Adaptive divergence in shell morphology in an ongoing gastropod radiation from Lake Malawi

Background Ecological speciation is a prominent mechanism of diversification but in many evolutionary radiations, particularly in invertebrates, it remains unclear whether supposedly critical ecological traits drove or facilitated diversification. As a result, we lack accurate knowledge on the drivers of diversification for most evolutionary radiations along the tree of life. Freshwater mollusks present an enigmatic example: Putatively adaptive radiations are being described in various families, typically from long-lived lakes, whereas other taxa represent celebrated model systems in the study of ecophenotypic plasticity. Here we examine determinants of shell-shape variation in three nominal species of an ongoing ampullariid radiation in the Malawi Basin (Lanistes nyassanus, L. solidus and Lanistes sp. (ovum-like)) with a common garden experiment and semi-landmark morphometrics. Results We found significant differences in survival and fecundity among these species in contrasting habitats. Morphological differences observed in the wild persisted in our experiments for L. nyassanus versus L. solidus and L. sp. (ovum-like), but differences between L. solidus and L. sp. (ovum-like) disappeared and re-emerged in the F-1 and F-2 generations, respectively. These results indicate that plasticity occurred, but that it is not solely responsible for the observed differences. Our experiments provide the first unambiguous evidence for genetic divergence in shell morphology in an ongoing freshwater gastropod radiation in association with marked fitness differences among species under controlled habitat conditions. Conclusions Our results indicate that differences in shell morphology among Lanistes species occupying different habitats have an adaptive value. These results also facilitate an accurate reinterpretation of morphological variation in fossil Lanistes radiations, and thus macroevolutionary dynamics. Finally, our work testifies that the shells of freshwater gastropods may retain signatures of adaptation at low taxonomic levels, beyond representing an evolutionary novelty responsible for much of the diversity and disparity in mollusks altogether

Avidity of anti-circumsporozoite antibodies following vaccination with RTS,S/AS01(E) in young children

Background: The nature of protective immune responses elicited by immunization with the candidate malaria vaccine RTS, S is still incompletely understood. Antibody levels correlate with protection against malaria infection, but considerable variation in outcome is unexplained (e.g., children may experience malaria despite high anticircumsporozoite [CS] titers). Methods and Findings: We measured the avidity index (AI) of the anti-CS antibodies raised in subgroup of 5-17 month old children in Kenya who were vaccinated with three doses of RTS, S/AS01(E) between March and August 2007. We evaluated the association between the AI and the subsequent risk of clinical malaria. We selected 19 cases (i.e., with clinical malaria) and 42 controls (i.e., without clinical malaria), matching for anti-CS antibody levels and malaria exposure. We assessed their sera collected 1 month after the third dose of the vaccine, in March 2008 (range 4-10 months after the third vaccine), and at 12 months after the third vaccine dose. The mean AI was 45.2 (95% CI: 42.4 to 48.1), 45.3 (95% CI: 41.4 to 49.1) and 46.2 (95% CI; 43.2 to 49.3) at 1 month, in March 2008 (4-10 months), and at 12 months after the third vaccination, respectively (p=0.9 by ANOVA test for variation over time). The AI was not associated with protection from clinical malaria (OR=0.90; 95% CI: 0.49 to 1.66; p=0.74). The AI was higher in children with high malaria exposure, as measured using the weighted local prevalence of malaria, compared to those with low malaria exposure at 1 month post dose 3 (p=0.035). Conclusion: Our data suggest that in RTS, S/AS01(E)-vaccinated children residing in malaria endemic countries, the avidity of anti-circumsporozoite antibodies, as measured using an elution ELISA method, was not associated with protection from clinical malaria. Prior natural malaria exposure might have primed the response to RTS, S/AS01(E) vaccination

Low Mannose-Binding Lectin Concentration Is Associated with Severe Infection in Patients with Hematological Cancer Who Are Undergoing Chemotherapy

Background. Mannose-binding lectin (MBL) is a serum lectin involved in innate immune response. Low serum MBL concentration may constitute a risk factor for infection in patients receiving myelosuppressive chemotherapy. Methods. We conducted a prospective, observational study that assessed MBL concentration as a risk factor for infection in patients with hematological malignancy who were hospitalized to undergo at least 1 chemotherapy cycle. MBL deficiency was defined using an algorithm that considered the serum MBL concentration and the MBL genotype. The primary end point was the ratio of duration of febrile neutropenia to the duration of neutropenia. Secondary end points included the incidence of severe infection (e.g., sepsis, pneumonia, bacteremia, and invasive fungal infection). Logistic regression analysis was conducted, and Fisher's exact test was used to analyze binary outcomes, and Kaplan-Meier estimates and log rank tests were used for time-to-event variables. Results. We analyzed 255 patients who received 569 cycles of chemotherapy. The median duration of neutropenia per cycle was 7 days (interquartile range, 0-13 days). Sixty-two patients (24%) were found to have MBL deficiency. Febrile neutropenia occurred at least once in 200 patients. No difference in the primary outcome was seen. The incidence of severe infection was higher among MBL-deficient patients than among non-MBL-deficient patients (1.96 vs. 1.34 cases per 100 days for analysis of all patients [P = .008] and 1.85 vs. 0.94 cases per 100 days excluding patients with acute leukemia [P < .001]). Conclusions. MBL deficiency does not predispose adults with hematological cancer to more-frequent or more-prolonged febrile episodes during myelosuppressive chemotherapy, but MBL-deficient patients have a greater number of severe infections and experience their first severe infection earlier, compared with nondeficient patient

Maternal immunization against Group B streptococcus: World Health Organization research and development technological roadmap and preferred product characteristics.

