Genetic characterization of influenza A(H3N2) viruses circulating in coastal Kenya, 2009-2017

Background Influenza viruses evolve rapidly and undergo immune driven selection, especially in the hemagglutinin (HA) protein. We report amino acid changes affecting antigenic epitopes and receptor‐binding sites of A(H3N2) viruses circulating in Kilifi, Kenya, from 2009 to 2017. Methods Next‐generation sequencing (NGS) was used to generate A(H3N2) virus genomic data from influenza‐positive specimens collected from hospital admissions and health facility outpatients presenting with acute respiratory illness to health facilities within the Kilifi Health and Demographic Surveillance System. Full‐length HA sequences were utilized to characterize A(H3N2) virus genetic and antigenic changes. Results From 186 (90 inpatient and 96 outpatient) influenza A virus‐positive specimens processed, 101 A(H3N2) virus whole genomes were obtained. Among viruses identified in inpatient specimens from 2009 to 2015, divergence of circulating A(H3N2) viruses from the vaccine strains A/Perth/16/2009, A/Texas/50/2012, and A/Switzerland/9715293/2013 formed 6 genetic clades (A/Victoria/208/2009‐like, 3B, 3C, 3C.2a, 4, and 7). Among viruses identified in outpatient specimens from 2015 to 2017, divergence of circulating A(H3N2) viruses from vaccine strain A/Hong Kong/4801/2014 formed clade 3C.2a, subclades 3C.2a2 and 3C.2a3, and subgroup 3C.2a1b. Several amino acid substitutions were associated with the continued genetic evolution of A(H3N2) strains in circulation. Conclusions Our results suggest continuing evolution of currently circulating A(H3N2) viruses in Kilifi, coastal Kenya and suggest the need for continuous genetic and antigenic viral surveillance of circulating seasonal influenza viruses with broad geographic representation to facilitate prompt and efficient selection of influenza strains for inclusion in future influenza vaccines

Developments in Practice XXXII: Successful Strategies for IT Staffing

To explore the current IT staffing challenges and issues, and how organizations are approaching these challenges and issues, we convened a focus group of senior IT managers from a variety of different companies representing several industries. In this study, we explore the number and types of IT skills that senior IT managers perceive important for their organizations, both currently and in the future. We further explore these organizations’ IT staffing practices in hiring, retention, career development and training, and performance, promotion and succession planning. The focus group anticipated some emerging trends in their future IT staffing needs, and shared some interesting techniques and strategies that they used to effectively meet the IT staffing challenges and needs. We describe the efficacy of their current IT staffing practices and the new practices that they introduced to enhance their ability to hire, retain, and develop top candidates

Recent Decisions

Comments on recent decisions by James M. Corcoran, Manuel A. Sequeira, D. D. Robertson, Joseph B. Joyce, A. J. Deutsch, Lawrence J. Dolan, Otto K. Hilbert, and J. Robert Geiman

Quantitative profiling of selective Sox/POU pairing on hundreds of sequences in parallel by Coop-seq

© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. Cooperative binding of transcription factors is known to be important in the regulation of gene expression programs conferring cellular identities. However, current methods to measure cooperativity parameters have been laborious and therefore limited to studying only a few sequence variants at a time. We developed Coop-seq (cooperativity by sequencing) that is capable of efficiently and accurately determining the cooperativity parameters for hundreds of different DNA sequences in a single experiment. We apply Coop-seq to 12 dimer pairs from the Sox and POU families of transcription factors using 324 unique sequences with changed half-site orientation, altered spacing and discrete randomization within the binding elements. The study reveals specific dimerization profiles of different Sox factors with Oct4. By contrast, Oct4 and the three neural class III POU factors Brn2, Brn4 and Oct6 assemble with Sox2 in a surprisingly indistinguishable manner. Two novel half-site configurations can support functional Sox/Oct dimerization in addition to known composite motifs. Moreover, Coop-seq uncovers a nucleotide switch within the POU half-site when spacing is altered, which is mirrored in genomic loci bound by Sox2/Oct4 complexes.Link_to_subscribed_fulltex

A New Source for Electroweak Baryogenesis in the MSSM

One of the most experimentally testable explanations for the origin of the baryon asymmetry of the universe is that it was created during the electroweak phase transition, in the minimal supersymmetric standard model. Previous efforts have focused on the current for the difference of the two Higgsino fields, $H_1-H_2$, as the source of biasing sphalerons to create the baryon asymmetry. We point out that the current for the orthogonal linear combination, $H_1+H_2$, is larger by several orders of magnitude. Although this increases the efficiency of electroweak baryogenesis, we nevertheless find that large CP-violating angles $\ge 0.15$ are required to get a large enough baryon asymmetry.Comment: 4 pages, 2 figures; numerical error corrected, which implies that large CP violation is needed to get observed baryon asymmetry. We improved solution of diffusion equations, and computed more accurate values for diffusion coefficient and damping rate

