Association of pneumococcal carriage in infants with the risk of carriage among their contacts in Nha Trang, Vietnam: A nested cross-sectional survey.

BACKGROUND: Infants are at highest risk of pneumococcal disease. Their added protection through herd effects is a key part in the considerations on optimal pneumococcal vaccination strategies. Yet, little is currently known about the main transmission pathways to this vulnerable age group. Hence, this study investigates pneumococcal transmission routes to infants in the coastal city of Nha Trang, Vietnam. METHODS AND FINDINGS: In October 2018, we conducted a nested cross-sectional contact and pneumococcal carriage survey in randomly selected 4- to 11-month-old infants across all 27 communes of Nha Trang. Bayesian logistic regression models were used to estimate age specific carriage prevalence in the population, a proxy for the probability that a contact of a given age could lead to pneumococcal exposure for the infant. We used another Bayesian logistic regression model to estimate the correlation between infant carriage and the probability that at least one of their reported contacts carried pneumococci, controlling for age and locality. In total, 1,583 infants between 4 and 13 months old participated, with 7,428 contacts reported. Few infants (5%, or 86 infants) attended day care, and carriage prevalence was 22% (353 infants). Most infants (61%, or 966 infants) had less than a 25% probability to have had close contact with a pneumococcal carrier on the surveyed day. Pneumococcal infection risk and contact behaviour were highly correlated: If adjusted for age and locality, the odds of an infant's carriage increased by 22% (95% confidence interval (CI): 15 to 29) per 10 percentage points increase in the probability to have had close contact with at least 1 pneumococcal carrier. Moreover, 2- to 6-year-old children contributed 51% (95% CI: 39 to 63) to the total direct pneumococcal exposure risks to infants in this setting. The main limitation of this study is that exposure risk was assessed indirectly by the age-dependent propensity for carriage of a contact and not by assessing carriage of such contacts directly. CONCLUSIONS: In this study, we observed that cross-sectional contact and infection studies could help identify pneumococcal transmission routes and that preschool-age children may be the largest reservoir for pneumococcal transmission to infants in Nha Trang, Vietnam.

Sero and Carriage Epidemiology of Pertussis in Urban and Rural Regions in Vietnam.

The underestimation of the pertussis burden prompted our study to investigate the prevalence of recent pertussis infection, its associated factors, and antibody titer changes in the same individuals in Vietnam. Two cross-sectional surveys were conducted in Nha Trang in 2017 and Quang Ngai in 2019, representing high- and low-vaccine-coverage areas, respectively. Serum anti-pertussis toxin immunoglobulin-G (anti-PT IgG) ≥ 62.5 IU/mL by ELISA indicated infection in the previous 12 months. In Nha Trang, the participants of the 2017 survey were followed up in 2019. Logistic regression was used to determine the odds ratios for the characteristics associated with anti-PT IgG ≥ 62.5. The age-stratified prevalence in patients aged >2 years ranged from 2.1% (age 26-35) to 9.6% (3-5) in Nha Trang (2017) and from 7.2% (age 26-35) to 11.4% (6-15) in Quang Ngai. The prevalence tended to be higher in Quang Ngai across all age groups. Cough, recent antibiotic use, and smoking in Nha Trang were positively associated with an anti-PT IgG of ≥62.5, and having been diagnosed with pertussis and persistent cough with paroxysms/whoop in Quang Ngai were positively associated with an anti-PT IgG of ≥62.5. No nasopharyngeal swabs were positive for Bordetella pertussis using real-time PCR. The geometric mean of the IgG titer ratio from 2019 to 2017 was 1.45 in the paired samples. This study emphasizes Bordetella pertussis circulation across all age groups in both low- and high-vaccine-coverage settings in Vietnam, underscoring the need for continuous and standardized surveillance for a comprehensive understanding of its epidemiology.

The seroprevalence, waning rate, and protective duration of anti-diphtheria toxoid IgG antibody in Nha Trang, Vietnam.

