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Attitudes of pregnant women in the Dominican Republic towards a future maternal Group B Streptococcus vaccine
Job, Megan J; Kim, Diane; Acosta, Francia; Valera, Sandra; Fernandez, Anabel; Laycock, Katherine M; Ratner, Adam J; Steenhoff, Andrew P; Feemster, Kristen; Geoghegan, Sarah
INTRODUCTION/BACKGROUND:Current protocols aim to prevent some infant GBS infection through screening and peripartum antibiotics, however such strategies cannot be widely implemented in resource-limited settings. On the other hand, maternal vaccines in development against Group B Streptococcus (GBS) can provide a feasible universal approach. The success of any vaccine will depend on uptake in the population. Rates of maternal GBS colonization in the Dominican Republic (DR) and Caribbean region are among the highest in the world, but little is known about attitudes towards maternal vaccines in this region. METHODS:A cross-sectional, multicenter, mixed-methodology survey evaluated facilitators and barriers to maternal immunization and acceptability of a hypothetical Group B Streptococcus vaccine among pregnant women in three hospitals in the DR. RESULTS:Six-hundred and fifty women completed the survey of whom 85 % had never heard of GBS. Following receipt of information about GBS and a vaccine, 94 % of women stated that they would be likely or very likely to receive a vaccine. Being 18 years or younger was associated with a lower likelihood of GBS vaccine receipt (AOR 0.32, 95 % CI 0.14-0.69). Being born in the DR was associated with a higher likelihood of GBS vaccine receipt (AOR 2.73, 95 % CI 1.25-5.97). Among women who were unlikely to receive the vaccine, uncertainty about potential harm from a novel vaccine was the prominent theme elicited from free text responses. CONCLUSION/CONCLUSIONS:There was a high level of acceptance of a future GBS vaccine among this sample of pregnant women in the DR. However, knowledge of vaccines and vaccine-preventable diseases was low, and most women had concerns about the safety of new vaccines. Interventions that strengthen existing maternal immunisation infrastructures, including increasing education of pregnant women about vaccines, will aid the successful implementation of a future GBS vaccine.
PMID: 39126829
ISSN: 1873-2518
CID: 5687402
Cefiderocol Red Wine Urine Syndrome in Pediatric Patients: A Multicenter Case Series
Shapiro, Kate; Ungar, Stephanie P; Krugman, Jessica; McGarrity, Orlagh; Cross, Shane J; Indrakumar, Bairavi; Hatcher, James; Ratner, Adam J; Wolf, Joshua
Cefiderocol is a novel cephalosporin antibiotic with activity against multidrug-resistant gram-negative bacteria and limited pediatric experience. This case series describes 3 immunocompromised children receiving blood transfusion who developed benign red or purple urine with administration of cefiderocol. Interaction with iron from blood products is a possible mechanism. It is important to recognize this phenomenon and distinguish it from hematuria to avoid unnecessary diagnostic testing.
PMID: 37922468
ISSN: 1532-0987
CID: 5607072
Group B Streptococcal Infections
Chapter by: Ratner, Adam J.; Nizet, Victor; Puopolo, Karen Marie
in: Remington and Klein's Infectious Diseases of the Fetus and Newborn Infant, Ninth Edition by
[S.l.] : Elsevier, 2024
pp. 348-378.e11
ISBN: 9780323795272
CID: 5715692
A group B Streptococcus indexed transposon mutant library to accelerate genetic research on an important perinatal pathogen
Bhavana, Venkata H; Hillebrand, Gideon H; Gopalakrishna, Kathyayini P; Rapp, Rebekah A; Ratner, Adam J; Tettelin, Hervé; Hooven, Thomas A
Group B Streptococcus (GBS) is a significant global cause of serious infections, most of which affect pregnant women, newborns, and infants. Studying GBS genetic mutant strains is a valuable approach for learning more about how these infections are caused and is a key step toward developing more effective preventative and treatment strategies. In this resource report, we describe a newly created library of defined GBS genetic mutants, containing over 1,900 genetic variants, each with a unique disruption to its chromosome. An indexed library of this scale is unprecedented in the GBS field; it includes strains with mutations in hundreds of genes whose potential functions in human disease remain unknown. We have made this resource freely available to the broader research community through deposition in a publicly funded bacterial maintenance and distribution repository.
PMCID:10714824
PMID: 37933989
ISSN: 2165-0497
CID: 5620302
Genomic Analysis of Group B Streptococcus Carriage Isolates From Botswana Reveals Distinct Local Epidemiology and Identifies Novel Strains
Hanze Villavicencio, Karen L; Job, Megan J; Burghard, Anne Claire; Taffet, Allison; Banda, Francis M; Vurayai, Moses; Mokomane, Margaret; Arscott-Mills, Tonya; Mazhani, Tiny; Nchingane, Seeletso; Thomas, Brady; Steenhoff, Andrew P; Ratner, Adam J
In pregnant people colonized with group B Streptococcus (GBS) in Botswana, we report the presence/expansion of sequence types 223 and 109, a low rate of erythromycin resistance, and 3 novel sequence types. These data highlight the importance of local epidemiologic studies of GBS, a significant source of neonatal disease.
