Infant Pneumococcal Carriage in Belgium Not Affected by COVID-19 Containment Measures

Streptococcus pneumoniae is an important and frequently carried respiratory pathogen that has the potential to cause serious invasive diseases, such as pneumonia, meningitis, and sepsis. Young children and older adults are among the most vulnerable to developing serious disease. With the arrival of the COVID-19 pandemic and the concomitant restrictive measures, invasive disease cases caused by respiratory bacterial species, including pneumococci, decreased substantially. Notably, the stringency of the containment measures as well as the visible reduction in the movement of people appeared to coincide with the drop in invasive disease cases. One could argue that wearing protective masks and adhering to social distancing guidelines to halt the spread of the SARS-CoV-2 virus, also led to a reduction in the person-to-person transmission of respiratory bacterial species. Although plausible, this conjecture is challenged by novel data obtained from our nasopharyngeal carriage study which is performed yearly in healthy daycare center attending children. A sustained and high pneumococcal carriage rate was observed amid periods of stringent restrictive measures. This finding prompts us to revisit the connection between nasopharyngeal colonization and invasion and invites us to look closer at the nasopharyngeal microbiome as a whole.

Epidemiology of Streptococcus pneumoniae serotypes in children before and after pneumococcal vaccination

Aim. To investigate how the pneumococcal vaccination affects the distribution of Streptococcus pneumoniae serotypes.Materials and Methods. In 2011-2019, 1,852 healthy children (1,354 aged ≤ 5 years and 480 aged from 6 to 17 years) were examined for the nasopharyngeal pneumococcal carriage. Of them, 539 children were tested before the start of pneumococcal vaccination (2011-2014), while 1,313 were tested during the vaccine campaign (2015-2019). Pneumococcal strains were serotyped using multiplex polymerase chain reaction.Results. Streptococcus pneumoniae serotype distribution considerably differed between children ≤ 5 and 6-17 years of age. Serotypes 23F, 19F, 19A, 6AB, and 15BC were prevalent in children ≤ 5 years of age while the older children were characterised by a high prevalence of capsular serotypes (3 and 33AF/37), serogroup 9 (9AV and 9LN), non-typeable streptococci, as well as 19F, 6AB and 6CD serotypes. Vaccination was associated with a significantly decreased prevalence of Streptococcus pneumoniae carriage (from 41.5% to 19.2%) among children ≤ 5 years of age, while this reduction was less pronounced (from 13.5 to 9.0%) in older children. Vaccination led to the shift in the distribution of pneumococcal serotypes towards an increased prevalence of non-vaccine serotypes that was particularly prominent in children ≤ 5 years of age. In particular, vaccination reduced the prevalence of 23F and 19A pneumococcal serotypes but heightened prevalence of 11AD serotype and to the appearance of previously undetected serotypes such as 8, 10A, 17F, 22F, 24ABF, 34, and 39.Conclusion. Pneumococcal vaccination decreased prevalence of pneumococcal carriage, yet causing a serotype replacement effect requiring improved microbiological monitoring in children of all age groups.

Estimating the contribution of HIV-infected adults to household pneumococcal transmission in South Africa, 2016–2018: A hidden Markov modelling study