BACKGROUND: Diphtheria cases reported in Central Vietnam since 2013 were mainly in children aged 6-15 years, which may reflect an immunity gap. There is little information on population immunity against diphtheria in countries without a school-entry booster dose. We aimed to measure the age-stratified seroprevalence of anti-diphtheria toxoid antibodies, quantify the change in antibody levels in individuals over time, and estimate the length of protective immunity after vaccination in well-vaccinated communities in Vietnam. METHODS: An age-stratified seroprevalence survey among individuals aged 0-55 years was conducted at Nha Trang, Vietnam. The same participants were followed up after two years to quantify the change in antibody levels. IgG was measured using ELISA. The length of protective immunity after vaccination was estimated using a mixed-effect linear regression model with random intercept. RESULTS: Overall seroprevalence was 26% (95%CI:20-32%). Age-stratified seroprevalence was 68% (95%CI:4-11%), 7% (95%CI:4-11%), 12% (95%CI:7-19%), 33% (95%CI:27-40%), and 28% (95%CI:17-43%) among those aged ≤5, 6-15,16-25, 26-35, and 36-55 years, respectively. The antibody levels declined by 47% (95%CI:31-59%) over two years, and the predicted duration of vaccine-derived protective immunity after receiving four doses was 4.3 years (95%CI:3.5-5.3) among participants aged six years or younger. CONCLUSION: Given the low seroprevalence and short period of vaccine protection, a school-entry booster dose (5-7 years) is recommended in Vietnam.

Effect of pneumococcal conjugate vaccine on prevalence of otitis media with effusion among children in Vietnam.

PURPOSE: Otitis media with effusion (OME) is common in young children and is associated with Streptococcus pneumoniae infection. We aimed to determine the impact of pneumococcal conjugate vaccine (PCV) introduction on the prevalence of OME and OME associated with vaccine-type (VT) or non-VT. METHODS: Population-based cross-sectional surveys were conducted in pre- (2016) and post-PCV periods (2017, 2018, and 2019) at selected communes in Nha Trang, Vietnam. For each survey, we randomly selected 60 children aged 4-11 months and 60 aged 14-23 months from each commune. Nasopharyngeal sample collection and tympanic membrane examination by digital otoscope were performed. S. pneumoniae was detected and serotyped by lytA qPCR and microarray. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using Firth's logistic regression, stratified by age group. RESULTS: Over the four surveys, 2089 children had a bilateral ear examination. Compared to pre-PCV, the prevalence of OME reduced in 2018 (OR 0.51, 95 %CI 0.28-0.93) and in 2019 (OR 0.53, 95 %CI 0.29-0.97) among the <12-month-olds, but no significant reduction among the 12-23-month-olds. The prevalence of OME associated with VT pneumococcus decreased in 2018 and 2019 (2018: OR 0.14, 95 %CI 0.03-0.55; 2019: OR 0.20, 95 %CI 0.05-0.69 in the <12-months-olds, 2018: OR 0.05, 95 %CI 0.00-0.44, 2019: OR 0.41, 95 %CI 0.10-1.61 in the 12-23-months-olds). The prevalence of OME associated with non-VT pneumococcus increased in the 12-23-month-olds in 2017 (OR 3.09, 95 %CI 1.47-7.45) and returned to the pre-PCV level of prevalence in 2018 and 2019 (OR 0.94, 95 %CI 0.40-2.43 and 1.40, 95 %CI 0.63-3.49). CONCLUSION: PCV10 introduction was associated with a reduction of OME prevalence in infants but not in older children.

Prevalence of Streptococcus pneumoniae in conjunctival flora and association with nasopharyngeal carriage among children in a Vietnamese community.

Conjunctival pneumococcal serotypes among members of a community have not been investigated well. We determined the prevalence and association of Streptococcus pneumoniae in the nasopharynx and conjunctiva among children in a community before pneumococcal conjugate vaccine introduction. In October 2016, conjunctival and nasopharyngeal swabs were collected from children (< 24 months old) and nasopharyngeal swabs from mothers in Nha Trang, Vietnam. Quantitative lytA PCR and DNA microarray were performed to detect and serotype S. pneumoniae. The association between S. pneumoniae in the nasopharynx and conjunctiva was evaluated using multivariable logistic regression model. Among 698 children, 62 (8.9%, 95% CI 6.9-11.2%) were positive for S. pneumoniae in the conjunctiva. Non-encapsulated S. pneumoniae were most commonly identified, followed by serotypes 6A, 6B, and 14. Nasopharyngeal and conjunctival detection were positively associated (aOR 47.30, 95% CI 24.07-92.97). Low birth-weight, day-care attendance, and recent eye symptoms were independently associated with S. pneumoniae detection in the conjunctiva (aOR 11.14, 95% CI 3.76-32.98, aOR 2.19, 95% CI 1.45-3.31, and aOR 3.59, 95% CI 2.21-5.84, respectively). Serotypes and genotypes in the conjunctiva and nasopharynx matched in 87% of the children. Three mothers' nasopharyngeal pneumococcal samples had matched serotype and genotype with their child's in the conjunctiva and nasopharynx. S. pneumoniae presence in nasopharynx and conjunctiva were strongly associated. The high concordance of serotypes suggests nasopharyngeal carriage may be a source of transmission to the conjunctiva.