Immunogenicity at delivery after Tdap vaccination in successive pregnancies.

Background: Tetanus, diphtheria, acellular pertussis (Tdap) vaccination is recommended to be administered in every pregnancy. Although the safety of this strategy has been confirmed, the immunogenicity of Tdap vaccination in two successive pregnancies has not yet been described. This study investigated Tdap-specific immunity levels and transplacental transfer in two successive pregnancies after repeated Tdap-vaccination. Methods: Women enrolled in prior studies on Tdap vaccination during pregnancy were invited to participate in a follow-up study if they became pregnant again. Women who received a Tdap vaccine in both pregnancies were considered for this analysis. Tdap-specific total IgG and IgG subclasses were measured with a multiplex immunoassay. Results: In total, 27 participants with a mean interval between deliveries of 2.4 years were included in the analysis. In maternal serum, Tdap-specific total IgG levels were comparable at both deliveries whereas in cord serum, all Tdap-specific total IgG antibody levels were reduced at the second compared to the first delivery. This was largely reflected in the IgG1 levels in maternal and cord serum. Transplacental transfer ratios of total IgG and IgG1 were also mostly reduced in the second compared to the first pregnancy. Conclusion: This study reports for the first time Tdap-specific total IgG and IgG subclass levels and transfer ratios after repeated Tdap vaccination in successive pregnancies. We found reduced transfer of most Tdap-specific IgG and IgG1 antibodies in the successive pregnancy. As pertussis-specific antibodies wane quickly, Tdap vaccination in each pregnancy remains beneficial. However, more research is needed to understand the impact of closely spaced booster doses during pregnancy on early infant protection against pertussis.

Rifampicin resistance conferring mutations among Mycobacterium tuberculosis strains in Rwanda.

Background: The World Health Organization-endorsed phenotypic and genotypic drug-susceptibility testing (gDST/pDST) assays for the detection of rifampicin-resistant (RR) tuberculosis (TB), may miss some clinically relevant rpoB mutants, including borderline mutations and mutations outside the gDST-targeted hotspot region. Sequencing of the full rpoB gene is considered the reference standard for rifampicin DST but is rarely available in RR-TB endemic settings and when done indirectly on cultured isolates may not represent the full spectrum of mutations. Hence, in most such settings, the diversity and trends of rpoB mutations remain largely unknown. Methods: This retrospective study included rpoB sequence data from a longitudinal collection of RR-TB isolates in Rwanda across 30 years (1991-2021). Results: Of 540 successfully sequenced isolates initially reported as RR-TB, 419 (77.6%) had a confirmed RR conferring mutation. The Ser450 Leu mutation was predominant throughout the study period. The Val170Phe mutation, not covered by rapid gDST assays, was observed in only four patients, three of whom were diagnosed by pDST. Along with the transition from pDST to rapid gDST, borderline RR-associated mutations, particularly Asp435Tyr, were detected more frequently. Borderline mutants were not associated with HIV status but presented lower odds of having rpoA-C compensatory mutations than other resistance-conferring mutations. Conclusion: Our analysis showed changes in the diversity of RR-TB conferring mutations throughout the study period that coincided with the switch of diagnostic tools to rapid gDST. The study highlights the importance of rapid molecular diagnostics reducing phenotypic bias in the detection of borderline rpoB mutations while vigilance for non-rifampicin resistance determinant region mutations is justified in any setting.

The Effects of COVID-19 Vaccination on Lactating Women: A Systematic Review of the Literature.

Objectives: The availability of new vaccines against COVID-19 urges for guidance about vaccination during lactation. We aimed to review the literature to get an insight into the effects of COVID-19 vaccination on lactating women. Design: Systematic review. Data Sources: We searched Ovid Embase Classic+Embase, PubMed and BioMed Central for articles published between December 1st 2020 and December 31st 2021. Review Methods: The search strategy contained terms and combinations related to COVID-19 vaccination during lactation, including the MeSH terms "COVID-19", "COVID-19 Vaccines", "SARS-CoV-2", "Lactation", "Breast Feeding", "Pregnancy" and "Postpartum period". The database search was completed with a manual search of the reference lists of included articles. Data concerning country, study period, number of participants, type of applied vaccine, time points of sampling and outcome measures were collected from the selected manuscripts. The data are summarized and synthesized in a descriptive way. Results: 30 manuscripts were included in this review. Data on safety of COVID-19 vaccination during lactation indicate no severe vaccine-related local and systemic reactions, both after first and second dose, neither in the mother nor the nursing child. No significant amount of vaccine components seems to appear in breast milk. Milk supply data after vaccination are inconclusive as there are no quantitative data available. Some women however observe a temporary increase or reduction in milk supply, without long-term effects. All prospective cohort studies demonstrated the presence of SARS-CoV-2-specific antibodies in breast milk of nursing mothers vaccinated against SARS-CoV-2. Nearly all studies were conducted with mRNA vaccines. Conclusion: There is evidence that the administration of a COVID-19 vaccine is safe and poses no additional risk to the breastfeeding woman or the breastfed baby. After vaccination of the mother during the lactation period, antibodies appear in the milk, which could protect the infant against COVID-19. Professional associations and government health authorities should therefore recommend offering COVID-19 vaccines to breastfeeding women, as the potential benefits of maternal vaccination while breastfeeding outweigh the risks.