Filters








94 Hits in 1.0 sec

HLA*PRG:LA – HLA typing from linearly projected graph alignments [article]

Alexander T Dilthey, Alexander J Mentzer, Raphael Carapito, Clare Cutland, Nezih Cereb, Shabir A. Madhi, Arang Rhie, Sergey Koren, Seiamak Bahram, Gil McVean, Adam M Phillippy
2018 bioRxiv   pre-print
AbstractSummary:HLA*PRG:LA implements a new graph alignment model for HLA type inference, based on the projection of linear alignments onto a variation graph. It enables accurate HLA type inference from whole-genome (99% accuracy) and whole-exome (93% accuracy) Illumina data; from long-read Oxford Nanopore and Pacific Biosciences data (98% accuracy for whole-genome and targeted data); and from genome assemblies. Computational requirements for a typical sample vary between 0.7 and 14 CPU hours
more » ... r sample.Availability and Implementation:HLA*PRG:LA is implemented in C++ and Perl and freely available from https://github.com/DiltheyLab/HLA-PRG-LA (GPL v3).Contact:alexander.dilthey@med.uni-duesseldorf.deSupplementary informationSupplementary data are available online.
doi:10.1101/453555 fatcat:juirt2e2qzgrhidqmeyonc6ty4

HLA*LA – HLA typing from linearly projected graph alignments

Alexander T Dilthey, Alexander J Mentzer, Raphael Carapito, Clare Cutland, Nezih Cereb, Shabir A Madhi, Arang Rhie, Sergey Koren, Seiamak Bahram, Gil McVean, Adam M Phillippy, Bonnie Berger
2019 Bioinformatics  
HLA*LA implements a new graph alignment model for human leukocyte antigen (HLA) type inference, based on the projection of linear alignments onto a variation graph. It enables accurate HLA type inference from whole-genome (99% accuracy) and whole-exome (93% accuracy) Illumina data; from long-read Oxford Nanopore and Pacific Biosciences data (98% accuracy for whole-genome and targeted data) and from genome assemblies. Computational requirements for a typical sample vary between 0.7 and 14 CPU
more » ... rs per sample. HLA*LA is implemented in C++ and Perl and freely available as a bioconda package or from https://github.com/DiltheyLab/HLA-LA (GPL v3). Supplementary data are available at Bioinformatics online.
doi:10.1093/bioinformatics/btz235 pmid:30942877 pmcid:PMC6821427 fatcat:kw4v46i6mffc3hgdzqlskkrg2a

Temporal Changes in Invasive Group B Streptococcus Serotypes: Implications for Vaccine Development

Ziyaad Dangor, Clare L. Cutland, Alane Izu, Gaurav Kwatra, Siobhan Trenor, Sanjay G. Lala, Shabir A. Madhi, Adam J. Ratner
2016 PLoS ONE  
Methods From 2005 to 2014, infants less than 90 days of age with invasive GBS disease were identified through sentinel laboratory and hospital admission surveillance at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa. Results We identified 820 cases of invasive GBS disease, including 55% among newborns <7 days age (i.e. early-onset disease; EOD). The overall incidence (per 1,000 live births) of invasive GBS disease was 2.59 (95% CI: 2.42-2.77), including 1.41 (95% CI:
more » ... for EOD and 1.18 (95% CI: 1.06-1.30) in infants 7-89 days age (late-onset disease). Year-on-year, from 2005 to 2014, we observed a 9.4% increase in incidence of serotype Ia invasive disease (RR: 1.09; 95% CI: 1.04-1.15; p<0.001), and a 7.4% decline in serotype III invasive disease (RR: 0.93; 95% CI: 0.90-0.96; p<0.001). Overall, serotypes Ia (28.2%), III (55.4%) and V (7.9%) were the commonest disease causing serotypes. Conclusions The incidence of invasive GBS disease has remained persistently high in our setting, with some changes in serotype distribution, albeit mainly involving the same group of dominant serotypes.
doi:10.1371/journal.pone.0169101 pmid:28036363 pmcid:PMC5201280 fatcat:bejs7rfxnjep5h5oe764vdjxa4

Association between antibodies against group B Streptococcus surface proteins and recto-vaginal colonisation during pregnancy