Human immunodeficiency virus (HIV) infected adults are at a higher risk of pneumococcal colonisation and disease, even while receiving antiretroviral therapy (ART). To help evaluate potential indirect effects of vaccination of HIV-infected adults, we assessed whether HIV-infected adults disproportionately contribute to household transmission of pneumococci. We constructed a hidden Markov model to capture the dynamics of pneumococcal carriage acquisition and clearance observed during a longitudinal household-based nasopharyngeal swabbing study, while accounting for sample misclassifications. Households were followed-up twice weekly for approximately 10 months each year during a three-year study period for nasopharyngeal carriage detection via real-time PCR. We estimated the effect of participant’s age, HIV status, presence of a HIV-infected adult within the household and other covariates on pneumococcal acquisition and clearance probabilities. Of 1,684 individuals enrolled, 279 (16.6%) were younger children (<5 years-old) of whom 4 (1.5%) were HIV-infected and 726 (43.1%) were adults (≥18 years-old) of whom 214 (30.4%) were HIV-infected, most (173, 81.2%) with high CD4+ count. The observed range of pneumococcal carriage prevalence across visits was substantially higher in younger children (56.9–80.5%) than older children (5–17 years-old) (31.7–50.0%) or adults (11.5–23.5%). We estimate that 14.4% (95% Confidence Interval [CI]: 13.7–15.0) of pneumococcal-negative swabs were false negatives. Daily carriage acquisition probabilities among HIV-uninfected younger children were similar in households with and without HIV-infected adults (hazard ratio: 0.95, 95%CI: 0.91–1.01). Longer average carriage duration (11.4 days, 95%CI: 10.2–12.8 vs 6.0 days, 95%CI: 5.6–6.3) and higher median carriage density (622 genome equivalents per millilitre, 95%CI: 507–714 vs 389, 95%CI: 311.1–435.5) were estimated in HIV-infected vs HIV-uninfected adults. The use of ART and antibiotics substantially reduced carriage duration in all age groups, and acquisition rates increased with household size. Although South African HIV-infected adults on ART have longer carriage duration and density than their HIV-uninfected counterparts, they show similar patterns of pneumococcal acquisition and onward transmission.

A Cluster-randomised, Non-inferiority Trial of the Impact of a Two-dose Compared to Three-dose Schedule of Pneumococcal Conjugate Vaccination in Rural Gambia: the PVS Trial

Background:Pneumococcal conjugate vaccines (PCV) effectively prevent pneumococcal disease but the global impact of pneumococcal vaccination is hampered by the cost of PCV. The relevance and feasibility of trials of reduced dose schedules is greatest in middle- and low-income countries, such as The Gambia, where PCV has been introduced with good disease control but where transmission of vaccine-type pneumococci persists. We are conducting a large cluster-randomised, non-inferiority, field trial of an alternative reduced dose schedule of PCV compared to the standard schedule, the PVS trial.Methods:PVS is prospective, cluster-randomised, non-inferiority, real-world field trial of an alternative schedule of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months (i.e. the alternative ‘1+1’ schedule) compared to the standard schedule of three primary doses scheduled at 6, 10, and 14 weeks weeks of age (i.e. the stardard ‘3+0’ schedule). The intervention will be delivered for 4 years. The primary endpoint is the population-level prevalence of nasopharyngeal vaccine-type pneumococcal carriage in children aged 2 weeks to 59 months with clinical pneumonia in Year 4 of the trial. Participants and field staff are not masked to group allocation while measurement of the laboratory endpoint will be masked. Sixty-eight geographic population clusters have been randomly allocated, in a 1:1 ratio, to each schedule and all resident infants are eligible for enrolment. All resident children less than 5 years of age are under continuous surveillance for clinical safety endpoints measured at 11 health facilities; invasive pneumococcal disease, radiological pneumonia, clinical pneumonia, and hospitalisations. Secondary endpoints include the population-level prevalence of nasopharyngeal vaccine-type pneumococcal carriage in Year 2 and 4 and vaccine-type carriage prevalence in unimmunised infants aged 6-12 weeks in Year 4. The trial includes components of mathematical modeling, health economics, and health systems research.Discussion:Analysis will account for potential non-independence of measurements by cluster, comparing the population-level impact of the two schedules with interpretation at the individual level. The non-inferiority margin is informed by the ‘acceptable loss of effect’ of the alternative compared to standard schedule. The secondary endpoints will provide substantial evidence to support the interpretation of the primary endpoint. PVS will evaluate the effect of transition from a standard 3+0 schedule to an alternative 1+1 schedule in a setting of high pneumococcal transmission. The results of PVS will inform global decision-making concerning the use of reduced-dose PCV schedules.Trial registration: International Standard Randomised Controlled Trial Number – 15056916.

