ABSTRACT
BACKGROUND: We studied humoral responses after coronavirus disease 2019 (COVID-19) vaccination across varying causes of immunodeficiency. METHODS: Prospective study of fully vaccinated immunocompromised adults (solid organ transplant [SOT], hematologic malignancy, solid cancers, autoimmune conditions, human immunodeficiency virus [HIV]) versus nonimmunocompromised healthcare workers (HCWs). The primary outcome was the proportion with a reactive test (seropositive) for immunoglobulin G to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain. Secondary outcomes were comparisons of antibody levels and their correlation with pseudovirus neutralization titers. Stepwise logistic regression was used to identify factors associated with seropositivity. RESULTS: A total of 1271 participants enrolled: 1099 immunocompromised and 172 HCW. Compared with HCW (92.4% seropositive), seropositivity was lower among participants with SOT (30.7%), hematological malignancies (50.0%), autoimmune conditions (79.1%), solid tumors (78.7%), and HIV (79.8%) (P < .01). Factors associated with poor seropositivity included age, greater immunosuppression, time since vaccination, anti-CD20 monoclonal antibodies, and vaccination with BNT162b2 (Pfizer) or adenovirus vector vaccines versus messenger RNA (mRNA)-1273 (Moderna). mRNA-1273 was associated with higher antibody levels than BNT162b2 or adenovirus vector vaccines after adjusting for time since vaccination, age, and underlying condition. Antibody levels were strongly correlated with pseudovirus neutralization titers (Spearman râ =â 0.89, Pâ <â .0001), but in seropositive participants with intermediate antibody levels, neutralization titers were significantly lower in immunocompromised individuals versus HCW. CONCLUSIONS: Antibody responses to COVID-19 vaccines were lowest among SOT and anti-CD20 monoclonal recipients, and recipients of vaccines other than mRNA-1273. Among those with intermediate antibody levels, pseudovirus neutralization titers were lower in immunocompromised patients than HCWs. Additional SARS-CoV-2 preventive approaches are needed for immunocompromised persons, which may need to be tailored to the cause of immunodeficiency.
Subject(s)
COVID-19 , HIV Infections , Adult , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , HIV Infections/complications , Humans , Immunocompromised Host , Prospective Studies , SARS-CoV-2 , VaccinationABSTRACT
BACKGROUND: Pregnant women were excluded from investigational trials of COVID-19 vaccines. Limited data are available to inform pregnant and postpartum women on their decisions to receive a COVID-19 vaccine. METHODS: The goal of this observational, prospective cohort study is to evaluate the immunogenicity and safety of various Emergency Use Authorization (EUA) or licensed COVID-19 vaccines administered to pregnant or lactating women and describe the transplacental antibody transfer and kinetics of antibodies in mothers and infants. The study is adaptive, allowing additional groups to be added as new vaccines or vaccine regimens are authorized. Up to 20 clinical research institutions in the United States (U.S.) will be included. Approximately 200 pregnant women and 65 postpartum women will be enrolled per EUA or licensed COVID-19 vaccine formulation in the U.S. This study will include pregnant and postpartum women of all ages with and without chronic medical conditions. Their infants will be enrolled and followed beginning at birth in the pregnant cohort and beginning at the earliest possible time point in the postpartum cohort. Blood samples will be collected for immunogenicity outcomes and pregnancy and birth outcomes assessed among women and infants. Primary analyses will be descriptive and done by vaccine type and/or platform. DISCUSSION: Given the long-standing and legitimate challenges of enrolling pregnant individuals into clinical trials early in the vaccine development pipeline, this study protocol describes our current study and provides a template to inform the collection of data for pregnant individuals receiving COVID-19 or other vaccines. TRIAL REGISTRATION: NCT05031468 .
Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Female , Humans , Infant , Infant, Newborn , Lactation , Multicenter Studies as Topic , Observational Studies as Topic , Pregnancy , Prospective StudiesABSTRACT
OBJECTIVE: To ascertain the prevalence of Trichomonas vaginalis and investigate associations between trichomoniasis, endometritis and sequelae among women with pelvic inflammatory disease (PID). METHODS: We assessed the prevalence of trichomoniasis identified via wet mount and its association with histologically confirmed endometritis, infertility and recurrent PID among 647 women in the PID Evaluation and Clinical Health (PEACH) study. Participants were treated for clinically suspected PID and followed for a mean of 84 months for incident sequelae. Analyses were adjusted for age, race, Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and bacterial vaginosis. Additional adjustments were incorporated for history of infertility (models of pregnancy and infertility), history of PID (recurrent PID), and self-reported partner treatment and intercourse between baseline and 30-day follow-up (persistent endometritis). RESULTS: T. vaginalis was present in the vagina of 12.8% of women. The odds of having endometritis at baseline were twice as high among women with trichomoniasis as compared with those without (adjusted OR (AOR): 1.9, 95% CI 1.0 to 3.3). Persistent endometritis was highly prevalent at 30 days (52.1%) and more common among women with baseline trichomoniasis (AOR: 2.6, 95% CI 0.7 to 10.1), although non-significantly. Infertility and recurrent PID were more common among women with trichomoniasis, while rates of pregnancy and live birth were lower. CONCLUSIONS: T. vaginalis was frequently isolated from the vagina of women with PID in the PEACH cohort. Wet mount microscopy for the identification of motile trichomonads was standard practice at the time of the PEACH study, but likely resulted in an underestimation of true T. vaginalis prevalence. Our findings of modest, although non-significant, prospective associations between trichomoniasis and sequelae are novel and underscore the need for additional investigation into whether T. vaginalis may play an aetiological role in adverse reproductive and gynaecological outcomes.
Subject(s)
Endometritis/epidemiology , Infertility, Female/epidemiology , Pelvic Inflammatory Disease/epidemiology , Pregnancy Rate , Trichomonas Vaginitis/epidemiology , Adult , Chlamydia Infections/epidemiology , Chlamydia trachomatis , Female , Gonorrhea/epidemiology , Humans , Live Birth/epidemiology , Mycoplasma Infections/epidemiology , Mycoplasma genitalium , Pelvic Inflammatory Disease/drug therapy , Pregnancy , Recurrence , Risk Factors , Trichomonas vaginalis , United States/epidemiology , Vaginosis, Bacterial/epidemiologyABSTRACT
Breastfeeding (BF) women are an important population for biomedical HIV prevention strategies, but they are rarely included in trials. The 25-mg dapivirine vaginal ring (VR) reduced women's risk of sexually transmitted HIV infection in two phase 3 trials conducted in Africa. We conducted a phase 1, open-label study (MTN-029/IPM 039) of dapivirine VR use among lactating women in Pittsburgh, PA, and Birmingham, AL, USA. MTN-029/IPM 039 enrolled 16 healthy adult women who had already weaned their infants but were still able to express breast milk. Women were instructed to use the VR continuously for 14 days and provided milk, plasma, and cervicovaginal fluid (CVF) samples for pharmacological analysis. No infants were exposed to the drug, but infant dosage was estimated according to FDA guidance. Adverse events (AEs) were collected at all contacts. The study was completed with 100% participant retention. Median dapivirine concentrations were 676 pg/ml in breast milk, 327 pg/ml in plasma (milk/plasma ratio â¼2.0), and 36.25 ng/mg in CVF. Six participants experienced 10 total AEs, none of which required VR discontinuation. The estimated mean daily infant dosage was 74.3 ng/kg/day. In this first study of dapivirine exposure during lactation, dapivirine VR use was associated with lower concentrations of detectable dapivirine in milk and plasma than in CVF samples and a favorable safety profile. Estimated daily levels of infant dapivirine exposure were also low. Additional studies are needed to evaluate longer periods of dapivirine VR use among BF mother-infant pairs living in regions with higher incidence of sexually transmitted HIV infection. (This study has been registered at ClinicalTrials.gov under registration no. NCT02808949.).
