Framing the future for taxonomic monography: Improving recognition, support, and access

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Characterization of Naturally Acquired Immunity to a Panel of Antigens Expressed in Mature P. falciparum Gametocytes.

INTRODUCTION: Naturally acquired immune responses against antigens expressed on the surface of mature gametocytes develop in individuals living in malaria-endemic areas. Evidence suggests that such anti-gametocyte immunity can block the development of the parasite in the mosquito, thus playing a role in interrupting transmission. A better comprehension of naturally acquired immunity to these gametocyte antigens can aid the development of transmission-blocking vaccines and improve our understanding of the human infectious reservoir. METHODS: Antigens expressed on the surface of mature gametocytes that had not previously been widely studied for evidence of naturally acquired immunity were identified for protein expression alongside Pfs230-C using either the mammalian HEK293E or the wheat germ cell-free expression systems. Where there was sequence variation in the candidate antigens (3D7 vs a clinical isolate PfKE04), both variants were expressed. ELISA was used to assess antibody responses against these antigens, as well as against crude stage V gametocyte extract (GE) and AMA1 using archived plasma samples from individuals recruited to participate in malaria cohort studies. We analyzed antibody levels (estimated from optical density units using a standardized ELISA) and seroprevalence (defined as antibody levels greater than three standard deviations above the mean levels of a pool of malaria naïve sera). We described the dynamics of antibody responses to these antigens by identifying factors predictive of antibody levels using linear regression models. RESULTS: Of the 25 antigens selected, seven antigens were produced successfully as recombinant proteins, with one variant antigen, giving a total of eight proteins for evaluation. Antibodies to the candidate antigens were detectable in the study population (N = 216), with seroprevalence ranging from 37.0% (95% CI: 30.6%, 43.9%) for PSOP1 to 77.8% (95% CI: 71.6%, 83.1%) for G377 (3D7 variant). Responses to AMA1 and GE were more prevalent than those to the gametocyte proteins at 87.9% (95% CI: 82.8%, 91.9%) and 88.3% (95% CI: 83.1%, 92.4%), respectively. Additionally, both antibody levels and breadth of antibody responses were associated with age and concurrent parasitaemia. CONCLUSION: Age and concurrent parasitaemia remain important determinants of naturally acquired immunity to gametocyte antigens. Furthermore, we identify novel candidates for transmission-blocking activity evaluation

Framing the future for taxonomic monography: Improving recognition, support, and access

Taxonomic monographs synthesize biodiversity knowledge and document biodiversity change through recent and geological time for a particular organismal group, sometimes also incorporating cultural and place-based knowledge. They are a vehicle through which broader questions about ecological and evolutionary patterns and processes can be generated and answered (e.g., Muñoz Rodríguez et al., 2019). Chiefly, monography represents the foundational research upon which all biological work is based (Hamilton et al., 2021). Moreover, monography can be a pathway to developing inclusive scientific practices, engaging diverse audiences in expanding and disseminating indigenous and local knowledge and significance of place. Apart from the scientific importance of monography, these comprehensive biodiversity treatments are also crucial for policy, conservation, human wellbeing, and the sustainable use of natural resources. Taxonomic, cultural and biodiversity data within monographs aid in the implementation of law and policy, such as the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES), the Nagoya Protocol of the Convention on Biological Diversity (Buck & Hamilton, 2011), and the International Union for Conservation of Nature (IUCN) Red List (e.g., Neo et al., 2017). While vital as a knowledge resource and tool for conservation and research, monographs are not available for many groups of organisms. This is of particular concern for organisms that are threatened with extinction, of medical or economic importance, and those organisms that have the potential to provide insight into biodiversity change over time because they are most susceptible to global change. In discussing the future of collections-based systematics, researchers have highlighted the importance of updated monographic workflows, collaborative teams, and effective ways to educate and disseminate the results of monographs to the public and scientific community (e.g., Wen et al., 2015; Grace et al., 2021). Here, we discuss how improving recognition, support, and access can lead to greater inclusivity while promoting a more active, sustainable, and collaborative outlook for monographic research. </p