Molecular surveillance of pneumococcal carriage following completion of immunization with the 13-valent pneumococcal conjugate vaccine administered in a 3 + 1 schedule

In a cross-sectional study, with the use of molecular methods, we aimed to gain insight into oropharyngeal pneumococcal colonization over time in 1212 Greek children recruited in general pediatric settings throughout the country; they were fully vaccinated with PCV13 (3 + 1 schedule). A single sample was obtained from each child at a time interval of 26 days to 70 months after administration of the 4th (booster) PCV13 dose; sampling time was divided into six time intervals. Carriage of Streptococcus pneumoniae was detected by real-time PCR targeting the lytA gene and isolates were serotyped by singleplex real-time PCR assays. Multiple control procedures to avoid false-positive results were applied. We showed an overall S. pneumoniae carriage rate of 48.6%. Serotyping identified typeable isolates in 82% of the total lytA-positive samples. Non-PCV13 serotypes represented 83.8% of total isolates when excluding serogroups with mixed PCV13 and non-PCV13 serotypes. In multivariate analysis daycare/school attendance emerged as the main contributing factor. Notably, serotypes 19A and 3 were the only two PCV13 serotypes the colonization rate of which increased over time (χ2 for trend P < 0.001 and P = 0.012, respectively). The application of the SP2020 gene on lytA-positive serotyped samples showed pneumococcal colonization in 97% of cases, and the overall colonization profile over time closely resembled that of the lytA gene. With the provisions of the methodological approach and age group of our study, the use of the oropharynx emerges as a reliable alternative to the nasopharynx in estimating pneumococcal carriage in epidemiological studies.

Prevalence of Pneumococcal Carriage among Jordanian Infants in the First 6 Months of Age, 2008–2016

Background: Streptococcus pneumoniae is an opportunistic human-adapted pathogen driven by nasopharyngeal carriage. Aims: To find the pneumococcal carriage rate, resistance, serotypes, and coverage of pneumococcal conjugate vaccines (PCVs) among infants in the first six months of age in the period from March 2008 to April 2016. Methods: Nasopharyngeal swabs (NP) were taken from healthy infants from the northern part of Jordan. Swabs were processed for cultivation, identification, resistance testing and serotyping according to standard methods. Results: During the surveillance period, 484 infants of this age group were tested, with a total carriage rate of 56.2%. 96.2% of infants one to two months of age got one PCV7 injection and were 58% carriers at the time of the first injection. At age three to four months, 84.9% had received two injections, with a carriage rate of 54.9% at the time of the second injection. At ages five to six months, 12.5% had received one to three injections, with a carriage rate of 43.8%. Predominant serotypes in all age groups were 19F (12.5%), 6A (11.4%), 11A (8.4%), 19A (7.0%), 6B (6.6%), 23F (5.9%), 15B (5.1%), 15A and 23A (4.0% each). Coverage of PCV7, PCV13 and the future PCV20 among all cases were 30.5%, 50.7% and 70.6%, respectively. The highest coverage rate of 78.6% was noticed in the age group at five to six months with the future PCV20. Antibiotic resistance was the highest in the first age group. Conclusions: Pneumococcal carriage starts from the first month of the infant’s life. The highest coverage was noticed for PCV20, which implies the necessity for inoculation with future vaccines.

1321. Acquisition and Transmission of Streptococcus pneumoniae in Individuals Over the Age of 60 Years Residing in New Haven, CT, USA

Background Despite the widespread use of pneumococcal conjugate vaccines, particularly in children, an important burden of pneumococcal disease remains in older adults. The acquisition and transmission rates of pneumococcus between older adults have not been well characterized. Methods Between October 2020-June 2021, couples living in the Greater New Haven Area were enrolled if both individuals were over the age of 60 years and did not have any individuals under the age of 60 years living in the household. Saliva samples and questionnaires regarding social patterns and medical history were obtained every 2 weeks for a period of 10 weeks. Following culture-enrichment, extracted DNA was tested using qPCR for pneumococcus-specific sequences piaB and lytA. Individuals were considered positive for pneumococcal carriage when qPCR Ct-values for piaB +/- lytA were less than 40. Results To date, we have collected 495 saliva samples from 95 individuals (48 households). Of 495 saliva samples, 31 (5.9%) have tested positive for pneumococcus by either piaB only (n=9) or both lytA and piaB (n=22). Of 95 individuals, 16 (16.8%) (representing 13, or 27.1% households) have tested positive at least once. Six of the 16 (37.5%) carriers tested positive at multiple timepoints, though none were colonized at all 6 time points over the course of the 10 weeks of study enrolment. For 3 of the 48 (6.3%) households, both members of the couple were identified as carriers, though not necessarily at the same sampling moment. Conclusion The preliminary findings of this longitudinal transmission model demonstrate evidence of pneumococcal acquisition among older adults measured by molecular tools. These transmission patterns and high rates of pneumococcal carriage in adults were observed during a period when the COVID-19 pandemic led to numerous preventative public health measures that may have reduced pneumococcal transmission (e.g., social distancing, mask wearing, bans on mass gatherings, restaurant closures, travel restrictions). Disclosures Anne Wyllie, PhD, Global Diagnostic Systems (Consultant)Pfizer (Advisor or Review Panel member, Research Grant or Support)PPS Health (Consultant)Tempus Labs, Inc (Research Grant or Support) Ronika Alexander-Parrish, RN, MAEd, Pfizer (Employee, Shareholder) Adriano Arguedas, MD, Pfizer (Employee) Bradford D. Gessner, MD, MPH, Pfizer Inc. (Employee) Daniel Weinberger, PhD, Affinivax (Consultant)Merck (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support)