PMCID:10588617
PMID: 37869411
ISSN: 2328-8957
CID: 5736222
Capsule production promotes Group B Streptococcus intestinal colonization
Vaz, Michelle J; Dongas, Sophia; Ratner, Adam J
Late-onset disease is the most common clinical presentation of Group B Streptococcus (GBS) infection during infancy, and gastrointestinal (GI) colonization is an important precursor. Previously, we described a murine model of postnatal GBS GI colonization that resulted in sustained colonization and progression to invasive disease. Capsular polysaccharide is an important GBS virulence factor. Vaccines based on a subset of capsular serotypes are in clinical trials. However, little is known regarding the role of specific GBS capsular serotypes in GI colonization. We examined the role of GBS capsule in GI colonization using capsule-producing and acapsular strains derived from GBS strain A909 (serotype Ia) in a murine model. Using isogenic GBS strains differing only in capsular serotypes, we explored the role of specific serotypes in GI colonization by determining competitive indices during cocolonization. We found that GBS A909 colonizes the murine GI tract without causing invasive disease. In monocolonization experiments, there was colonization persistence with the capsule-producing strain (100%) compared to the acapsular mutant strain (13%). In cocolonization experiments, the capsule-producing strain outcompeted its isogenic acapsular mutant, with a geometric mean competitive index of 8, 95% confidence interval (CI) [1.7, 38.9] in the colon at 7 days post-colonization. A909 expressing its native serotype Ia capsule outcompeted an isogenic mutant that expresses serotype III capsule, with a geometric mean competitive index of 2.5, 95% CI [1.2, 5.1] in the colon at 7 days post-colonization. Thus, polysaccharide capsule production enhances GBS GI colonization in vivo. In an A909 genetic background, the production of a serotype Ia capsule provides a competitive advantage over an isogenic strain producing type III capsule. The murine model is a valuable tool to understand the role of GBS capsule types in GI colonization. IMPORTANCE The establishment of GBS intestinal colonization is believed to be a critical precursor to late-onset disease in neonates, which has a significant impact on neurodevelopment outcomes in this population. Our prior work described a murine model of postnatal Group B Streptococcus (GBS) acquisition and invasive disease. Using this model, we explored the importance of GBS polysaccharide capsule production on gastrointestinal colonization. We found that the expression of capsule (compared to isogenic acapsular strains) provides an advantage in intestinal colonization and, importantly, that capsule type Ia has an advantage over capsule type III in a GBS A909 strain background. We speculate that specific serotypes may differ in colonization fitness, which may play a role in serotype distribution in neonatal disease.
PMCID:10655599
PMID: 37732775
ISSN: 2165-0497
CID: 5614072
Characterization of tigurilysin, a novel human CD59-specific cholesterol-dependent cytolysin, reveals a role for host specificity in augmenting toxin activity
Shahi, Ifrah; Dongas, Sophia A; Ilmain, Juliana K; Torres, Victor J; Ratner, Adam J
Cholesterol-dependent cytolysins (CDCs) are a large family of pore-forming toxins, produced by numerous Gram-positive pathogens. CDCs depend on host membrane cholesterol for pore formation; some CDCs also require surface-associated human CD59 (hCD59) for binding, conferring specificity for human cells. We purified a recombinant version of a putative CDC encoded in the genome of Streptococcus oralis subsp. tigurinus, tigurilysin (TGY), and used CRISPR/Cas9 to construct hCD59 knockout (KO) HeLa and JEG-3 cell lines. Cell viability assays with TGY on wild-type and hCD59 KO cells showed that TGY is a hCD59-dependent CDC. Two variants of TGY exist among S. oralis subsp. tigurinus genomes, only one of which is functional. We discovered that a single amino acid change between these two TGY variants determines its activity. Flow cytometry and oligomerization Western blots revealed that the single amino acid difference between the two TGY isoforms disrupts host cell binding and oligomerization. Furthermore, experiments with hCD59 KO cells and cholesterol-depleted cells demonstrated that TGY is fully dependent on both hCD59 and cholesterol for activity, unlike other known hCD59-dependent CDCs. Using full-length CDCs and toxin constructs differing only in the binding domain, we determined that having hCD59 dependence leads to increased lysis efficiency, conferring a potential advantage to organisms producing hCD59-dependent CDCs.