Sonwabile Dzanibe, Gaurav Kwatra, Peter V. Adrian, Sheila Z. Kimaro-Mlacha, Clare L. Cutland, Shabir A. Madhi
2017 Scientific Reports  
Group B Streptococcus (GBS) recto-vaginal colonisation in pregnant women is the major risk factor for early-onset invasive GBS disease in their newborns. We aimed to determine the association between serum antibody levels against 11 GBS surface proteins and recto-vaginal acquisition of GBS colonisation during pregnancy. Sera collected from pregnant women at 20-25 weeks and ≥37 weeks of gestation age were measured for IgG titres against GBS surface proteins using a multiplex immunoassay. Women
more » ... re evaluated for recto-vaginal colonisation every 4-5 weeks. We observed that the likelihood of becoming colonised with GBS during pregnancy was lower in women with IgG titres ≥200 U/mL against gbs0233 (adjusted OR = 0.47 [95% CI: 0.25-0.89], p = 0.021) and ≥85 U/mL for gbs1539 (adjusted OR = 0.44 [95% CI: 0.24-0.82], p = 0.01) when comparing between women who acquired GBS colonisation and those that remained free of GBS colonisation throughout pregnancy. IgG titres (U/mL) specific to BibA and Sip were higher in pregnant women colonised with GBS (380.19 and 223.87, respectively) compared to women with negative GBS cultures (234.42 and 186.21, respectively; p < 0.01) at ≥37 weeks gestation. Antibodies induced by gbs0233 and gbs1539 were associated with a reduced likelihood of recto-vaginal GBS acquisition during pregnancy and warrant further investigation as vaccine targets. Group B Streptococcus (GBS) is a leading cause of invasive bacterial disease in the first seven days of life (i.e. early-onset diseases; EOD) 1 , with 90% of the cases occurring within the first 24 hours of life 2,3 . Recto-vaginal GBS colonisation during pregnancy is the strongest independent risk factor associated with EOD, in which colonised pregnant women vertically transmit GBS to their newborns either in utero or intrapartum. About 10-30% of women are colonised with GBS in the gastrointestinal and genitourinary tract, with colonisation occurring in an intermittent, transient and persistent manner during pregnancy 4-6 . GBS colonisation in the genitourinary tract of women also causes clinical and subclinical acute infections, including chorioamnionitis, endometritis and urinary tract infections 7 . Moreover, GBS colonisation during pregnancy is associated with, late miscarriages, premature birth and stillbirths 8 . Intrapartum antibiotic prophylaxis (IAP) treatment of women colonised with GBS at 35-37 weeks of gestation age is the recommended strategy to reduce vertical transmission. Since the adoption of IAP treatment in high-income settings, the number of reported EOD cases has declined by 80% 9,10 , however, such a strategy remains logistically challenging and unlikely to be cost-effective for low-income countries, including in settings where 40-60% of deliveries occur outside of health-care settings 11, 12 . Alternative strategies to prevent EOD and other GBS related pregnancy complications are being studied, such as maternal immunisation during pregnancy using GBS capsular polysaccharides (CPS) conjugated to carrier
doi:10.1038/s41598-017-16757-9 pmid:29184151 pmcid:PMC5705700 fatcat:qnjoovhtyvh43bb5gbqtyqwyuq

Invasive Group B Streptococcal Disease in South Africa: Importance of Surveillance Methodology

Vanessa Quan, Jennifer R. Verani, Cheryl Cohen, Anne von Gottberg, Susan Meiring, Clare L. Cutland, Stephanie J. Schrag, Shabir A. Madhi, Jose Melo-Cristino
2016 PLoS ONE  
were drawn down from the electronic database at CHBAH laboratory and these cases were cross-matched with the cases identified through the systematic surveillance platform (personal communication CL Cutland  ... 
doi:10.1371/journal.pone.0152524 pmid:27055184 pmcid:PMC4824385 fatcat:ucp7kgaiabgbzo66sjoj7t3acy

Serotype-Specific Acquisition and Loss of Group B Streptococcus Recto-Vaginal Colonization in Late Pregnancy