Group B streptococcus, found in the vagina or lower gastrointestinal tract of about 10-40% of women of reproductive age, is a leading cause of early life invasive bacterial disease, potentially amenable to prevention through maternal immunization during pregnancy. Following a consultation process with global stakeholders, the World Health Organization is herein proposing priority research and development pathways and preferred product characteristics for GBS vaccines, with the aim to facilitate and accelerate vaccine licensure, policy recommendation for wide scale use and implementation

Commentaire

Therapeutic resistance remains the principal problem in acute myeloid leukemia (AML). We used area under receiver-operating characteristic curves (AUCs) to quantify our ability to predict therapeutic resistance in individual patients, where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using data from 4601 patients with newly diagnosed AML given induction therapy with 3+7 or more intense standard regimens in UK Medical Research Council/National Cancer Research Institute, Dutch–Belgian Cooperative Trial Group for Hematology/Oncology/Swiss Group for Clinical Cancer Research, US cooperative group SWOG and MD Anderson Cancer Center studies. Age, performance status, white blood cell count, secondary disease, cytogenetic risk and FLT3-ITD/NPM1 mutation status were each independently associated with failure to achieve complete remission despite no early death (‘primary refractoriness’). However, the AUC of a bootstrap-corrected multivariable model predicting this outcome was only 0.78, indicating only fair predictive ability. Removal of FLT3-ITD and NPM1 information only slightly decreased the AUC (0.76). Prediction of resistance, defined as primary refractoriness or short relapse-free survival, was even more difficult. Our limited ability to forecast resistance based on routinely available pretreatment covariates provides a rationale for continued randomization between standard and new therapies and supports further examination of genetic and posttreatment data to optimize resistance prediction in AML

Natural variation in immune responses to neonatal mycobacterium bovis bacillus calmette-guerin (BCG) vaccination in a cohort of Gambian infants

Background There is a need for new vaccines for tuberculosis (TB) that protect against adult pulmonary disease in regions where BCG is not effective. However, BCG could remain integral to TB control programmes because neonatal BCG protects against disseminated forms of childhood TB and many new vaccines rely on BCG to prime immunity or are recombinant strains of BCG. Interferon-gamma (IFN-) is required for immunity to mycobacteria and used as a marker of immunity when new vaccines are tested. Although BCG is widely given to neonates IFN- responses to BCG in this age group are poorly described. Characterisation of IFN- responses to BCG is required for interpretation of vaccine immunogenicity study data where BCG is part of the vaccination strategy. Methodology/Principal Findings 236 healthy Gambian babies were vaccinated with M. bovis BCG at birth. IFN-, interleukin (IL)-5 and IL-13 responses to purified protein derivative (PPD), killed Mycobacterium tuberculosis (KMTB), M. tuberculosis short term culture filtrate (STCF) and M. bovis BCG antigen 85 complex (Ag85) were measured in a whole blood assay two months after vaccination. Cytokine responses varied up to 10 log-fold within this population. The majority of infants (89-98% depending on the antigen) made IFN- responses and there was significant correlation between IFN- responses to the different mycobacterial antigens (Spearman’s coefficient ranged from 0.340 to 0.675, p=10-6-10-22). IL-13 and IL-5 responses were generally low and there were more non-responders (33-75%) for these cytokines. Nonetheless, significant correlations were observed for IL-13 and IL-5 responses to different mycobacterial antigens Conclusions/Significance Cytokine responses to mycobacterial antigens in BCG-vaccinated infants are heterogeneous and there is significant inter-individual variation. Further studies in large populations of infants are required to identify the factors that determine variation in IFN- responses

Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children: Why, What, and How to Undertake Estimates?

Improving maternal, newborn, and child health is central to Sustainable Development Goal targets for 2030, requiring acceleration especially to prevent 5.6 million deaths around the time of birth. Infections contribute to this burden, but etiological data are limited. Group B Streptococcus (GBS) is an important perinatal pathogen, although previously focus has been primarily on liveborn children, especially early-onset disease. In this first of an 11-article supplement, we discuss the following: (1) Why estimate the worldwide burden of GBS disease? (2) What outcomes of GBS in pregnancy should be included? (3) What data and epidemiological parameters are required? (4) What methods and models can be used to transparently estimate this burden of GBS? (5) What are the challenges with available data? and (6) How can estimates address data gaps to better inform GBS interventions including maternal immunization? We review all available GBS data worldwide, including maternal GBS colonization, risk of neonatal disease (with/without intrapartum antibiotic prophylaxis), maternal GBS disease, neonatal/infant GBS disease, and subsequent impairment, plus GBS-associated stillbirth, preterm birth, and neonatal encephalopathy. We summarize our methods for searches, meta-analyses, and modeling including a compartmental model. Our approach is consistent with the World Health Organization (WHO) Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER), published in The Lancet and the Public Library of Science (PLoS). We aim to address priority epidemiological gaps highlighted by WHO to inform potential maternal vaccination