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- Martin, DP, et al.
(författare)
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Selection analysis identifies unusual clustered mutational changes in Omicron lineage BA.1 that likely impact Spike function
- 2022
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Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Among the 30 non-synonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (i) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (ii) interactions of Spike with ACE2 receptors, and (iii) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any genomes within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron over all previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected.
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- Harrison, Lee H, et al.
(författare)
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The global Meningococcal initiative : recommendations for reducing the global burden of meningococcal disease
- 2011
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 29:18, s. 3363-3371
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Tidskriftsartikel (refereegranskat)abstract
- The Global Meningococcal Initiative (GMI) is composed of an international group of scientists, clinicians and public health officials with expertise in meningococcal immunology, epidemiology and prevention. The primary goal of the GMI is the promotion of the global prevention of invasive meningococcal disease through education and research. The GMI members reviewed global meningococcal disease epidemiology, immunization strategies, and research needs. Over the past decade, substantial advances in meningococcal vaccine development have occurred and much has been learned about prevention from countries that have incorporated meningococcal vaccines into their immunization programs. The burden of meningococcal disease is unknown for many parts of the world because of inadequate surveillance, which severely hampers evidence-based immunization policy. As the field of meningococcal vaccine development advances, global surveillance for meningococcal disease needs to be strengthened in many regions of the world. For countries with meningococcal vaccination policies, research on vaccine effectiveness and impact, including indirect effects, is crucial for informing policy decisions. Each country needs to tailor meningococcal vaccination policy according to individual country needs and knowledge of disease burden. Innovative approaches are needed to introduce and sustain meningococcal vaccination programs in resource-poor settings with a high incidence of meningococcal disease.
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- Nzenze, S. A., et al.
(författare)
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Temporal association of infant immunisation with pneumococcal conjugate vaccine on the ecology of Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus nasopharyngeal colonisation in a rural South African community
- 2014
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Ingår i: Vaccine. - : Elsevier. - 0264-410X .- 1873-2518. ; 32:42, s. 5520-5530
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Tidskriftsartikel (refereegranskat)abstract
- Background: Immunisation of children with pneumococcal conjugate vaccines (PCV) may affect the bacterial-ecology of the nasopharynx, including colonisation by Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus. The aim of this study was to evaluate the effect of infant PCVimmunisation on the nasopharyngeal ecology of these potentially pathogenic bacteria in a rural African setting. Methods: Two cross sectional surveys were undertaken from May to October in 2009 (Period-1) which coincided with the introduction of 7-valent PCV (PCV7) and in May-October 2011 (Period-2). Consenting household members, where there was a child <2 years of age in residence, had nasopharyngeal swabs undertaken for culture. Results: From Period-1 to Period-2 in children 0-2 years and 3-12 years, prevalence of overall S. pneumoniae colonisation decreased from 74.9% to 67.0% (p < 0.001) and H. influenzae declined among children 3-12 years (55.1-45.3%, p < 0.001) but not among those <2 years. The prevalence of S. aureus remained unchanged in all children. Competitive associations were found between S. pneumoniae and S. aureus and between H. influenzae and S. aureus among children. In individuals >12 years, the prevalence of colonisation decreased from 11.2% to 6.8%, 16.7% to 8.8% and 31.2% to 23.7% for S. pneumoniae, H. influenzae and S. aureus, respectively; p < 0.001 for all comparions. Synergistic relationships for S. aureus with H. influenzae and S. pneumoniae were observed in both periods among this group.
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- Ayeni, Oluwatosin A., et al.