Gaurav Kwatra, Peter V. Adrian, Tinevimbo Shiri, Eckhart J. Buchmann, Clare L. Cutland, Shabir A. Madhi, Bernard Beall
2014 PLoS ONE  
Maternal recto-vaginal colonization with Group B Streptococcus (GBS) and consequent vertical transmission to the newborn predisposes neonates to early-onset invasive GBS disease. This study aimed to determine the acquisition and loss of serotype-specific recto-vaginal GBS colonization from 20-37+ weeks of gestational age. Methods: Vaginal and rectal swabs were collected from HIV-uninfected women at 20-25 weeks of gestation age and at 5-6 weekly intervals thereafter. Swabs were cultured for GBS
more » ... nd isolates were serotyped by latex agglutination. Serologically non-typable isolates and pilus islands were characterized by PCR. Results: The prevalence of recto-vaginal GBS colonization was 33.0%, 32.7%, 28.7% and 28.4% at 20-25 weeks, 26-30 weeks, 31-35 weeks and 37+ weeks of gestational age, respectively. The most common identified serotypes were Ia (39.2%), III (32.8%) and V (12.4%). Of 507 participants who completed all four study visits, the cumulative overall recto-vaginal acquisition rate of new serotypes during the study was 27.9%, including 11.2%, 8.2% and 4.3% for serotypes Ia, III and V, respectively. Comparing the common colonizing serotypes, serotype III was more likely to be associated with persistent colonization throughout the study (29%) than Ia (18%; p = 0.045) or V (6%; p = 0.002). The median duration of recto-vaginal GBS colonization for serotype III was 6.35 weeks, which was longer than other serotypes. Pilus island proteins were detected in all GBS isolates and their subtype distribution was associated with specific serotypes. Conclusion: South African pregnant women have a high prevalence of GBS recto-vaginal colonization from 20 weeks of gestational age onwards, including high GBS acquisition rates in the last pregnancy-trimesters. There are differences in specific-serotype colonization patterns during pregnancy.
doi:10.1371/journal.pone.0098778 pmid:24979575 pmcid:PMC4076185 fatcat:dywotlxwx5gdxlbc5izibagcfa

Immunization in pregnancy safety surveillance in low and middle-income countries- field performance and validation of novel case definitions

Sonali Kochhar, Ed Clarke, Alane Izu, Kebonethebe Emmanuel Kekane – Mochwari, Clare L. Cutland
2019 Vaccine  
A globally standardized approach in high and low and middle-income countries (LMIC) to actively monitor the safety of vaccines for pregnant women during development and implementation phases is critical. Brighton Collaboration's (BC) Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project has developed globally standardized case definitions (CDs) of key obstetric and neonatal terms for the assessment of safety of vaccines in pregnancy. CDs are categorized into levels of
more » ... agnostic certainty, facilitating their use in varied settings. This study evaluates the field performance of CDs in LMIC.
doi:10.1016/j.vaccine.2019.03.074 pmid:31014963 fatcat:jhpt7o64qjghjn7ghsrocgdqiq

Assessing Community Acceptance of Maternal Immunisation in Rural KwaZulu-Natal, South Africa: A Qualitative Investigation

Rujeko Chimukuche, Nothando Ngwenya, Janet Seeley, Petronella Nxumalo, Zama Nxumalo, Motlatso Godongwana, Nomasonto Radebe, Nellie Myburgh, Sunday Adedini, Clare Cutland
2022 Vaccines  
Despite the significant benefits of maternal immunisation, uptake remains low in many parts of the world. In this qualitative study, we aimed to assess the factors that influence pregnant women's decision to engage with maternal immunisation in rural KwaZulu-Natal, South Africa. We conducted in-depth interviews with a total of 28 purposively sampled pregnant women and key informants using semi-structured topic guides. Data analysis was conducted using a modified Health Belief Model framework
more » ... t included constructs of barriers to action, modifying factors of cue to action and perceived social norms. The findings show that traditional customs and institutional barriers such as low-quality health service delivery, long queues, and distance to the health facilities, immunisation vaccine stockouts and low levels of maternal knowledge influence the choice and decision to engage with maternal immunisation. Understanding health-related behaviours and addressing barriers to care is important in facilitating vaccination uptake. This study contributes to the understanding of maternal immunisation uptake in low-resource settings.
doi:10.3390/vaccines10030415 pmid:35335047 pmcid:PMC8951159 fatcat:pzemu7ds45gotjsibq6h6c4iam