Subject(s)
Anti-HIV Agents/pharmacokinetics , HIV Infections/prevention & control , Milk, Human/chemistry , Pyrimidines/pharmacokinetics , Administration, Intravaginal , Adult , Anti-HIV Agents/blood , Female , Humans , Lactation/metabolism , Pyrimidines/blood , Young AdultABSTRACT
BACKGROUND: Empiric therapy for urinary tract infection is difficult in postmenopausal women because of the higher rates of confounding lower urinary tract symptoms and differential resistance profiles of uropathogens in this population. OBJECTIVE: The objective of the study was to determine the least costly strategy for treatment of postmenopausal women with the primary complaint of dysuria. STUDY DESIGN: We performed a cost minimization analysis modeling the following clinical options: (1) empiric antibiotic therapy followed by urine culture, (2) urinalysis with empiric antibiotic therapy only if positive nitrites and leukocyte esterase, or (3) waiting for culture prior to initiating antibiotics. For all strategies we included nitrofurantoin, trimethoprim/sulfamethoxazole, fosfomycin, ciprofloxacin, or cephalexin. Pathogens included Escherichia coli, Enterococcus faecalis, Klebsiella pneumonaie, or Proteus mirabalis. Pathogens, resistance, treatment success, and medication side effects were specific to postmenopausal women. RESULTS: Cost minimization modeling with TreeAge Pro assumed 73.4% of urinary tract infections were caused by Escherichia coli with 24.4% resistance to nitrofurantoin, trimethoprim/sulfamethoxazole. With our assumptions, empiric antibiotics with nitrofurantoin, trimethoprim/sulfamethoxazole was the least costly approach ($89.64/patient), followed by waiting for urine culture ($97.04/patient). Except for empiric antibiotics with fosfomcyin, empiric antibiotics was always less costly than using urinalysis to discriminate antibiotic use. This is due to the cost of urinalysis ($38.23), high rate of both urinary tract infection (91%), and positive urinalysis (69.3%) with dysuria in postmenopausal women and resultant high rate of antibiotic use with or without urinalysis. Options with fosfomycin were the most expensive because of the highest drug costs ($98/dose), and tornado analyses showed fosfomycin cost was the most impactful variable for model outcomes. Sensitivity analyses showed empiric fosfomycin became the least costly option if drug costs were $25.80, a price still more costly than almost all modeled baseline drug costs. This outcome was largely predicated on low resistance to fosfomycin. Conversely, ciprofloxacin was never the least costly option because of higher resistance and side effect cost, even if the drug cost was $0. We modeled 91% positive urine culture rate in postmenopausal women with dysuria; waiting for the urine culture prior to treatment would be the least costly strategy in a population with a predicted positive culture rate of <65%. CONCLUSION: The least costly strategy was empiric antibiotics with nitrofurantoin and trimethoprim/sulfamethoxazole, followed by waiting on culture results. Local resistance patterns will have an impact on cost minimization strategies. Empiric fosfomycin would be least costly with reduced drug costs, even at a level at which drug costs were higher than almost all other antibiotics. In a population with high posttest probability of positive urine culture, urinalysis adds unnecessary cost. Antibiotic stewardship programs should continue efforts to decrease fluoroquinolone use because of high resistance, side effects, and increased cost.
Subject(s)
Anti-Bacterial Agents/economics , Anti-Bacterial Agents/therapeutic use , Dysuria/economics , Postmenopause , Urinalysis/economics , Urinary Tract Infections/diagnosis , Costs and Cost Analysis , Decision Trees , Drug Combinations , Female , Fosfomycin/economics , Fosfomycin/therapeutic use , Humans , Nitrofurantoin/economics , Nitrofurantoin/therapeutic use , Sulfamethizole/economics , Sulfamethizole/therapeutic use , Trimethoprim/economics , Trimethoprim/therapeutic use , Urinary Tract Infections/drug therapy , Urinary Tract Infections/microbiologyABSTRACT
The mechanism by which the Zika virus can cause fetal microcephaly is not known. Reports indicate that Zika is able to evade the normal immunoprotective responses of the placenta. Microcephaly has genetic causes, some associated with maternal exposures including radiation, tobacco smoke, alcohol, and viruses. Two hypotheses regarding the role of the placenta are possible: one is that the placenta directly conveys the Zika virus to the early embryo or fetus. Alternatively, the placenta itself might be mounting a response to the exposure; this response might be contributing to or causing the brain defect. This distinction is crucial to the diagnosis of fetuses at risk and the design of therapeutic strategies to prevent Zika-induced teratogenesis.