(författare)
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Mortality in children aged <5 years with severe acute respiratory illness in a high HIV-prevalence urban and rural areas of South Africa, 2009–2013
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Severe acute respiratory illness (SARI) is an important cause of mortality in young children, especially in children living with HIV infection. Disparities in SARI death in children aged <5 years exist in urban and rural areas.Objective: To compare the factors associated with in-hospital death among children aged <5 years hospitalized with SARI in an urban vs. a rural setting in South Africa from 2009–2013.Methods: Data were collected from hospitalized children with SARI in one urban and two rural sentinel surveillance hospitals. Nasopharyngeal aspirates were tested for ten respiratory viruses and blood for pneumococcal DNA using polymerase chain reaction. We used multivariable logistic regression to identify patient and clinical characteristics associated with in-hospital death.Results: From 2009 through 2013, 5,297 children aged <5 years with SARI-associated hospital admission were enrolled; 3,811 (72%) in the urban and 1,486 (28%) in the rural hospitals. In-hospital case-fatality proportion (CFP) was higher in the rural hospitals (6.9%) than the urban hospital (1.3%, p<0.001), and among HIV-infected than the HIV-uninfected children (9.6% vs. 1.6%, p<0.001). In the urban hospital, HIV infection (odds ratio (OR):11.4, 95% confidence interval (CI):5.4–24.1) and presence of any other underlying illness (OR: 3.0, 95% CI: 1.0–9.2) were the only factors independently associated with death. In the rural hospitals, HIV infection (OR: 4.1, 95% CI: 2.3–7.1) and age <1 year (OR: 3.7, 95% CI: 1.9–7.2) were independently associated with death, whereas duration of hospitalization ≥5 days (OR: 0.5, 95% CI: 0.3–0.8) and any respiratory virus detection (OR: 0.4, 95% CI: 0.3–0.8) were negatively associated with death.Conclusion: We found that the case-fatality proportion was substantially higher among children admitted to rural hospitals and HIV infected children with SARI in South Africa. While efforts to prevent and treat HIV infections in children may reduce SARI deaths, further efforts to address health care inequality in rural populations are needed.
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- Cohen, Adam L, et al.
(författare)
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Parainfluenza Virus Infection Among Human Immunodeficiency Virus (HIV)-Infected and HIV-Uninfected Children and Adults Hospitalized for Severe Acute Respiratory Illness in South Africa, 2009-2014
- 2015
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Ingår i: Open forum infectious diseases. - : Oxford University Press. - 2328-8957. ; 2:4
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Tidskriftsartikel (refereegranskat)abstract
- Background. Parainfluenza virus (PIV) is a common cause of acute respiratory tract infections, but little is known about PIV infection in children and adults in Africa, especially in settings where human immunodeficiency virus (HIV) prevalence is high. Methods. We conducted active, prospective sentinel surveillance for children and adults hospitalized with severe acute respiratory illness (SARI) from 2009 to 2014 in South Africa. We enrolled controls (outpatients without febrile or respiratory illness) to calculate the attributable fraction for PIV infection. Respiratory specimens were tested by multiplex real-time reverse-transcription polymerase chain reaction assay for parainfluenza types 1, 2, and 3. Results. Of 18 282 SARI cases enrolled, 1188 (6.5%) tested positive for any PIV type: 230 (19.4%) were type 1; 168 (14.1%) were type 2; 762 (64.1%) were type 3; and 28 (2.4%) had coinfection with 2 PIV types. After adjusting for age, HIV serostatus, and respiratory viral coinfection, the attributable fraction for PIV was 65.6% (95% CI [ confidence interval], 47.1-77.7); PIV contributed to SARI among HIV-infected and -uninfected children < 5 years of age and among individuals infected with PIV types 1 and 3. The observed overall incidence of PIV-associated SARI was 38 (95% CI, 36-39) cases per 100 000 population and was highest in children < 1 year of age (925 [ 95% CI, 864-989] cases per 100 000 population). Compared with persons without HIV, persons with HIV had an increased relative risk of PIV hospitalization (9.4; 95% CI, 8.5-10.3). Conclusions. Parainfluenza virus causes substantial severe respiratory disease in South Africa among children < 5 years of age, especially those that are infected with HIV.
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| 9. |
- Cohen, Cheryl, et al.
