Welcome to the ISPPD 2022 Meeting Calendar

Background

Respiratory viruses predispose to infections caused by pneumococcus. Although this viral-pneumococcal synergism was first recognized during the 1918 influenza pandemic, most subsequent studies have focused on the effect of respiratory viruses on host pneumococcal immunity. The respiratory microbiome is a complementary and potentially modifiable mechanism by which respiratory viruses may promote pneumococcal colonization.

Methods

We conducted a longitudinal study of mother-infant pairs (n=266) in Gaborone, Botswana. We collected infant nasopharyngeal swabs every 1-2 months during the first year of life and tested these samples (n=1,901) for pneumococcus (lytA gene) and respiratory viruses (Table 1) by PCR. We used 16S ribosomal RNA gene sequencing to evaluate associations between respiratory virus infection and the relative abundances of bacterial genera within the nasopharyngeal microbiome.

Results

Pneumococcus was identified more frequently (68% vs. 43%; p<0.0001) and at higher colonization density (7.2 vs. 6.7 log copies/mL; p<0.0001) in samples with one or more respiratory viruses than in samples without respiratory viruses. In multivariable analyses, respiratory virus detection was associated with a 46% higher hazard of pneumococcal colonization (Cox proportional hazards model; HR: 1.46, 95% CI: 1.01-2.19). Respiratory virus infection was associated with losses of genera containing key bacterial commensals (Corynebacterium, Lactobacillus) and enrichment of the nasopharyngeal microbiome by Streptococcus and other genera containing common bacterial pathobionts (Figure 1).

Conclusions

Respiratory viruses contribute to population-level trends in pneumococcal colonization during infancy. Our data provide new insights into the dynamic interactions that exist between respiratory viruses, the nasopharyngeal microbiome, and pneumococcus within the upper respiratory tract.

Background

A trial has been conducted in children in Burkina Faso and Mali to investigate whether addition of azithromycin (AZ) to the antimalarials used for seasonal malaria chemoprevention reduces child mortality and hospital admissions. We report the sensitivity of nasal isolates of Streptococcus pneumoniae to AZ and other antibiotics obtained during the course of the trial.

Methods

AZ or placebo was administered monthly, in combination with the antimalarials sulphadoxine-pyrimethamine and amodiaquine, for four months over the annual malaria transmission seasons of 2014, 2015 and 2016. Nasopharyngeal swabs were collected from 2773 Burkinabe children and 2709 Malian children during seven surveys. Pneumococci were isolated and tested for sensitivity to AZ and other antibiotics.

Results

A total of 5482 nasopharyngeal samples were collected over 3 years. In Burkina Faso, the prevalence of overall carriage of Streptococcus pneumoniae decreased from 67.4% (290/430) in 2014 to 46.7% (185/396) in 2016. The proportion of AZ-resistant pneumococci in children who had received AZ increased from 4.9% (7/143) to 25.6% (22/86). In Mali, overall carriage increased from 63% (217/342) in 2014 to 40.5% (155/385) in 2016 with the proportion of AZ resistance of AZ resistance increasing from 7.6 (8/106) to 68.5% (37/54). Resistance remained high in Burkina Faso 17.7% (17/96) and Mali 19.1% (29/152) in the group of children who received AZ one year after the intervention was stopped.

Conclusions

Addition of AZ to the antimalarial combination was associated with an increase in resistance of pneumococci to AZ, which persisted for one year after the last administration of AZ.

Background

The contribution of pathogen genetic variation to the risk of developing lower

respiratory tract infection(LRTI) remains incompletely understood. We used genome

wide association study(GWAS) cohort to examine the contribution of genetic variations

to the risk of LRTI amongst African children enrolled in an intensively sampled birth

cohort.

Methods

Nasopharyngeal(NP) swabs were collected 2-weekly from 800 infants over the first year

of life. We analysed 393 and 777 pneumococcal genomes sampled from infants with

and without LRTI. We performed univariate linear mixed model GWAS(FaST-LMM) after

filtering out variants with missingness >5% and minor allele frequency(MAF) <1%.

Results

We identified 100,504 and 12,316,614 total SNPs and k-mers. Of these, 48,607 SNPs

and 389,918 unique k-mer patterns remained after quality control. GWAS analysis of

the pre-processed variants revealed statistically significant associationqs(- value<0.05)

in 17 SNPs and 3,237 k-mers (tagged by 64 unique k-mers) after Bonferroni correction.

