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Microbial Genomics Sep 2023() is a leading vaccine-preventable cause of childhood invasive disease. Nigeria has the second highest pneumococcal disease burden globally, with an estimated...
() is a leading vaccine-preventable cause of childhood invasive disease. Nigeria has the second highest pneumococcal disease burden globally, with an estimated ~49 000 child deaths caused by pneumococcal infections each year. Ten-valent pneumococcal conjugate vaccine (GSK; PCV10) was introduced in December 2014 in a phased approach. However, few studies have characterized the disease-causing pneumococci from Nigeria. This study assessed the prevalence of serotypes, antibiotic susceptibility and genomic lineages using whole genome sequencing and identified lineages that could potentially escape PCV10 (GSK). We also investigated the potential differences in pneumococcal lineage features between children with and without sickle cell disease. A collection of 192 disease-causing pneumococcal isolates was obtained from Kano (=189) and Abuja (=3) states, Nigeria, between 1 January 2014 and 31 May 2018. The majority (99 %, 190/192) of specimens were recovered from children aged 5 years or under. Among them, 37 children had confirmed or traits of sickle cell disease. Our findings identified 25 serotypes expressed by 43 Global Pneumococcal Sequence Clusters (GPSCs) and 85 sequence types (STs). The most common serotypes were 14 (18 %, =35), 6B (16 %, =31), 1 (9 %, =17), 5 (9 %, =17) and 6A (9 %, =17); all except serotype 6A are included in PCV10 (GSK). PCV10 (SII; PNEUMOSIL) and PCV13 formulations include serotypes 6A and 19A which would increase the overall coverage from 67 % by PCV10 (GSK) to 78 and 82 %, respectively. The pneumococcal lineages were a mix of globally spreading and unique local lineages. Following the use of PCV10 (GSK), GPSC5 expressing serotype 6A, GPSC10 (19A), GPSC26 (12F and 46) and GPSC627 (9L) are non-vaccine type lineages that could persist and potentially expand under vaccine-selective pressure. Approximately half (52 %, 99/192) of the pneumococcal isolates were resistant to the first-line antibiotic penicillin and 44 % (85/192) were multidrug-resistant. Erythromycin resistance was very low (2 %, 3/192). There was no significant difference in clinical manifestation, serotype prevalence or antibiotic resistance between children with and without traits of or confirmed sickle cell disease. In summary, our findings show that a high percentage of the pneumococcal disease were caused by the serotypes that are covered by currently available vaccines. Given the low prevalence of resistance, macrolide antibiotics, such as erythromycin, should be considered as an option to treat pneumococcal disease in Nigeria. However, appropriate use of macrolide antibiotics should be vigilantly monitored to prevent the potential increase in macrolide resistance.
Topics: Humans; Child; Streptococcus pneumoniae; Nigeria; Anti-Bacterial Agents; Drug Resistance, Bacterial; Macrolides; Pneumococcal Infections; Erythromycin; Anemia, Sickle Cell; Protein Synthesis Inhibitors
PubMed: 37712828
DOI: 10.1099/mgen.0.001094 -
Vaccines Jun 2024In patients with cancer, tumor- and treatment-induced immunosuppression are responsible for a four-fold increase in morbidity and mortality caused by influenza and...
Hospital-Based Influenza and Pneumococcal Vaccination for Cancer Patients on Active Treatment and Their Family Members during the COVID-19 Pandemic in Italy: A Single-Center Experience.
In patients with cancer, tumor- and treatment-induced immunosuppression are responsible for a four-fold increase in morbidity and mortality caused by influenza and invasive infections compared to the general population. The main oncology societies strongly recommend vaccination in patients with cancer to prevent these infections. However, vaccine hesitancy is a main concern in this population. The aim of this study was to assess the feasibility of in-hospital vaccination for patients under anticancer treatment and their family members (FMs) against influenza and pneumococcal infections during the COVID-19 pandemic in order to increase vaccine coverage. This was a single-center, prospective, observational study conducted at the Department of Oncology of Luigi Sacco University Hospital (Milan, Italy) between October 2020 and April 2021. The main primary outcome was the incidence of influenza-like illness (ILI) and pneumococcal infections. The main secondary outcome was safety. A total of 341 subjects were enrolled, including 194 patients with cancer and 147 FMs. The incidence of ILI was higher among patients than among FMs (9% vs. 2.7%, OR 3.92, = 0.02). Moreover, two subjects were diagnosed with pneumococcal pneumonia. The most frequent vaccine-related AEs were pain in the injection site (31%) and fatigue (8.7%). In conclusion, this hospital-based vaccination strategy was feasible during the COVID-19 pandemic, representing a potential model to maximize vaccine coverage during a public health emergency.
