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Non-Vaccine Serotype Replacement and Subdominant Persistence of Vaccine Types in Nepalese Infants Following PCV10
Fleurette Mbuyakala Domai1,2,3, Dhruba Shrestha4, Raj Kumar Shrestha4
1Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan.
Insights
The 10-valent pneumococcal conjugate vaccine (PCV10) reduced vaccine-type pneumococcal carriage in Nepalese infants, but non-vaccine serotypes (NVTs) increased, highlighting the need for broader protection strategies.
Area of Science:
- Pediatric Infectious Diseases
- Vaccinology
- Microbiology
Background:
- Streptococcus pneumoniae causes significant child mortality in Nepal.
- The 10-valent pneumococcal conjugate vaccine (PCV10) has been introduced, but its effectiveness is challenged by non-vaccine serotypes (NVTs) and undetected multiple serotype carriage.
- Understanding serotype distribution changes post-PCV10 is crucial for public health strategies.
Purpose of the Study:
- To investigate changes in pneumococcal serotype distribution in Nepalese infants before and after PCV10 immunization.
- To identify dominant serotypes in the post-vaccine era.
- To analyze risk factors associated with pneumococcal carriage.
Main Methods:
- A longitudinal cohort study was conducted in Bhaktapur, Nepal (2020-2022).
- Nasopharyngeal swabs were collected from infants at 6 weeks, 9 months, and 12 months.
- A nanofluidic qPCR platform was used to detect multiple serotypes and quantify bacterial load, with Inverse Probability Weighting (IPW) for risk factor analysis.
Main Results:
- PCV10 significantly reduced vaccine-type (VT) carriage from 32.8% to 4.8%.
- NVTs rapidly increased and became dominant, with serotypes 35B, 19A, 6C/6D, and 15B/15C emerging as most common.
- Risk factors for carriage included older infancy, household kitchen proximity, and winter/pre-monsoon seasons.
Conclusions:
- PCV10 effectively reduced VT pneumococcal circulation but created space for NVTs.
- Persistent VT carriage in subdominant niches poses a risk for re-emergence and antibiotic resistance.
- Higher-valent vaccines and environmental interventions are needed for sustained pneumococcal reduction.
Abstract:
Background:Streptococcus pneumoniae is a leading cause of child mortality in Nepal despite the introduction of the 10-valent pneumococcal conjugate vaccine (PCV10). Vaccine effectiveness is threatened by the emergence of non-vaccine serotypes (NVTs) and the multiple serotypes carriage which often fail to be detected by traditional methods. We aimed to study changes in serotype distribution before and after PCV10 immunization among infants, including serotype dominance in Nepalese infants in the post-vaccine era. Methods: We enrolled infants in a longitudinal cohort study (2020-2022) conducted in Bhaktapur, Nepal. Nasopharyngeal swabs were collected before PCV10 dose 1 (6 weeks) and at 9 and 12 months post-immunization. We used a sensitive nanofluidic qPCR platform to detect multiple serotypes and establish their hierarchy by quantifying the bacterial load of each strain. Inverse Probability Weighting (IPW) adjusted risk factor analysis was used to account for loss to follow-up. Results: PCV10 successfully reduced vaccine-type (VT) carriage, declining sharply from 32.8% at 6 weeks to 4.8% at 12 months. VTs were pushed from being the dominant strain to occupying subdominant roles in co-colonization. Conversely, NVTs rapidly filled the vacated niche, showing a significant increase in their dominant status (p < 0.001). The most common replacing NVTs that rose to dominance were 35B, 19A, 6C/6D, and 15B/15C. Significant risk factors for carriage included older infancy (aOR 3.4, 95%CI: 2.6-4.5 at 9 months), a household kitchen in the living area (aOR 1.4, 95%CI: 1.0-1.9), and winter (aOR 1.7, 95%CI: 1.5-2.7) and pre-monsoon seasons (aOR 2.0, 95%CI: 1.5-2.8). Conclusions: While PCV10 reduced overall VT circulation, the persistence of VTs in subdominant niches creates a continuous reservoir for potential re-emergence and antibiotic resistance. This clear hierarchical shift in dominance towards NVTs underscores the urgent need for a public health strategy that includes the adoption of a higher-valent PCV to provide broader protection, and interventions targeting environmental risk factors are essential to sustain long-term reductions in pneumococcal colonization.
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