Epidemiology of community-acquired pneumonia caused by S treptococcus pneumoniae in older adults: a narrative review.

PURPOSE OF REVIEW: This review covers updated perspectives on different aspects of pneumococcal community-acquired pneumonia (pCAP), including the epidemiology, clinical presentation, risk factors, antibiotic treatment, and existing preventive strategies in older adults. RECENT FINDINGS: pCAP remains the most prevalent condition among lower respiratory tract infections in the older adults according to Global Burden of Diseases 2019. Older adults can display atypical symptoms such as confusion, general clinical deterioration, new onset of and exacerbation of underlying illness that might trigger clinical suspicion of pCAP. Older adults with pCAP often experience increased disease severity and a higher risk of pulmonary complications compared with younger individuals, owing to age-related changes in immunity and a higher prevalence of comorbidities. Vaccination stands fundamental for prevention, emphasizing the need for effective immunization strategies, specifically tailored for older adults. There is a pressing need to reinforce efforts aimed at boosting pneumococcal vaccination rates. SUMMARY: Despite a high morbidity and mortality, the burden of pCAP, in particular hospital admission and occurrence of invasive infections, among the elderly population is not sufficiently documented. This review findings emphasize the substantial burden of pCAP in this vulnerable population, driven by factors such as advancing age and underlying comorbidities. The emergence of antibiotic-resistant pneumococcal strains further complicates treatment decisions and highlights the importance of tailored approaches for managing pCAP in older adults.

Hemagglutinin Stalk Antibody Responses Following Trivalent Inactivated Influenza Vaccine Immunization of Pregnant Women and Association With Protection From Influenza Virus Illness.

BACKGROUND: The conserved, immuno-subdominant influenza virus hemagglutinin (HA) stalk region is a potential universal group-specific influenza virus vaccine epitope. We analyzed antibody responses to H1 hemagglutinin stalk domain (H1/stalk) following trivalent influenza inactivated vaccine (IIV3) immunization in pregnant women, and association with protection against influenza virus illness. METHODS: One hundred forty-five human immunodeficiency virus (HIV)-uninfected pregnant women (68 IIV3 and 77 placebo recipients) and 140 pregnant women with HIV infection (72 IIV3 and 68 placebo recipients) were independently randomized in placebo-controlled efficacy trials of IIV3. Plasma samples were tested for H1/stalk immunoglobulin G (IgG) and hemagglutination inhibition (HAI) antibodies prevaccination and 1 month postvaccination. Women had weekly surveillance for influenza illness, confirmed by polymerase chain reaction. RESULTS: Increases in H1/stalk IgG (and HAI) antibody levels were elicited post-IIV3, with responses being higher in HIV-uninfected women than in women living with HIV. Among HIV-uninfected vaccinees, there was no correlation (postvaccination) between H1/stalk and HAI antibody responses, whereas a strong correlation was observed in vaccinees with HIV. The H1/stalk IgG concentration was lower among women developing A/H1N1 illness (85.3 arbitrary units [AU]/mL) than those without A/H1N1 illness (219.6 AU/mL; P = .001). H1/stalk IgG concentration ≥215 AU/mL was associated with 90% lower odds (odds ratio, 0.09; P = .005) of A/H1N1 illness. Also, H1/stalk IgG was significantly lower among women with influenza B illness (93.9 AU/mL) than among their counterparts (215.5 AU/mL) (P = .04); however, no association was observed after adjusting for HAI titers. CONCLUSIONS: H1/stalk IgG concentration was associated with lower odds for A/H1N1 influenza virus illness, indicating its potential as an epitope for a universal vaccine against group 1 influenza virus.

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.

Effectiveness of Influenza Vaccination of Pregnant Women for Prevention of Maternal and Early Infant Influenza-Associated Hospitalizations in South Africa: A Prospective Test-Negative Study.