Polyomaviruses-associated respiratory infections in HIV-infected and HIV-uninfected children

Marta C. Nunes, Zachary Kuschner, Zelda Rabede, Clare L. Cutland, Richard Madimabe, Locadiah Kuwanda, Keith P. Klugman, Peter V. Adrian, Shabir A. Madhi
2014 Journal of Clinical Virology  
Two recently discovered polyomaviruses (PyV), WU and KI, have been identified in respiratory-tract specimens from children with acute respiratory infections, although there are limited data in HIV-infected children. To determine the prevalence and clinical manifestations of WUPyV and KIPyV-associated lower respiratory tract infections (LRTIs) hospitalization in HIV-infected and -uninfected children; and probe the role of pneumococcal co-infection. Nasopharyngeal aspirates were collected from a
more » ... ohort of 39,836 children randomized to receive 9-valent pneumococcal conjugate vaccine (PCV9) or placebo when hospitalized for LRTIs, and were screened by PCR for WUPyV, KIPyV and other respiratory viruses. In placebo-recipients the prevalence of WUPyV was 6.3% (18/285) in HIV-infected and 13.9% (66/476) in HIV-uninfected children (p=0.002). In WUPyV-positive LRTIs HIV-infected children had lower oxygen saturation at admission and a higher case fatality rate (11.1% vs. 0%; p=0.04). KIPyV was identified in 10.2% (29/285) of HIV-infected and in 7.4% (35/476) of HIV-uninfected placebo-recipients with LRTIs (p=0.13). HIV-infected compared to HIV-uninfected children with KIPyV-positive LRTIs had lower oxygen saturation, higher respiratory rate and longer duration of hospitalization. Co-infections with other respiratory-viruses were detected in 65.5% of WUPyV-positive LRTIs and in 75.0% of KIPyV-positive LRTIs. Among HIV-uninfected children, there was a lower incidence of hospitalization for clinical pneumonia episodes in which KIPyV (80%; 95% CI: 41, 93) and WUPyV (49%; 95% CI: 9, 71) were identified among PCV9-recipients compared to placebo-recipients. Polyomaviruses were commonly identified in HIV-infected and -uninfected children hospitalized for LRTIs, frequently in association with other viruses and may contribute to the pathogenesis of pneumococcal pneumonia.
doi:10.1016/j.jcv.2014.10.013 pmid:25467863 pmcid:PMC7173307 fatcat:4lzk23i4hzhjtn7t3wftmou4wi

Vaccination with 10-valent pneumococcal conjugate vaccine in infants according to HIV status

Shabir A. Madhi, Anthonet Koen, Lisa Jose, Nadia van Niekerk, Peter V. Adrian, Clare Cutland, Nancy François, Javier Ruiz-Guiñazú, Juan-Pablo Yarzabal, Marta Moreira, Dorota Borys, Lode Schuerman
2017 Medicine  
Eligible participants were infants between and including 6-10 weeks of age at the time of the first vaccination, who were free of any known or suspected health problems (other than human immunodeficiency virus [HIV] infection or exposure) that would contraindicate the initiation of routine immunizations, for whom the investigator believed that their parents or guardians could and would comply with the protocol requirements, and with written informed consent obtained. Exclusion criteria included
more » ... the use of any investigational or non-registered product other than the study vaccines within 30 days before the first study dose, or any planned use during the study period; previous vaccination against or history of diphtheria, tetanus, pertussis, Haemophilus influenzae type b, rotavirus or S. pneumoniae; administration of immunoglobulins or any blood products since birth or planned administration during the study period; a family history of hereditary immunodeficiency; history of allergic disease or reactions likely to exacerbated by any component of the vaccines; weight <3rd percentile at Visit 1 (except for HIV-infected infants for which the decision of enrolment was left to the investigator's discretion); and moderately or severely symptomatic HIV (World Health Organisation stages III and IV). Additionally, study entry was delayed in case of disease at the time of enrolment, and vaccination was deferred in case of gastroenteritis within 7 days preceding planned vaccination.
doi:10.1097/md.0000000000005881 pmid:28079828 pmcid:PMC5266190 fatcat:s5nkhau6fffslnw6savgwzybpe