PubMed: 38932371
DOI: 10.3390/vaccines12060642 -
The Lancet. Infectious Diseases Sep 2023Non-pharmaceutical interventions affected the circulation of and illness due to endemic respiratory pathogens during the COVID-19 pandemic. We investigated the incidence... (Observational Study)
Observational Study
All-cause and pathogen-specific lower respiratory tract infection hospital admissions in children younger than 5 years during the COVID-19 pandemic (2020-22) compared with the pre-pandemic period (2015-19) in South Africa: an observational study.
BACKGROUND
Non-pharmaceutical interventions affected the circulation of and illness due to endemic respiratory pathogens during the COVID-19 pandemic. We investigated the incidence of admissions to hospital for overall and specific pathogen-associated lower respiratory tract infection (LRTI) during the COVID-19 pandemic compared with incidence in the pre-pandemic period.
METHODS
In this observational study, we analysed surveillance data for children younger than 5 years from two public hospitals in Soweto, South Africa, for all-cause LRTI, respiratory syncytial virus (RSV), influenza, human metapneumovirus, and Bordetella pertussis from Jan 1, 2015 to Dec 31, 2022. Data were obtained from an electronic database that includes information for all admissions to the general paediatric wards at the two hospitals, automatically identified by a computer program. We excluded children admitted to hospital with incidental SARS-CoV-2 infection or COVID-19 without LRTI diagnosis. Incidence during COVID-19 pandemic years (2020, 2021, and 2022) were compared with pre-pandemic rates (2015-19).
FINDINGS
Overall, there were 42 068 all-cause hospital admissions, including 18 303 all-cause LRTI hospital admissions, from Jan 1, 2015, to Dec 31, 2022, 17 822 (42·4%) of whom were female, 23 893 (57·0%) were male, and 353 (0·8%) had missing data. All-cause LRTI incidence risk ratio (IRR) was 30% lower in 2020 (IRR 0·70, 95% CI 0·67-0·74) and 13% lower in 2021 (0·87, 0·83-0·91), but 16% higher in 2022 (1·16, 1·11-1·21) compared with the pre-pandemic period. Furthermore, compared with the pre-pandemic period, incidence of RSV-associated LRTI (0·52, 0·45-0·58), influenza-associated LRTI (0·05, 0·02-0·11), and pulmonary tuberculosis (0·52, 0·41-0·65) were lower in 2020, with similar trends observed for human-metapneumovirus-associated LRTI, pertussis, and invasive pneumococcal disease (IPD). Compared with the pre-pandemic period, by 2022, RSV-associated LRTI incidence was similar (1·04, 0·95-1·14) and influenza-associated LRTI showed a non-significant increase (1·14, 0·92-1·39), whereas incidence remained lower for tuberculosis (0·79, 0·65-0·94) and IPD (0·51, 0·24-0·99). In 2022, the incidence of COVID-19-associated LRTI hospital admission (65 per 100 000 children younger than 5 years) was lower than pre-pandemic RSV-associated LRTI (0·23, 0·19-0·27) but higher than pre-pandemic influenza-associated LRTI (1·19, 0·97-1·45), although the difference was not significant. All-cause LRTI death in 2022 (57 per 100 000 children younger than 5 years) was 28% higher than in the pre-pandemic period (1·28, 1·03-1·58).
INTERPRETATION
The higher incidence of all-cause LRTI admissions to hospital in 2022 compared with the pre-pandemic period is partly due to ongoing COVID-19 admission to hospital, and could worsen if other endemic respiratory pathogens revert to pre-pandemic incidence. Interventions, including the introduction of vaccines for people who are pregnant that aim to prevent RSV and possibly COVID-19 in young children, are warranted.
FUNDING
The Bill & Melinda Gates Foundation.