Epidemiological and evolutionary dynamics of influenza B virus in coastal Kenya as revealed by genomic analysis of strains sampled over a single season

The genomic epidemiology of influenza B virus (IBV) remains understudied in Africa despite significance to design of effective local and global control strategies. We undertook surveillance throughout 2016 in coastal Kenya, recruiting individuals presenting with acute respiratory illness at nine outpatient health facilities (any age) or admitted to the Kilifi County Hospital (<5-year-old). Whole genomes were sequenced for a select 111 positives; 94 (84.7%) of B/Victoria lineage and 17 (15.3%) of B/Yamagata lineage. Inter-Lineage reassortment was detected in 10 viruses; nine with B/Yamagata backbone but B/Victoria NA and NP segments and one with a B/Victoria backbone but B/Yamagata PB2, PB1, PA and MP segments. Five phylogenomic clusters were identified among the sequenced viruses; (i) pure B/Victoria clade 1A (n = 93, 83.8%), (ii) reassortant B/Victoria clade 1A (n = 1, 0.9%), (iii) pure B/Yamagata clade 2 (n = 2, 1.8%), (iv) pure B/Yamagata clade 3 (n = 6, 5.4%) and (v) reassortant B/Yamagata clade 3 (n = 9, 8.1%). Using divergence dates and clustering patterns in the presence of global background sequences, we counted up to 29 independent IBV strain introductions into the study area (∼900 km2) in 2016. Local viruses, including the reassortant B/Yamagata strains, clustered closely with viruses from neighbouring Tanzania and Uganda. Our study demonstrated that genomic analysis provides a clearer picture of locally circulating IBV diversity. The high number of IBV introductions highlights the challenge in controlling local influenza epidemics by targeted approaches e.g. sub-population vaccination or patient quarantine. The finding of divergent IBV strains co-circulating within a single season emphasizes why broad immunity vaccines are the most ideal for influenza control in Kenya

Genomic epidemiology and evolutionary dynamics of respiratory syncytial virus group B in Kilifi, Kenya, 2015-17

Respiratory syncytial virus (RSV) circulates worldwide, occurring seasonally in communities, and is a leading cause of acute respiratory illness in young children. There is paucity of genomic data from purposively sampled populations by which to investigate evolutionary dynamics and transmission patterns of RSV. Here we present an analysis of 295 RSV group B (RSVB) genomes from Kilifi, coastal Kenya, sampled from individuals seeking outpatient care in 9 health facilities across a defined geographical area (∼890 km2), over 2 RSV epidemics between 2015 and 2017. RSVB diversity was characterized by multiple virus introductions into the area and co-circulation of distinct genetic clusters, which transmitted and diversified locally with varying frequency. Increase in relative genetic diversity paralleled seasonal virus incidence. Importantly, we identified a cluster of viruses that emerged in the 2016/17 epidemic, carrying distinct amino-acid signatures including a novel non-synonymous change (K68Q) in antigenic site ∅ in the Fusion protein. RSVB diversity was additionally marked by signature non-synonymous substitutions that were unique to particular genomic clusters, some under diversifying selection. Our findings provide insights into recent evolutionary and epidemiological behaviors of RSV group B, and highlight possible emergence of a novel antigenic variant, which has implications on current prophylactic strategies in development

Implications of gestational age at antenatal care attendance on the successful implementation of a maternal respiratory syncytial virus (RSV) vaccine program in coastal Kenya

