intentions post-award. Methods: A mixed-methods process and performance evaluation drawing on three data sources: An anonymous, online knowledge, attitude and practice survey completed by CPE seed fund awardees pre- and post-project implementation (N=23); semi-structured interviews completed with a sub-sample of awardees and programme implementors (N=9); and ‘end-of-project’ reports completed by all seed fund awardees (N=25). Results: All awardees described their seed fund experience in positive terms, despite invariably finding it more challenging than originally anticipated. The combined survey, interview and end of project report data all uniformly revealed improvement in awardees’ self-reported CPE knowledge, attitudes and proficiency by completion of their respective projects. Commitment to continued CPE activity post award was evident in the survey data and all interviewees were adamant that they would integrate CPE within their respective research work going forward. Conclusion: The DELTAS Africa CPE seed fund appeared to work successfully as a CPE capacity strengthening platform and as a vehicle for fostering longer-term interest in CPE activities

Differential Plasmodium falciparum surface antigen expression among children with Malarial Retinopathy

Retinopathy provides a window into the underlying pathology of life-threatening malarial coma (“cerebral malaria”), allowing differentiation between 1) coma caused by sequestration of Plasmodium falciparum-infected erythrocytes in the brain and 2) coma with other underlying causes. Parasite sequestration in the brain is mediated by PfEMP1; a diverse parasite antigen that is inserted into the surface of infected erythrocytes and adheres to various host receptors. PfEMP1 sub-groups called “DC8” and “DC13” have been proposed to cause brain pathology through interactions with endothelial protein C receptor. To test this we profiled PfEMP1 gene expression in parasites from children with clinically defined cerebral malaria, who either had or did not have accompanying retinopathy. We found no evidence for an elevation of DC8 or DC13 PfEMP1 expression in children with retinopathy. However, the proportional expression of a broad subgroup of PfEMP1 called “group A” was elevated in retinopathy patients suggesting that these variants may play a role in the pathology of cerebral malaria. Interventions targeting group A PfEMP1 may be effective at reducing brain pathology

Cognitive testing of a survey instrument to assess sexual practices, behaviours, and health outcomes: a multi-country study protocol

BACKGROUND: Population level data on sexual practices, behaviours and health-related outcomes can ensure that responsive, relevant health services are available for all people of all ages. However, while billions of dollars have been invested in attempting to improve sexual and reproductive health (including HIV) outcomes, far less is understood about associated sexual practices and behaviours. Therefore, the World Health Organization embarked on a global consultative process to develop a short survey instrument to assess sexual health practices, behaviours and health outcomes. In order for the resulting draft survey instrument to be published as a 'global' standard instrument, it is important to first determine that the proposed measures are globally comprehensible and applicable. This paper describes a multi-country study protocol to assess the interpretability and comparability of the survey instrument in a number of diverse countries. METHODS: This study will use cognitive interviewing, a qualitative data collection method that uses semi-structured interviews to explore how participants process and respond to survey instruments. We aim to include study sites in up to 20 countries. The study procedures consist of: (1) localizing the instrument using forward and back-translation; (2) using a series of cognitive interviews to understand how participants engage with each survey question; (3) revising the core instrument based on interview findings; and (4) conducting an optional second round of cognitive interviews. Data generated from interviews will be summarised into a predeveloped analysis matrix. The entire process (a 'wave' of data collection) will be completed simultaneously by 5+ countries, with a total of three waves. This stepwise approach facilitates iterative improvements and sharing across countries. DISCUSSION: An important output from this research will be a revised survey instrument, which when subsequently published, can contribute to improving the comparability across contexts of measures of sexual practices, behaviours and health-related outcomes. Site-specific results of the feasibility of conducting this research may help shift perceptions of who and what can be included in sexual health-related research

Discovery and Validation of Biomarkers to Guide Clinical Management of Pneumonia in African Children