Topics: Pregnancy; Humans; Male; Female; Child; Infant; Child, Preschool; Pandemics; South Africa; Influenza, Human; COVID-19; SARS-CoV-2; Respiratory Tract Infections; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Pneumococcal Infections; Hospitals
PubMed: 37141913
DOI: 10.1016/S1473-3099(23)00200-1 -
Medicina (Kaunas, Lithuania) Oct 2023is a bacterial species often associated with the occurrence of community-acquired pneumonia (CAP). CAP refers to a specific kind of pneumonia that occurs in individuals... (Review)
Review
is a bacterial species often associated with the occurrence of community-acquired pneumonia (CAP). CAP refers to a specific kind of pneumonia that occurs in individuals who acquire the infection outside of a healthcare setting. It represents the leading cause of both death and morbidity on a global scale. Moreover, the declaration of as one of the 12 leading pathogens was made by the World Health Organization (WHO) in 2017. Antibiotics like -lactams, macrolides, and fluoroquinolones are the primary classes of antimicrobial medicines used for the treatment of infections. Nevertheless, the efficacy of these antibiotics is diminishing as a result of the establishment of resistance in against these antimicrobial agents. In 2019, the WHO declared that antibiotic resistance was among the top 10 hazards to worldwide health. It is believed that penicillin-binding protein genetic alteration causes -lactam antibiotic resistance. Ribosomal target site alterations and active efflux pumps cause macrolide resistance. Numerous factors, including the accumulation of mutations, enhanced efflux mechanisms, and plasmid gene acquisition, cause fluoroquinolone resistance. Furthermore, despite the advancements in pneumococcal vaccinations and artificial intelligence (AI), it is not feasible for individuals to rely on them indefinitely. The ongoing development of AI for combating antimicrobial resistance necessitates more research and development efforts. A few strategies can be performed to curb this resistance issue, including providing educational initiatives and guidelines, conducting surveillance, and establishing new antibiotics targeting another part of the bacteria. Hence, understanding the resistance mechanism of may aid researchers in developing a more efficacious antibiotic in future endeavors.
Topics: Humans; Anti-Bacterial Agents; Streptococcus pneumoniae; Fluoroquinolones; beta-Lactams; Macrolides; Artificial Intelligence; Drug Resistance, Bacterial; Pneumonia; Anti-Infective Agents; Community-Acquired Infections
PubMed: 38003976
DOI: 10.3390/medicina59111927 -
Bulletin of Experimental Biology and... Sep 2023The aim of the study was to evaluate the activity of Raphamin in a model of non-lethal pneumococcal infection caused by Streptococcus pneumoniae 3 in BALB/c mice. The...
The aim of the study was to evaluate the activity of Raphamin in a model of non-lethal pneumococcal infection caused by Streptococcus pneumoniae 3 in BALB/c mice. The drug or placebo was administered intragastrically 3 days prior to infection, 2 h before and 2 h post infection, and then for 3 full days, alone or in combination with antibiotic (amoxicil-lin/clavulanic acid). Raphamin monotherapy significantly decreased bacterial load in the lungs in comparison with placebo (p<0.05) which was comparable to the effect in antibiotic alone or combined with Raphamin. Raphamin prevented reproduction of Streptococcus pneumoniae in the lower respiratory tract and its combination with the antibiotic was safe and did not reduce the efficacy of amoxicillin/clavulanic acid.
Topics: Mice; Animals; Pneumococcal Infections; Streptococcus pneumoniae; Anti-Bacterial Agents; Amoxicillin-Potassium Clavulanate Combination; Clavulanic Acid
PubMed: 37861906
DOI: 10.1007/s10517-023-05919-7 -
Gerontology 2024Older people living in long-term care facilities represent a particularly vulnerable segment of the population, who disproportionately bear the burden of infectious... (Review)
Review
BACKGROUND
Older people living in long-term care facilities represent a particularly vulnerable segment of the population, who disproportionately bear the burden of infectious diseases, as recently highlighted by the COVID-19 pandemic.
SUMMARY
Older long-term care residents typically cumulate several risk factors for infection and experience serious life-threatening outcomes once infected. These common infections are often compounded by the collective living environment, where it is more difficult to contain the spread of infection. Moreover, the staff may represent an additional reservoir of potential infection and mode of transmission. In this paper, we review the burden of infectious respiratory diseases in residents in long-term care and discuss the potential gains from higher vaccine coverage in this older and most vulnerable population but also from higher vaccine coverage among the facility staff. We highlight the compelling need to integrate specific vaccine recommendations for residents of long-term care into national vaccination schedules, as well as the need to include vaccination campaigns in routine protocols for infection control. Surveillance, reporting, hygiene, and individual protective measures remain key aspects in basic infection control, both in ordinary times and during epidemics.