Replication Data for: Antibody responses to crude gametocyte extract predicts P. falciparum gametocyte carriage in Kenya

This is a replication dataset for the submitted manuscript titled "Antibody responses to crude gametocyte extract predicts P. falciparum gametocyte carriage in Kenya". The dataset constitutes data from two independent cross sectional studies of participants aged 6 months to 67 years. The AFIRM cohort participants were recruited from Junju in Kilifi County and included 413 individuals recruited from January 2014-February 2015. On the other hand, the KMLC cohort included 287 individuals recruited from Junju and Ngerenya in Kilifi County between 1998-2016. Recorded data for each individual includes participant identifier, age, sex, season (AFIRM Cohort) and transmission setting (KMLC Cohort). The parasite density and antibody concentration are provided

Antibody Responses to Crude Gametocyte Extract Predict Plasmodium falciparum Gametocyte Carriage in Kenya.

BACKGROUND: Malaria caused by Plasmodium falciparum remains a serious global public health challenge especially in Africa. Interventions that aim to reduce malaria transmission by targeting the gametocyte reservoir are key to malaria elimination and/or eradication. However, factors that are associated with gametocyte carriage have not been fully explored. Consequently, identifying predictors of the infectious reservoir is fundamental in the elimination campaign. METHODS: We cultured P. falciparum NF54 gametocytes (to stage V) and prepared crude gametocyte extract. Samples from a total of 687 participants (aged 6 months to 67 years) representing two cross-sectional study cohorts in Kilifi, Kenya were used to assess IgG antibody responses by ELISA. We also analyzed IgG antibody responses to the blood-stage antigen AMA1 as a marker of asexual parasite exposure. Gametocytemia and asexual parasitemia data quantified by microscopy and molecular detection (QT-NASBA) were used to determine the relationship with antibody responses, season, age, and transmission setting. Multivariable logistic regression models were used to study the association between antibody responses and gametocyte carriage. The predictive power of the models was tested using the receiver operating characteristic (ROC) curve. RESULTS: Multivariable logistic regression analysis showed that IgG antibody response to crude gametocyte extract predicted both microscopic (OR=1.81 95% CI: 1.06-3.07, p=0.028) and molecular (OR=1.91, 95% CI: 1.11-3.29, p=0.019) P. falciparum gametocyte carriage. Antibody responses to AMA1 were also associated with both microscopic (OR=1.61 95% CI: 1.08-2.42, p=0.020) and molecular (OR=3.73 95% CI: 2.03-6.74, p<0.001) gametocytemia. ROC analysis showed that molecular (AUC=0.897, 95% CI: 0.868-0.926) and microscopic (AUC=0.812, 95% CI: 0.758-0.865) multivariable models adjusted for gametocyte extract showed very high predictive power. Molecular (AUC=0.917, 95% CI: 0.891-0.943) and microscopic (AUC=0.806, 95% CI: 0.755-0.858) multivariable models adjusted for AMA1 were equally highly predictive. CONCLUSION: In our study, it appears that IgG responses to crude gametocyte extract are not an independent predictor of gametocyte carriage after adjusting for AMA1 responses but may predict gametocyte carriage as a proxy marker of exposure to parasites. Serological responses to AMA1 or to gametocyte extract may facilitate identification of individuals within populations who contribute to malaria transmission and support implementation of transmission-blocking interventions

Replication data for: Characterization of naturally acquired immunity to a panel of antigens expressed in mature P. falciparum gametocytes

We used data from a longitudinally monitored cohort of children and adults from Kilifi county located along the Kenyan coast collected between 1998-2016 to describe the factors associated with the acquisition of antibody responses to antigens expressed on the surface of mature gametocytes. A panel of candidate gametocyte antigens were identified and produced as recombinant protein for this analysis. The datasets comprise data from cross-sectional surveys carried out to assess parasite prevalence. The datasets were used to carry out analyses aimed at describing the seroprevalence of antibodies to the candidate antigens, and assess the factors associated with antibody responses to these antigens. The overall aim of the analyses was to improve our understanding of immunity to the transmissible stages of the malaria parasite