Overall, 94%(16/17) SNPs and 84%(2,733/3,273 k-mers) were located in genic regions.

The variant-containing genes were diverse including surface-exposed,

transcription/response regulators and sugar/nutrient transporters.

Conclusions

Our preliminary analysis suggests that pathogen genetic variation may contribute to the

risk for LRTI but further analyses are required to elucidate the biological mechanisms

and degree of this contribution.

Background

In the first head-to-head trial conducted in a low-income country, 262 Papua New Guinean infants were randomized to receive PCV10 or PCV13 in a 1-2-3-month schedule. One and 6-month post-vaccination pneumococcal carriage rates remained high (≥ 87%), 20% of pneumococci being PCV10/PCV13-shared serotype and 10% PCV13-only. We now report pneumococcal carriage rates 20 months post-vaccination and antimicrobial susceptibility of pneumococci carried 1-20 months post-vaccination.

Methods

Nasopharyngeal swabs were cultured using standard bacteriological procedures. Antimicrobial susceptibility was determined by Kirby-Bauer disc diffusion and minimum inhibition concentrations.

Results

Overall pneumococcal carriage rates 20 months post-vaccination were comparable for PCV10 (93.6%, 86.6-97.6%) and PCV13 (88.6%, 80.1-94.4%) recipients, but PCV10/PCV13-shared serotypes carriage rates tended to be lower in PCV13 recipients (9.3%, 4.1-17.5%) than PCV10 recipients (19.8%, 12.2-29.5%), as was carriage of PCV13-only serotypes (PCV13: 4.7%, 1.3-11.5%) (PCV10: 12.1%, 6.2-20.6%). Of the pneumococci carried in either vaccine group 1-, 6- and 20-months post-vaccination, 42.0%, 46.7%, and 45.9% were non-susceptible to penicillin, and 39.2%, 43.9%, and 37.2% non-susceptible to trimethoprim-sulfamethoxazole (TMP/SXT), respectively. PCV serotypes 19A, 19F, and 23F were in the top 5 most-commonly carried pneumococci (4.1%, 4.1%, and 5.6%, respectively), and were associated with high non-susceptibility to penicillin (19A, 70%; 19F, 75%) and/or TMP/SXT (19A, 80%; 19F, 50%; 23F, 61%).

Conclusions

Pneumococcal carriage rates remain high in PNG children, even after PCV vaccination, due to the broad range of carriage serotypes (71 serotypes) and limited effect of PCVs on carriage. Serotype-independent vaccines are needed to reduce the burden of pneumococcal disease in such settings.

Background

Colonisation of human nasopharynx with pneumococcus is the main reservoir of transmission and disease. Using a human exposure model, we previously demonstrated that hands can be vehicles of pneumococcal transmission, leading to acquisition of colonisation. Here, we used an experimental human pneumococcal challenge (EHPC) model to investigate pneumococcal shedding and the role of bacterial density and viral co-infection in shedding and transmission.

Methods

Healthy adults (aged 18-50 years) were inoculated with serotype 6B. Pneumococcal colonisation status and density were assessed in nasal wash samples collected pre- and at several time points after inoculation (D2, D6, D16, D22). Pneumococcal shedding was assessed in a) cough samples, b) facemasks and c) nose-to-hand swab samples at the same time points.

Results

Amongst the colonised subjects, 22.7% (17/75) shed pneumococcus at any time point, with 16% (12/75) of them expiring bacteria from the nose to their hand and 6.7% (5/75) from the mouth while coughing. Only 1 out of the 17 shedders expired bacteria from both nasal and oral route. Volunteers colonised with densities <10² CFU/ml of NW were identified as non-shedders, whereas shedding rates were linearly increased at density levels from 10³ to 10⁶ CFU/ml NW. Asymptomatic viral infection promoted pneumococcal shedding.

Conclusions

In this study, we described for the first time pneumococcal shedding in healthy colonised adults, who can also serve as a reservoir of transmission, and we demonstrated that density of colonisation is a major factor for bacterial shedding.