Background: Influenza vaccination during pregnancy reduces influenza-associated illness in the women and their infants, but effectiveness estimates against influenza-associated hospitalization are limited and lacking from settings with high human immunodeficiency virus (HIV) infection prevalence. We assessed the effect of maternal vaccination in HIV-uninfected women and women with HIV in preventing influenza-associated hospitalizations in infants and the women. Methods: During 2015-2018, influenza vaccination campaigns targeting pregnant women were augmented at selected antenatal clinics; these were coupled with prospective hospital-based surveillance for acute respiratory or febrile illness in infants aged <6 months and cardiorespiratory illness among pregnant or postpartum women. Vaccine effectiveness (VE) was assessed using a test-negative case-control study. Results: Overall, 71 influenza-positive and 371 influenza-negative infants were included in the analysis; mothers of 26.8% of influenza-positive infants were vaccinated during pregnancy compared with 35.6% of influenza-negative infants, corresponding to an adjusted VE (aVE) of 29.0% (95% confidence interval [CI], -33.6% to 62.3%). When limited to vaccine-matched strains, aVE was 65.2% (95% CI, 11.7%-86.3%). For maternal hospitalizations, 56 influenza-positive and 345 influenza-negative women were included in the analysis, with 28.6% of influenza-positive women being vaccinated compared with 38.3% of influenza-negatives, for an aVE of 46.9% (95% CI, -2.8% to 72.5%). Analysis restricted to HIV-uninfected women resulted in 82.8% (95% CI, 40.7%-95.0%) aVE. No significant aVE (-32.5% [95% CI, -208.7% to 43.1%]) was detected among women with HIV. Conclusions: Influenza vaccination during pregnancy prevented influenza-associated hospitalizations among young infants when infected with vaccine strains and among HIV-uninfected women.

Efficacy, duration of protection, birth outcomes, and infant growth associated with influenza vaccination in pregnancy: a pooled analysis of three randomised controlled trials.

BACKGROUND: Maternal influenza immunisation can reduce morbidity and mortality associated with influenza infection in pregnant women and young infants. We aimed to determine the vaccine efficacy of maternal influenza immunisation against maternal and infant PCR-confirmed influenza, duration of protection, and the effect of gestational age at vaccination on vaccine efficacy, birth outcomes, and infant growth up to 6 months of age. METHODS: We did a pooled analysis of three randomised controlled trials done in Nepal (2011-2014), Mali (2011-2014), and South Africa (2011-2013). Pregnant women, gestational age 17-34 weeks in Nepal, 28 weeks or more in Mali, and 20-36 weeks in South Africa, were enrolled. Women were randomly assigned 1:1 to a study group, in which they received trivalent inactivated influenza vaccine (IIV) in all three trials, or a control group, in which they received saline placebo in Nepal and South Africa or quadrivalent meningococcal conjugate vaccine in Mali. Enrolment at all sites was complete by April 24, 2013. Infants and women were assessed for respiratory illness, and samples from those that met the case definition were tested for influenza by PCR testing. Growth measurements, including length and weight, were obtained at birth at all sites, at 24 weeks in South Africa, and at 6 months in Nepal and Mali. The three trials are registered with ClinicalTrials.gov, numbers NCT01430689, NCT01034254, and NCT02465190. FINDINGS: 10 002 women and 9800 liveborn infants were included. Pooled efficacy of maternal vaccination to prevent infant PCR-confirmed influenza up to 6 months of age was 35% (95% CI 19 to 47). The pooled estimate was 56% (28 to 73) within the first 2 months of life, 39% (11 to 58) between 2 and 4 months, and 19% (-9 to 40) between 4 and 6 months. In women, from enrolment during pregnancy to the end of follow-up at 6 months postpartum, the vaccine was 50% (95% CI 32-63) efficacious against PCR-confirmed influenza. Efficacy was 42% (12 to 61) during pregnancy and 60% (36 to 75) postpartum. In women vaccinated before 29 weeks gestational age, the estimated efficacy was 30% (-2 to 52), and in women vaccinated at or after 29 weeks, efficacy was 71% (50 to 83). Efficacy was similar in infants born to mothers vaccinated before or after 29 weeks gestation (34% [95% CI 12 to 51] vs 35% [11 to 52]). There was no overall association between maternal vaccination and low birthweight, stillbirth, preterm birth, and small for gestational age. At 6 months of age, the intervention and control groups were similar in terms of underweight (weight-for-age), stunted (length-for-age), and wasted (weight-for-length). Median centile change from birth to 6 months of age was similar between the intervention and the control groups for both weight and length. INTERPRETATION: The assessment of efficacy for women vaccinated before 29 weeks gestational age might have been underpowered, because the point estimate suggests that there might be efficacy despite wide CIs. Estimates of efficacy against PCR-confirmed influenza and safety in terms of adverse birth outcomes should be incorporated into any further consideration of maternal influenza immunisation recommendations. FUNDING: Bill & Melinda Gates Foundation.