KEY MESSAGE
Vaccination of residents in long-term care facilities against respiratory diseases including influenza, pneumococcal disease, pertussis, and COVID is a simple, inexpensive, and effective means to reduce the burden of infection in this segment of the population.
Topics: Humans; Aged; Long-Term Care; Pandemics; Influenza, Human; Influenza Vaccines; Vaccination
PubMed: 38091961
DOI: 10.1159/000534998 -
Human Vaccines & Immunotherapeutics Aug 2023This study assessed the cost-effectiveness of the 20-valent pneumococcal conjugate vaccine (PCV20) in Canadian infants aged <2 years versus the standard of care...
This study assessed the cost-effectiveness of the 20-valent pneumococcal conjugate vaccine (PCV20) in Canadian infants aged <2 years versus the standard of care (SoC), a 13-valent pneumococcal conjugate vaccine (PCV13), or a potential 15-valent pneumococcal conjugate vaccine (PCV15). A decision-analytic Markov model was developed to compare PCV20 with PCV13 or PCV15 in a 2 + 1 schedule over 10 years. Vaccine effect estimates (direct and indirect) across all ages were informed by PCV13 clinical effectiveness and impact studies as well as PCV7 efficacy studies. Epidemiologic, clinical, health state utilities, utility decrements, cost per event, and list price data were from Canadian sources where available. Clinical and economic outcomes related to invasive pneumococcal disease (IPD), hospitalized and non-hospitalized pneumonia, and simple and complex otitis media (OM) were calculated for each strategy. Cost-effectiveness was evaluated from the publicly funded healthcare system perspective. Over 10 years, PCV20 versus PCV13 was estimated to avert over 11,000 IPD cases, 316,000 hospitalized and non-hospitalized pneumonia cases, 335,000 simple and complex OM cases, and 15,000 deaths, resulting in cost savings of over 3.2 billion Canadian dollars (CAD) and 47,000 more quality-adjusted life years (i.e. dominant strategy). Compared with PCV15, PCV20 was estimated to result in over 1.4 billion CAD in cost savings and 21,000 more QALYs (i.e. dominant strategy). PCV20 was dominant over both PCV13 and PCV15. Given broader serotype coverage, substantial incremental benefits and cost-savings, PCV20 should be considered as a replacement for the SoC in the publicly funded Canadian infant immunization program.
Topics: Infant; Humans; Child; Cost-Effectiveness Analysis; Vaccines, Conjugate; Cost-Benefit Analysis; Canada; Pneumococcal Infections; Pneumococcal Vaccines; Pneumonia; Otitis Media
PubMed: 37771288
DOI: 10.1080/21645515.2023.2257426 -
PloS One 2024While the 23-valent pneumococcal polysaccharide vaccine (PPV23) has demonstrated its role in preventing severe pneumococcal disease, its impact on more non-specific...
BACKGROUND
While the 23-valent pneumococcal polysaccharide vaccine (PPV23) has demonstrated its role in preventing severe pneumococcal disease, its impact on more non-specific conditions like acute respiratory tract infection (ARI) and lower respiratory tract infections (LRTI) remains unclear. We aimed to investigate the role of PPV23 in prevention of presentations for ARI and LRTI and related antibiotic prescriptions among older adults in primary care.
METHODS
Using a nationwide general practice dataset, we followed a cohort of regularly attending patients aged ≥65 years from 1 January 2014 until 31 December 2018 for presentations for ARI, LRTI, and related antibiotic prescriptions. Associations between PPV23 receipt and each outcome were assessed using a multiple failures survival model to estimate hazard ratios (HR) adjusted for age, sex, socioeconomic status, and various health measures.
RESULTS
A cohort of 75,264 patients aged ≥65 years (mean 75.4, 56% female) in 2014 was followed. The incidence of presentations for ARI, ARI-related antibiotic prescription, LRTI, and LRTI-related antibiotic prescription was 157.6, 76.0, 49.6, and 24.3 per 1000 person-years, respectively. Recent PPV23 vaccine receipt was associated with a small reduction in ARI presentations (adjusted HR vaccinated vs. unvaccinated 0.96; 95%CI 0.94-0.98; p = 0.002); however, there was no reduction in ARI-related antibiotic prescription, LRTI presentation, nor LRTI-related antibiotic prescription (adjusted HR were 0.99[95%CI 0.96-1.03], 1.04[95%CI 0.99-1.09], 1.07[95%CI 1.00-1.14]).