Obstetrics Risk Assessment: Evaluation of Selection Criteria for Vaccine Research Studies in Pregnant Women

Linda O. Eckert, Christine E. Jones, Alisa Kachikis, Azucena Bardají, Fernanda Tavares Da Silva, Judith Absalon, Caroline E. Rouse, Asma Khalil, Clare L. Cutland, Sonali Kochhar, Flor M. Munoz
2020 Vaccine  
Vaccines designed for use in pregnancy and vaccine trials specifically involving pregnant women are rapidly expanding. One of the key challenges in designing maternal immunization trials is that developing exclusion criteria requires understanding and quantifying the background risk for adverse pregnancy outcomes in the pregnancy being studied, which can occur independent of any intervention and be unrelated to vaccine administration. The Global Alignment of Immunization Safety Assessment in
more » ... gnancy (GAIA) project has developed and published case definitions and guidelines for data collection, analysis, and evaluation of maternal immunization safety in trials involving pregnant women. Complementing this work, we sought to understand how to best assess obstetric risk of adverse outcomes and differentiate it from the assessment of vaccine safety. Quantification of obstetric risk is based on prior and current obstetric, and maternal medical history. We developed a step-wise approach to evaluate and quantify obstetric and maternal risk factors in pregnancy based on review of published literature and guidelines, and critically assessed these factors in the context of designing inclusion and exclusion criteria for maternal vaccine studies. We anticipate this risk assessment evaluation may assist clinical trialists with study design decisions, including selection of exclusion criteria for vaccine trials involving pregnant women, consideration of sub-group classification, such as high or low risk subjects, or schedule considerations, such as preferred trimester of gestation for an intervention during pregnancy. Additionally, this tool may be utilized in data stratification at time of study analyses.
doi:10.1016/j.vaccine.2020.05.022 pmid:32448618 pmcid:PMC7211583 fatcat:kng5oas5hzgf5g6ljty2bugjum

HIV-Exposed Uninfected Infants Have Increased Regulatory T Cells That Correlate With Decreased T Cell Function

Emilie Jalbert, Kayla M. Williamson, Miranda E. Kroehl, Michael J. Johnson, Clare Cutland, Shabir A. Madhi, Marta C. Nunes, Adriana Weinberg
2019 Frontiers in Immunology  
HIV-exposed uninfected infants (HEU) are at higher risk of severe infections, hospitalizations and death compared with HIV-unexposed uninfected infants (HUU), but the immune deficit underlying it is not known. To address this gap, we investigated T cell functionality and its relationship to phenotypic profiles of T cells and antigen presenting cells (APC) in HEU and HUU. Methods: Blood mononuclear cells from 55 HEU and 16 HUU were stimulated with Staphylococcal Enterotoxin B (SEB) or mock for
more » ... h, and tested by flow cytometry for proliferation and expression of Th1, Th2, and regulatory (Treg) markers. In parallel, cells were phenotypically assessed for differentiation profiles of Treg, conventional T cell (Tconv) and APC in unstimulated cells. Results: HEU had lower CD4+ functional responses to SEB/mock and similar CD8+ responses compared with HUU. In the phenotypic T cell panel, HEU showed higher proportions of CD4+ and CD8+ Treg expressing IL10, FOXP3, and CD25; higher effector Tconv and Treg; and lower naïve and CD4+TGFβ+ Treg compared with HUU. In the phenotypic APC panel, HEU showed higher proportions of CD1c+ cDC2, CD123+ pDC, CD16+ inflammatory monocytes and cDC and higher expression of CD103 on CD1c-CD123-CD16-cDC1 compared with HUU. Regression analyses adjusted for HIV exposure and multiple comparisons showed that higher CD8+IL10+ and CD8+FOXP3+ Treg in unstimulated cells were associated with lower CD8+ T cell functional responses to SEB/mock. Functionality was not affected by Tconv differentiation, but higher APC activation in aggregate was associated with higher CD8+IL10+ Treg responses to SEB. Conclusions: T cell functionality was decreased in HEU compared with HUU. High CD8+ Treg proportions were the most important predictors of decreased T cell functionality in HEU and HUU.
doi:10.3389/fimmu.2019.00595 pmid:30972079 pmcid:PMC6445326 fatcat:xv63ajhdzref7lrblyx77wxmkm