Experience and challenges on influenza and pertussis vaccination in pregnant women.

Young infants contribute to relatively high burden of vaccine-preventable diseases, including infections by influenza virus and Bordetella pertussis. Vaccination of pregnant women can enhance transplacental transfer of protective antibody to the fetus and protect the infant against disease during the first few months of life. Pregnant women are a priority group for seasonal influenza vaccination, due to third-trimester pregnancy being a risk-factor for severe influenza illness. Furthermore, randomized controlled trials confirmed that influenza vaccination during pregnancy confers protection against influenza-confirmed illness in the women, and their infants up to 3 months of age; and is also associated with 20% reduction in all-cause pneumonia among young-infants. Maternal influenza vaccination might also reduce the risk of low-birth weight, preterm births, and stillbirths however, data on this is conflicting. Vaccination of pregnant women with acellular pertussis vaccines reduces pertussis in their young infants by up to 93%. The increase in specific pertussis antibody among the infants born to vaccinated women might, however, interfere with the active pertussis vaccination of the infant following the primary series of vaccines. The clinical implication of this is yet to be ascertained, particularly since immune responses following the booster vaccine are unaffected. Vaccination of pregnant women with inactivated influenza vaccine and acellular pertussis vaccine have been demonstrated to confer protection to their young infants, and warrants consideration for inclusion into public health immunization programs, including in low and middle income countries.

The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates.

The global burden of disease caused by respiratory syncytial virus (RSV) is increasingly recognised, not only in infants, but also in older adults (aged ≥65 years). Advances in knowledge of the structural biology of the RSV surface fusion glycoprotein have revolutionised RSV vaccine development by providing a new target for preventive interventions. The RSV vaccine landscape has rapidly expanded to include 19 vaccine candidates and monoclonal antibodies (mAbs) in clinical trials, reflecting the urgency of reducing this global health problem and hence the prioritisation of RSV vaccine development. The candidates include mAbs and vaccines using four approaches: (1) particle-based, (2) live-attenuated or chimeric, (3) subunit, (4) vector-based. Late-phase RSV vaccine trial failures highlight gaps in knowledge regarding immunological protection and provide lessons for future development. In this Review, we highlight promising new approaches for RSV vaccine design and provide a comprehensive overview of RSV vaccine candidates and mAbs in clinical development to prevent one of the most common and severe infectious diseases in young children and older adults worldwide.

Review on the effects of influenza vaccination during pregnancy on preterm births.