Background Pneumonia is the leading cause of death in children globally. Clinical algorithms remain suboptimal for distinguishing severe pneumonia from other causes of respiratory distress such as malaria or distinguishing bacterial pneumonia and pneumonia from others causes, such as viruses. Molecular tools could improve diagnosis and management. Methods We conducted a mass spectrometry–based proteomic study to identify and validate markers of severity in 390 Gambian children with pneumonia (n = 204) and age-, sex-, and neighborhood-matched controls (n = 186). Independent validation was conducted in 293 Kenyan children with respiratory distress (238 with pneumonia, 41 with Plasmodium falciparum malaria, and 14 with both). Predictive value was estimated by the area under the receiver operating characteristic curve (AUC). Results Lipocalin 2 (Lpc-2) was the best protein biomarker of severe pneumonia (AUC, 0.71 [95% confidence interval, .64–.79]) and highly predictive of bacteremia (78% [64%–92%]), pneumococcal bacteremia (84% [71%–98%]), and “probable bacterial etiology” (91% [84%–98%]). These results were validated in Kenyan children with severe malaria and respiratory distress who also met the World Health Organization definition of pneumonia. The combination of Lpc-2 and haptoglobin distinguished bacterial versus malaria origin of respiratory distress with high sensitivity and specificity in Gambian children (AUC, 99% [95% confidence interval, 99%–100%]) and Kenyan children (82% [74%–91%]). Conclusions Lpc-2 and haptoglobin can help discriminate the etiology of clinically defined pneumonia and could be used to improve clinical management. These biomarkers should be further evaluated in prospective clinical studies

Development of an international sexual and reproductive health survey instrument: results from a pilot WHO/HRP consultative Delphi process

Population health surveys are rarely comprehensive in addressing sexual health, and population-representative surveys often lack standardized measures for collecting comparable data across countries. We present a sexual health survey instrument and implementation considerations for population-level sexual health research. The brief, comprehensive sexual health survey and consensus statement was developed via a multi-step process (an open call, ahackathon, and a modified Delphi process). The survey items, domains, entire instruments, and implementation considerations to develop a sexual health survey were solicited via a global crowdsourcing open call. The open call received 175 contributions from 49 countries. Following review of submissions from the open call, 18 finalists and eight facilitators with expertise in sexual health research, especially in low and middle-income countries (LMICs), were invited to a 3-day hackathon to harmonize a survey instrument. Consensus was achieved through an iterative, modified Delphi process that included three rounds of online surveys. The entire process resulted in a 19-item consensus statement and a brief sexual health survey instrument. This is the first global consensus on a sexual and reproductive health survey instrument that can be used to generate cross-national comparative data in both high-income and LMICs. The inclusive process identified priority domains for improvement and can inform the design of sexual and reproductive health programs and contextually relevant data for comparable research across countries

SARS-CoV-2 seroprevalence in three Kenyan health and demographic surveillance sites, December 2020-May 2021

Background Most of the studies that have informed the public health response to the COVID-19 pandemic in Kenya have relied on samples that are not representative of the general population. We conducted population-based serosurveys at three Health and Demographic Surveillance Systems (HDSSs) to determine the cumulative incidence of infection with SARS-CoV-2. Methods We selected random age-stratified population-based samples at HDSSs in Kisumu, Nairobi and Kilifi, in Kenya. Blood samples were collected from participants between 01 Dec 2020 and 27 May 2021. No participant had received a COVID-19 vaccine. We tested for IgG antibodies to SARS-CoV-2 spike protein using ELISA. Locally-validated assay sensitivity and specificity were 93% (95% CI 88–96%) and 99% (95% CI 98–99.5%), respectively. We adjusted prevalence estimates using classical methods and Bayesian modelling to account for the sampling scheme and assay performance. Results We recruited 2,559 individuals from the three HDSS sites, median age (IQR) 27 (10–78) years and 52% were female. Seroprevalence at all three sites rose steadily during the study period. In Kisumu, Nairobi and Kilifi, seroprevalences (95% CI) at the beginning of the study were 36.0% (28.2–44.4%), 32.4% (23.1–42.4%), and 14.5% (9.1–21%), and respectively; at the end they were 42.0% (34.7–50.0%), 50.2% (39.7–61.1%), and 24.7% (17.5–32.6%), respectively. Seroprevalence was substantially lower among children (&lt;16 years) than among adults at all three sites (p≤0.001). Conclusion By May 2021 in three broadly representative populations of unvaccinated individuals in Kenya, seroprevalence of anti-SARS-CoV-2 IgG was 25–50%. There was wide variation in cumulative incidence by location and age. </jats:sec