Pneumococcal carriage and antibiotic susceptibility patterns in mother-baby pairs in a rural community in Eastern Uganda: a cross-sectional study

Background: Pneumococcal carriage predisposes children to pneumonia. Pneumonia poses a significant threat to the lives of children below five years old worldwide, contributing to a high number of hospitalizations and death. Morbidity and morbidity are especially common in children under five and the elderly, although any age group can be affected. This study aimed to estimate pneumococcal carriage and determine antibiotic susceptibility patterns of the pneumococci isolated from mother-baby pairs in Ngora district after the rollout of the pneumococcal vaccine. We hypothesized that high carriage of Streptococcus pneumoniae in mothers leads to carriage in their babies and hence a greater chance of contracting pneumonia. Methods: Consecutive sampling was used to select 152 mother-baby pairs from community visits and those seeking care at the health facility. We collected nasal swabs from both baby and mother for culture and sensitivity testing using Kirby-Bauer’s agar disc diffusion method. Data was also collected from the mothers who consented to take part in the study, using an interviewer-administered questionnaire. Results: This study found that there was a low prevalence of pneumococcal carriage in the mother-baby pair in the Ngora district. Only one mother-baby pair (1/152) was found to be colonized with pneumococci in both mother and baby and the rest of S. pneumoniae colonized either the mother or baby. We also observed high rates of microbial resistance to penicillin, which is the first-line drug for the management of pneumonia in Uganda. Also, high resistance patterns were recorded with chloramphenicol (50%) and tetracycline (50%), whereas the lowest resistance was recorded in clindamycin (17%). Conclusions: The relationship between pneumococcal carriage and immunization status suggests that the pneumococcal vaccine is protective against the pneumococcal carriage. Resistance of S. pneumoniae to commonly used antibiotics was high.

Pneumococcal carriage and antibiotic susceptibility patterns in mother-baby pairs in a rural community in Eastern Uganda: a cross-sectional study

Background: Pneumococcal carriage predisposes children to pneumonia. Pneumonia poses a significant threat to the lives of children below five years old worldwide, contributing to a high number of hospitalizations and death. Morbidity and morbidity are especially common in children under five and the elderly, although any age group can be affected. This study aimed to estimate pneumococcal carriage and determine antibiotic susceptibility patterns of the pneumococci isolated from mother-baby pairs in Ngora district after the rollout of the pneumococcal vaccine. We hypothesized that high carriage of Streptococcus pneumoniae in mothers leads to carriage in their babies and hence a greater chance of contracting pneumonia. Methods: Consecutive sampling was used to select 152 mother-baby pairs from community visits and those seeking care at the health facility. We collected nasal swabs from both baby and mother for culture and sensitivity testing using Kirby-Bauer’s agar disc diffusion method. Results: This study found that there was a low prevalence of pneumococcal carriage in the mother-baby pair in the Ngora district. We also observed high rates of microbial resistance to penicillin, which is the first-line drug for the management of pneumonia in Uganda. Conclusions: The relationship between pneumococcal carriage and immunization status suggests that the pneumococcal vaccine is protective against the pneumococcal carriage. Resistance of S. pneumoniae to commonly used antibiotics was high.