Background

Despite widespread use of pneumococcal conjugate vaccines, particularly in children, an important burden of pneumococcal disease remains in older adults. 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 aged ≥60 years and no individuals under the age of 60 lived in the household. Saliva samples and questionnaires were obtained every 2 weeks for a period of 10 weeks (six time-points total). Following culture-enrichment, extracted DNA was tested using qPCR for pneumococcus-specific sequences piaB and lytA. Individuals were considered positive when Ct-values for piaB were <40.

Results

We collected 567 saliva samples from 95 individuals (48 household pairs). Of those, 9.2% samples tested positive for pneumococcus, representing 28/95 (29%) individuals and 20/48 (43%) households. Ten (68%) carriers tested positive at multiple time-points, with two (7%) individuals colonized at all six time-points. For five households, both members were identified as carriers at either the same time-point or on consecutive time-points. Individuals who had regular contact with school-aged children had higher carriage prevalence (17%). There were instances where both household members were colonized and did not report contact with children, but the numbers were too small to formally evaluate the rate of within-household transmission.

Conclusions

We found that 29% of older adults carried pneumococcus during the 10-week study period. While prevalence was particularly high among those who had contact with school-aged children, carriage was not limited to this group.

Background

Bajau tribe known as ‘Sea Nomads’ was originated from Malay Peninsula of Southeast Asia. Wakatobi, Indonesia, hosts several of Bajau settlements where the tribe inhabited the coast and build semi-permanent houses overwater. Remote settlements and supernatural believes are among the factors to lack of access to health care in this tribe. The people commonly live in crowded house with impoverished living conditions and poor hygiene. Extremely limited data available on pneumococcal carriage and serotype distribution in Sea Nomads population.

Methods

We enrolled children <5 years old in the settlements of Bajau Tribe (Sea Nomads Tribe) located in Wakatobi Islands, Indonesia from October 2018 to February 2019. Nasopharyngeal (NP) swabs were evaluated for colonization of S. pneumoniae using molecular method, serotyping with multiplex-PCR and antimicrobial susceptibility test with disc-diffusion. Logistic regression was performed for potential risk factors analysis.

Results

We collected 499 NP swabs. 61.1% were colonized with S. pneumoniae. 47.6% of the isolates were PCV13-type. Serotype 6A/B, 23F and 19F were the most common with 17.5%, 13.8% and 8.7%, respectively. Multi-drug resistance S. pneumoniae was 40.4%. Cigarette smoke and rhinorrhea were significant risk factors to colonization with OR 1.6 (1.1 – 2.3) and 2.1 (1.4 – 3.3), respectively. Firewood has higher risk to colonization compare to LPG/Gas with OR 4.0 (1.2 - 13.5).

Conclusions

S. pneumoniae resistance was observed to commonly used antibiotics. Most of the isolates were vaccine-type. This result may contribute to evidence-based for decision making policy on vaccination and antibiotics use in Indonesia.

Background

Streptococcus pneumoniae (pneumococcus), is an opportunistic pathogen that commonly colonizes the upper airway asymptomatically. It is responsible for life-threatening invasive pneumococcal disease (IPD) around the world. Nasopharyngeal microbiome (NPM) can be one of the important factors which influence the penetration to host tissues and progression of IPD. Differences in the NPM in colonized pneumococcus (CP) and IPD may unveil the key factors in development of IPD as CP can progress in IPD.

Methods

NPM (V4-region of 16S-rRNA genes sequenced via next-generation sequencing) from the children corresponding to two groups (CP and IPD) were collected from recent studies. Phylogenetic analysis, taxonomic annotation, diversity analysis and differential abundance of taxa were conducted through FastTree, q2-feature-classifier, q2-diversity module in QIIME2 and LEfSe respectively.

Results

High Faith’s phylogenetic-diversity and low Pielou’s evenness were observed in IPD-group (p-value<0.001) that may be the pattern in NPM which favors the IPD progression (Figure-1A-B). Significant difference was also observed in the permutational multivariate analysis of variance (PERMANOVA) between the groups (Figure-1). Finally, 30 differentially abundant taxa between the groups were identified (Figure-1). High abundance of streptococcus ovis and Streptococcus equi was found in IPD which may favor the IPD development. Similarly, Salmonella Infantis and Streptococcus salivarius were found in CP which may suppress the development of IPD (Figure-1J-K).

Conclusions

Patterns in microbiome diversity and abundance of species that may favor/suppress the IPD were observed. Importantly, confounding factors such as diverse populations and age groups were present in the study and further studies may be required to confirm the findings.