Pregnant women are considered to be susceptible to severe influenza illness and are recommended as a priority group to be targeted for influenza vaccination in countries with vaccination programs. Increased rates of poor birth outcomes have also been temporally associated with influenza infection, especially when pandemics strains emerge. Even though the primary purpose for influenza vaccination during pregnancy is to decrease the risk of influenza infection in the women, other potential benefits include protection of their young infants against influenza illness and possibly improving birth outcomes. The 2009 influenza A/H1N1 pandemic highlighted the importance of influenza vaccination during pregnancy, after pregnant women were identified as a group with heightened morbidity and mortality during the pandemic. A few studies conducted before the 2009/10 season and a large number of reports during and after the 2009 pandemic have assessed the association between maternal influenza vaccination and birth outcomes. Although these studies indicate that influenza vaccination is safe for both the mother and the fetus, there are conflicting data on the effect of vaccination in improving preterm birth rates. We reviewed the 2 published randomized control trials and other observational studies that explored the relationship between maternal influenza vaccination and preterm births.

Effect of in-utero HIV exposure and antiretroviral treatment strategies on measles susceptibility and immunogenicity of measles vaccine.

INTRODUCTION: The high burden of maternal HIV-infection in sub-Saharan Africa may affect measles control. We evaluated the effect of in-utero HIV-exposure and antiretroviral treatment (ART) strategies on measles antibody kinetics prior and following measles vaccination. METHODS: Infants aged 6-12 weeks were enrolled. This included HIV-uninfected infants born to HIV-uninfected (HUU) and HIV-infected mothers (HEU). Additionally, we enrolled perinatal HIV-infected infants with CD4% equal or greater than 25% randomized to deferred-ART until clinically or immunologically indicated (Group-3) or immediate-ART initiation (Group-4). Group-4 was further randomized to interrupt ART at 1 year (Group-4a) or 2 years of age (Group-4b). Additionally, a convenience sample of HIV-infected infants with CD4⁺ less than 25% initiated on immediate-ART was enrolled (Group-5). Measles immunoglobulin-G antibodies were quantified by an indirect enzyme immunoassay with titers 330 mIU/ml or more considered 'sero-protective'. The referent group was HUU-children. RESULTS: The proportion with sero-protective titers at 7.3 weeks of age was higher in HUU (65.2%) compared with any HIV-infected group (range: 16.7-41.8%), but dropped to less than 17% in all groups at age 19.6 weeks. Twenty-eight weeks following the first measles vaccine, Group-4a was less likely to have sero-protective titers (79.3%) as compared to HUU (91.1%; P<0.0001), Group-3 (95.7%; P=0.003) or Group-4b (92.1%; P=0.018). Although the proportion with sero-protective levels were similar between groups immediately postbooster dose, this was lower in HEU (79.6%; P=0.002) and Group-4a (80.3%; P=0.010) compared with HUU (94.3%) 41-weeks later. CONCLUSION: Greater waning of immunity among HIV-infected children in whom ART was interrupted and in HEU following a booster-dose, indicate the possible need for further measles-booster doses after 2 years of age in these children.

Review on the immunogenicity and safety of PCV-13 in infants and toddlers.

Pneumococcal polysaccharide-protein conjugate vaccines (PCVs) generally protect against vaccine-serotype-specific pneumococcal disease. Additional serotypes included in the new 13-valent PCV (PCV-13) formulation and not in the first-generation 7-valent PCV (PCV-7) formulations are 1, 3, 5, 6A, 7F and 19A. Importantly, serotype 1 is associated with a high proportion and burden of pneumococcal disease in low-income countries, whilst serotype 19A emerged as the dominant disease-causing serotype following widespread PCV-7 immunization in the USA. In this article we present the available data on the immunogenicity and safety of PCV-13 in infants and children. Noninferiority studies indicate a similar immunogenicity profile between PCV-13 and PCV-7 recipients against most of the common serotypes. A favorable immunogenicity profile was also observed for at least five of the additional serotypes in PCV-13. An attenuated anamnestic response to serotype 3 was reported in five out of 14 studies. PCV-13 was demonstrated to have a similar acceptable safety profile to PCV-7 and no interference in immunogenicity of other concomitantly administered childhood vaccines was observed among PCV-13 recipients.