Trivalent influenza vaccination randomized control trial of pregnant women and adverse fetal outcomes

Eric A.F. Simões, Marta C. Nunes, Phyllis Carosone-Link, Richard Madimabe, Justin R. Ortiz, Kathleen M. Neuzil, Keith P. Klugman, Clare L. Cutland, Shabir A. Madhi
2019 Vaccine  
The purpose of this study was to evaluate the association of influenza vaccine during pregnancy and adverse fetal outcomes. Preventing fetal death, low birth weight, small for gestational age birth and preterm birth are important potential effects of antenatal maternal influenza immunization for which there are conflicting data.
doi:10.1016/j.vaccine.2019.07.024 pmid:31331777 pmcid:PMC6694200 fatcat:wc2y37eukfczfgkquitru2asoa

Preparing for Disease X: Ensuring Vaccine Equity for Pregnant Women in Future Pandemics

Flor M. Munoz, Clare L. Cutland, Christine E. Jones, Beate Kampmann, Asma Khalil, Esperança Sevene, Andy Stergachis, Geeta K. Swamy, Gerald Voss, Ajoke Sobanjo-ter Meulen
2022 Frontiers in Medicine  
Disease X represents a yet unknown human pathogen which has potential to cause a serious international epidemic or pandemic. The COVID-19 pandemic has illustrated that despite being at increased risk of severe disease compared with the general population, pregnant women were left behind in the development and implementation of vaccination, resulting in conflicting communications and changing guidance about vaccine receipt in pregnancy. Based on the COVID-19 experience, the COVAX Maternal
more » ... ation Working Group have identified three key factors and five broad focus topics for consideration when proactively planning for a disease X pandemic, including 10 criteria for evaluating pandemic vaccines for potential use in pregnant women. Prior to any disease X pandemic, collaboration and coordination are needed to close the pregnancy data gap which is currently a barrier to gender equity in health innovation, which will aid in allowing timely access to life-saving interventions including vaccines for pregnant women and their infants.
doi:10.3389/fmed.2022.893292 pmid:35712117 pmcid:PMC9195576 fatcat:kmqcf3d2bnei7k7iwdu3qwqenu

Burden of Invasive Group B Streptococcus Disease and Early Neurological Sequelae in South African Infants

Ziyaad Dangor, Sanjay G. Lala, Clare L. Cutland, Anthonet Koen, Lisa Jose, Firdose Nakwa, Tanusha Ramdin, Joy Fredericks, Jeannette Wadula, Shabir A. Madhi, Jose Melo-Cristino
2015 PLoS ONE  
Introduction Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis. We aimed to evaluate the burden of invasive early-onset (0-6 days of life, EOD) and late-onset (7-89 days, LOD) GBS disease and subsequent neurological sequelae in infants from a setting with a high prevalence (29.5%) of HIV among pregnant women. Methods A case-control study was undertaken at three secondary-tertiary care public hospitals in Johannesburg. Invasive cases in infants <3 months age were
more » ... entified by surveillance of laboratories from November 2012 to February 2014. Neurodevelopmental screening was done in surviving cases and controls at 3 and 6 months of age. Results We identified 122 cases of invasive GBS disease over a 12 month period. Although the incidence (per 1,000 live births) of EOD was similar between HIV-exposed and HIV-unexposed infants (1.13 vs. 1.46; p = 0.487), there was a 4.67-fold (95%CI: 2.24-9.74) greater risk for LOD in HIV-exposed infants (2.27 vs. 0.49; p<0.001). Overall, serotypes Ia, Ib and III constituted 75.8% and 92.5% of EOD and LOD, respectively. Risk factors for EOD included offensive draining liquor (adjusted Odds Ratio: 27.37;), which was also a risk-factor for LOD (aOR: 3.49; 95%CI: 1.17-10.40). The overall case fatality rate among cases was 18.0%. The adjusted odds for neurological sequelae at 6 months age was 13.18-fold (95%CI: 1.44-120.95) greater in cases (13.2%) than controls (0.4%).
doi:10.1371/journal.pone.0123014 pmid:25849416 pmcid:PMC4388823 fatcat:i6ffc44gzrb6zhavbahl2le65i
« Previous Showing results 1 — 15 out of 94 results