CONCLUSION
PPV23 vaccination in older adults may result in a small reduction in the incidence of total ARI presentations in primary care. However, the effect is small and residual confounding cannot be excluded.
Topics: Humans; Female; Aged; Male; Anti-Bacterial Agents; Respiratory Tract Infections; Streptococcus pneumoniae; Vaccination; Pneumococcal Vaccines; Primary Health Care; Pneumococcal Infections
PubMed: 38635814
DOI: 10.1371/journal.pone.0299924 -
Cell Reports Mar 2024Pneumolysin (Ply) is an indispensable cholesterol-dependent cytolysin for pneumococcal infection. Although Ply-induced disruption of pneumococci-containing endosomal...
Pneumolysin (Ply) is an indispensable cholesterol-dependent cytolysin for pneumococcal infection. Although Ply-induced disruption of pneumococci-containing endosomal vesicles is a prerequisite for the evasion of endolysosomal bacterial clearance, its potent activity can be a double-edged sword, having a detrimental effect on bacterial survivability by inducing severe endosomal disruption, bactericidal autophagy, and scaffold epithelial cell death. Thus, Ply activity must be maintained at optimal levels. We develop a highly sensitive assay to monitor endosomal disruption using NanoBiT-Nanobody, which shows that the pneumococcal sialidase NanA can fine-tune Ply activity by trimming sialic acid from cell-membrane-bound glycans. In addition, oseltamivir, an influenza A virus sialidase inhibitor, promotes Ply-induced endosomal disruption and cytotoxicity by inhibiting NanA activity in vitro and greater tissue damage and bacterial clearance in vivo. Our findings provide a foundation for innovative therapeutic strategies for severe pneumococcal infections by exploiting the duality of Ply activity.
Topics: Humans; Neuraminidase; Streptococcus pneumoniae; Streptolysins; Pneumococcal Infections; Bacterial Proteins
PubMed: 38483905
DOI: 10.1016/j.celrep.2024.113962 -
Vaccine Jul 2023This phase III study evaluated safety, tolerability, and immunogenicity of V114 (15-valent pneumococcal conjugate vaccine) in Japanese infants. V114 contains all 13... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
This phase III study evaluated safety, tolerability, and immunogenicity of V114 (15-valent pneumococcal conjugate vaccine) in Japanese infants. V114 contains all 13 serotypes in PCV13 plus additional serotypes 22F and 33F.
METHODS
Healthy Japanese infants were randomized to receive three primary doses of V114 or PCV13 (dose 1 at 2-6 months of age; doses 2 and 3 ≥ 27 days after prior dose), plus a toddler dose at 12-15 months of age. Adverse events (AEs) were collected on Days 1-14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-dose 3, pre-dose 4, and 30 days post-dose 4. Primary objectives included non-inferiority of V114 to PCV13 for the 13 shared serotypes based on serotype-specific IgG response rates (IgG ≥ 0.35 μg/mL) and geometric mean concentration (GMC) ratios, and for serotypes 22F and 33F based on IgG response rates and compared with the lowest response of any serotype in the PCV13 group, at 30 days post-dose 3.
RESULTS
Overall, 694 infants were randomized to V114 (n = 347) or PCV13 (n = 347). Proportions of participants with solicited and serious AEs were comparable between vaccination groups. V114 met non-inferiority criteria for all 13shared serotypes, based on difference in proportion of responders (lower bound of two-sided 95 % confidence interval [CI] > -10.0) and IgG GMC ratios (V114/PCV13, lower bound of two-sided 95 % CI > 0.5) at 30 days post-dose 3. The non-inferiority criterion based on IgG response rates was met for serotype 22F, but narrowly missed for serotype 33F (90.9 %, lower bound of two-sided 95 % CI -10.6).
CONCLUSION
In Japanese infants, a four-dose series of V114 was generally well tolerated. Compared with PCV13, V114 provided non-inferior immune responses to the 13 shared serotypes and higher immune responses to serotype 22F and 33F post-primary series.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT04384107; EudraCT 2019-003644-68.
Topics: Humans; Infant; Vaccines, Conjugate; Pneumococcal Infections; East Asian People; Antibodies, Bacterial; Immunoglobulin G; Pneumococcal Vaccines; Immunogenicity, Vaccine
PubMed: 37344262
DOI: 10.1016/j.vaccine.2023.05.064