Background: Maternal immunisation to boost respiratory syncytial virus (RSV) specific antibodies in pregnant women is a strategy to enhance infant protection. The timing of maternal vaccination during pregnancy may be critical for its effectiveness. However, Kenya has no documented published data on gestational age distribution of pregnant women attending antenatal care (ANC), or the proportion of women attending ANC during the proposed window period for vaccination, to inform appropriate timing for delivery or estimate potential uptake of this vaccine. Methods: A cross-sectional survey was conducted within the Kilifi Health and Demographic Surveillance System (KHDSS), coastal Kenya. A simple random sample of 1000 women who had registered pregnant in 2017 to 2018 and with a birth outcome by the time of data collection was taken. The selected women were followed at their homes, and individually written informed consent was obtained. Records of their antenatal attendance during pregnancy were abstracted from their ANC booklet. The proportion of all pregnant women from KHDSS (55%) who attended for one or more ANC in 2018 was used to estimate vaccine coverage. Results: Of the 1000 women selected, 935 were traced with 607/935 (64.9%) available for interview, among whom 470/607 (77.4%) had antenatal care booklets. The median maternal age during pregnancy was 28.6 years. The median (interquartile range) gestational age in weeks at the first to fifth ANC attendance was 26 (21–28), 29 (26–32), 32 (28–34), 34 (32–36) and 36 (34–38), respectively. The proportion of women attending for ANC during a gestational age window for vaccination of 28–32 weeks (recommended), 26–33 weeks and 24–36 weeks was 76.6% (360/470), 84.5% (397/470) and 96.2% (452/470), respectively. Estimated vaccine coverage was 42.1, 46.5 and 52.9% within the narrow, wide and wider gestational age windows, respectively. Conclusions: In a random sample of pregnant women from Kilifi HDSS, Coastal Kenya with card-confirmed ANC clinic attendance, 76.6% would be reached for maternal RSV vaccination within the gestational age window of 28–32 weeks. Widening the vaccination window (26–33 weeks) or (24–36 weeks) would not dramatically increase vaccine coverage and would require consideration of antibody kinetics data that could affect vaccine efficacy

Quantifying maternally derived respiratory syncytial virus specific neutralising antibodies in a birth cohort from coastal Kenya.

BACKGROUND: Severe respiratory syncytial virus (RSV) disease occurs predominantly in children under 6 months of age. There is no licensed RSV vaccine. Protection of young infants could be achieved by a maternal vaccine to boost titres of passively transferred protective antibodies. Data on the level and kinetics of functional RSV-specific antibody at birth and over the early infant period would inform vaccine product design. METHODS: From a birth cohort study (2002-2007) in Kilifi, Kenya, 100 participants were randomly selected for whom cord blood and 2 subsequent 3-monthly blood samples within the first year of life, were available. RSV antibodies against the A2 strain of RSV were assayed and recorded as the logarithm (base 2) plaque reduction neutralisation test (PRNT) titre. Analysis by linear regression accounted for within-person clustering. RESULTS: The geometric mean neutralisation antibody titre was 10.6 (SD: 1.13) at birth with a log-linear decay over the first 6 months of life. The estimated rate of decay was -0.58 (SD: 0.20) log2PRNT titre per month and a half-life of 36 days. There was no significant interaction between cord titre and rate of decay with age. Mean cord titres rose and fell in a pattern temporally tracking community virus transmission. CONCLUSIONS: In this study population, RSV neutralising antibody titres decay approximately two-fold every one month. The rate of decay varies widely by individual but is not related to titre at birth. RSV specific cord titres vary seasonally, presumably due to maternal boosting

Surveillance of respiratory viruses among children attending a primary school in rural coastal Kenya

Background: Respiratory viruses are primary agents of respiratory tract diseases. Knowledge on the types and frequency of respiratory viruses affecting school-children is important in determining the role of schools in transmission in the community and identifying targets for interventions. Methods: We conducted a one-year (term-time) surveillance of respiratory viruses in a rural primary school in Kilifi County, coastal Kenya between May 2017 and April 2018. A sample of 60 students with symptoms of ARI were targeted for nasopharyngeal swab (NPS) collection weekly. Swabs were screened for 15 respiratory virus targets using real time PCR diagnostics. Data from respiratory virus surveillance at the local primary healthcare facility was used for comparison. Results: Overall, 469 students aged 2-19 years were followed up for 220 days. A total of 1726 samples were collected from 325 symptomatic students; median age of 7 years (IQR 5-11). At least one virus target was detected in 384 (22%) of the samples with a frequency of 288 (16.7%) for rhinovirus, 47 (2.7%) parainfluenza virus, 35 (2.0%) coronavirus, 15 (0.9%) adenovirus, 11 (0.6%) respiratory syncytial virus (RSV) and 5 (0.3%) influenza virus. The proportion of virus positive samples was higher among lower grades compared to upper grades (25.9% vs 17.5% respectively; χ2 = 17.2, P -value <0.001). Individual virus target frequencies did not differ by age, sex, grade, school term or class size. Rhinovirus was predominant in both the school and outpatient setting. Conclusion: Multiple respiratory viruses circulated in this rural school population. Rhinovirus was dominant in both the school and outpatient setting and RSV was of notably low frequency in the school. The role of school children in transmitting viruses to the household setting is still unclear and further studies linking molecular data to contact patterns between the school children and their households are required