PMID: 37702594
ISSN: 1465-2080
CID: 5593542
Vaginal carriage of Haemophilus influenzae in a non-pregnant reproductive-age population
Limaye, Meghana A; Brubaker, Sara; Randis, Tara M; Ratner, Adam J
BACKGROUND:Haemophilus influenzae (Hi) is an emerging cause of early onset neonatal sepsis, but mechanisms of transmission are not well understood. We aimed to determine the prevalence of vaginal carriage of Hi in reproductive age women and to examine behavioral and demographic characteristics associated with its carriage. METHODS:) value < 35 were defined as positive. Sanger sequencing confirmed the presence of hpd. Behavioral and demographic characteristics associated with vaginal carriage of Hi were examined. RESULTS:415 samples were available. 315 (75.9%) had sufficient bacterial DNA and were included. 14 (4.4%) were positive for hpd. There were no demographic or behavioral differences between the women with Hi vaginal carriage and those without. There was no difference in history of bacterial vaginosis, vaginal microbiome community state type, or presence of Group B Streptococcus in women with and without vaginal carriage of Hi. CONCLUSION:Hi was present in vaginal lavage specimens of 4.4% of this cohort. Hi presence was unrelated to clinical or demographic characteristics, though the relatively small number of positive samples may have limited power to detect such differences.
PMCID:10197216
PMID: 37208594
ISSN: 1471-2180
CID: 5503682
Maternity care provider acceptance of a future Group B Streptococcus vaccine - A qualitative study in three countries
Geoghegan, Sarah; Acosta, Francia; Stephens, Laura C; Gillan, Hanah; Valera, Sandra; Drew, Richard J; Eogan, Maeve; Ratner, Adam J; Steenhoff, Andrew P; Butler, Karina M; Feemster, Kristen A
INTRODUCTION/BACKGROUND:There are vaccines in clinical trials that target the bacterium Group B Streptococcus (GBS). When approved, GBS vaccines will be intended for administration to pregnant women to prevent infection in their infants. The success of any vaccine will depend on its' uptake in the population. Experience with prior maternal vaccines, e.g. influenza, Tdap and COVID-19 vaccines, teaches us that acceptance of vaccines, especially if novel, is challenging for pregnant women, and that provider recommendation is a key driver of vaccine uptake. METHODS:This study investigated attitudes of maternity care providers towards the introduction of a GBS vaccine in three countries (the United States (US), Ireland, and the Dominican Republic (DR)) with different GBS prevalence and prevention practices. Semi-structured interviews with maternity care providers were transcribed and coded for themes. The constant comparative method, and inductive theory building were used to develop conclusions. RESULTS:Thirty-eight obstetricians, 18 general practitioners and 14 midwives participated. There was variability in provider attitudes towards a hypothetical GBS vaccine. Responses ranged from enthusiasm to doubts over the need for a vaccine. Attitudes were influenced by perceived additional benefits of a vaccine over current strategy and confidence in the safety of vaccines during pregnancy. Knowledge, experience and approaches to GBS prevention differed geographically and according to provider type, and influenced how participants assessed the risks and benefits of a GBS vaccine. CONCLUSION/CONCLUSIONS:Maternity care providers are engaged in the topic of GBS management and there is opportunity to leverage attitudes and beliefs that will support a strong recommendation for a GBS vaccine. However, knowledge of GBS, and of the limitations of current prevention strategies vary among providers in different regions, and between different provider types. Targeted educational efforts with antenatal providers should focus on highlighting safety data the potential benefits of vaccination over current strategies.
PMID: 36803900
ISSN: 1873-2518
CID: 5448102
Host inflammatory dynamics reveal placental immune modulation by Group B Streptococcus during pregnancy
Kuperwaser, Felicia; Avital, Gal; Vaz, Michelle J; Noble, Kristen N; Dammann, Allison N; Randis, Tara M; Aronoff, David M; Ratner, Adam J; Yanai, Itai
Group B Streptococcus (GBS) is a pathobiont that can ascend to the placenta and cause adverse pregnancy outcomes, in part through production of the toxin β-hemolysin/cytolysin (β-h/c). Innate immune cells have been implicated in the response to GBS infection, but the impact of β-h/c on their response is poorly defined. We show that GBS modulates innate immune cell states by subversion of host inflammation through β-h/c, allowing worse outcomes. We used an ascending mouse model of GBS infection to measure placental cell state changes over time following infection with a β-h/c-deficient and isogenic wild type GBS strain. Transcriptomic analysis suggests that β-h/c-producing GBS elicit a worse phenotype through suppression of host inflammatory signaling in placental macrophages and neutrophils, and comparison of human placental macrophages infected with the same strains recapitulates these results. Our findings have implications for identification of new targets in GBS disease to support host defense against pathogenic challenge.
PMCID:9996236
PMID: 36744393
ISSN: 1744-4292
CID: 5429472