(författare)
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Epidemiology of Acute Lower Respiratory Tract Infection in HIV-Exposed Uninfected Infants
- 2016
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Ingår i: Pediatrics. - : American Academy of Pediatrics. - 0031-4005 .- 1098-4275. ; 137:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Increased morbidity and mortality from lower respiratory tract infection (LRTI) has been suggested in HIV-exposed uninfected (HEU) children; however, the contribution of respiratory viruses is unclear. We studied the epidemiology of LRTI hospitalization in HIV-unexposed uninfected (HUU) and HEU infants aged <6 months in South Africa. METHODS: We prospectively enrolled hospitalized infants with LRTI from 4 provinces from 2010 to 2013. Using polymerase chain reaction, nasopharyngeal aspirates were tested for 10 viruses and blood for pneumococcal DNA. Incidence for 2010-2011 was estimated at 1 site with population denominators. RESULTS: We enrolled 3537 children aged <6 months. HIV infection and exposure status were determined for 2507 (71%), of whom 211 (8%) were HIV infected, 850 (34%) were HEU, and 1446 (58%) were HUU. The annual incidence of LRTI was elevated in HEU (incidence rate ratio [IRR] 1.4; 95% confidence interval [CI] 1.3-1.5) and HIV infected (IRR 3.8; 95% CI 3.3-4.5), compared with HUU infants. Relative incidence estimates were greater in HEU than HUU, for respiratory syncytial virus (RSV; IRR 1.4; 95% CI 1.3-1.6) and human metapneumovirus-associated (IRR 1.4; 95% CI 1.1-2.0) LRTI, with a similar trend observed for influenza (IRR 1.2; 95% CI 0.8-1.8). HEU infants overall, and those with RSV-associated LRTI had greater odds (odds ratio 2.1, 95% CI 1.1-3.8, and 12.2, 95% CI 1.7-infinity, respectively) of death than HUU. CONCLUSIONS: HEU infants were more likely to be hospitalized and to die in-hospital than HUU, including specifically due to RSV. This group should be considered a high-risk group for LRTI.
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| 10. |
- Madhi, Shabir A., et al.
(författare)
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Residual colonization by vaccine serotypes in rural South Africa four years following initiation of pneumococcal conjugate vaccine immunization
- 2020
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Ingår i: Expert Review of Vaccines. - : Taylor & Francis. - 1476-0584 .- 1744-8395. ; 19:4, s. 383-393
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Tidskriftsartikel (refereegranskat)abstract
- Background: We evaluated pneumococcal colonization in children and adults between the time of 7-valent pneumococcal conjugate vaccine (PCV) introduction in the immunization program in 2009 to two years after transitioning to PCV13 in 2011.Methods: Community-based carriage surveillance was undertaken between May-November 2013 (Period-3), with similar surveys in 2009 (Period-1) and 2011 (Period-2). Households with children below two years had a similar probability of being sampled in all surveys. Nasopharyngeal swabs were processed using standard methods and serotyped by Quellung.Results: In children>9-59 months old, overall pneumococcal colonization prevalence declined from 81.8% in Period-1 to 65.0% in Period-3 (p<0.001). Reductions of 70% (41.2% vs. 13.6%) in PCV7-serotypes colonization and 66% (15.3% vs. 4.4%) for the six additional PCV13-serotypes (PCV13-add6VT) were observed. There was, however, high residual colonization by PCV7-serotypes 19F (14.9% vs. 6.3%) and 23F (8.5% vs. 4.1%), despite reduction of 57% and 52%, respectively. Among individuals>12 years of age, there was 61% reduction in PCV7-serotype colonization (3.1% vs. 1.3%) and 75% decrease for PCV13-add6VT (2.1% vs. 0.6%) between Period-1 and Period-3.Conclusions: The residual prevalence of serotypes 19F and 23F, four years after introducing PCV in the South Africa, suggests ongoing community transmission and transient vaccine effects.
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