Subject(s)
Fetus/virology , Microcephaly/virology , Placenta , Teratogens , Zika Virus/pathogenicity , Female , Humans , Microcephaly/prevention & control , Placenta/immunology , Placenta/virology , PregnancyABSTRACT
Lactation studies are necessary evaluations of medications for reproductive-age women. We evaluated pharmacokinetics (PK), pharmacodynamics, safety, and adherence profiles associated with 7 days of 1% tenofovir (TFV) vaginal gel use during lactation. Tenofovir levels (maternal/infant serum, milk) and anti-HIV activity (milk), adverse events (AEs), and adherence were measured for 17 HIV-1-seronegative breast-feeding mother-infant pairs. Tenofovir use was well-tolerated and detected at low levels in maternal serum, milk, and infant serum but demonstrated no anti-HIV activity in milk.
Subject(s)
Anti-HIV Agents/blood , Milk, Human/metabolism , Tenofovir/blood , Tenofovir/pharmacokinetics , Adult , Breast Feeding , Female , HIV Infections/blood , HIV Infections/drug therapy , HIV Infections/metabolism , HIV-1/drug effects , Humans , Infant , Lactation/metabolism , Mothers , Tenofovir/therapeutic use , Vaginal Creams, Foams, and Jellies/pharmacokinetics , Vaginal Creams, Foams, and Jellies/therapeutic use , Young AdultABSTRACT
This report outlines recommendations for the clinical use of the three smallpox vaccines stored in the U.S. Strategic National Stockpile for persons who are exposed to smallpox virus or at high risk for smallpox infection during a postevent vaccination program following an intentional or accidental release of the virus. No absolute contraindications exist for smallpox vaccination in a postevent setting. However, several relative contraindications exist among persons with certain medical conditions. CDC recommendations for smallpox vaccine use were developed in consideration of the risk for smallpox infection, risk for an adverse event following vaccination, and benefit from vaccination. Smallpox vaccines are made from live vaccinia viruses that protect against smallpox disease. They do not contain variola virus, the causative agent of smallpox. The three smallpox vaccines stockpiled are ACAM2000, Aventis Pasteur Smallpox Vaccine (APSV), and Imvamune. Surveillance and containment activities including vaccination with replication-competent smallpox vaccine (i.e., vaccine viruses capable of replicating in mammalian cells such as ACAM2000 and APSV) will be the primary response strategy for achieving epidemic control. Persons exposed to smallpox virus are at high risk for developing and transmitting smallpox and should be vaccinated with a replication-competent smallpox vaccine unless severely immunodeficient. Because of a high likelihood of a poor immune response and an increased risk for adverse events, smallpox vaccination should be avoided in persons with severe immunodeficiency who are not expected to benefit from vaccine, including bone marrow transplant recipients within 4 months of transplantation, persons infected with HIV with CD4 cell counts <50 cells/mm3, and persons with severe combined immunodeficiency, complete DiGeorge syndrome, and other severely immunocompromised states requiring isolation. If antivirals are not immediately available, it is reasonable to consider the use of Imvamune in the setting of a smallpox virus exposure in persons with severe immunodeficiency. Persons without a known smallpox virus exposure might still be at high risk for developing smallpox infection depending on the magnitude of the outbreak and the effectiveness of the public health response. Such persons will be defined by public health authorities and should be screened for relative contraindications to smallpox vaccination. Relative contraindications include atopic dermatitis (eczema), HIV infection (CD4 cell counts of 50-199 cells/mm3), other immunocompromised states, and vaccine or vaccine-component allergies. Persons with relative contraindications should be vaccinated with Imvamune when available and authorized for use by the Food and Drug Administration. These recommendations will be updated as new data on smallpox vaccines become available and further clinical guidance for other medical countermeasures including antivirals is developed.
Subject(s)
Immunization Programs/standards , Practice Guidelines as Topic , Smallpox Vaccine/administration & dosage , Smallpox/prevention & control , Biohazard Release , Bioterrorism , Disaster Planning , Humans , United StatesABSTRACT
OBJECTIVE: This study aims to identify risk factors for cesarean delivery (CD) surgical site infection (SSI). study design: Retrospective analysis of 2,739 CDs performed at the University of Pittsburgh in 2011. CD SSIs were defined using National Healthcare Safety Network (NHSN) criteria. Chi-square test and t-test were used for bivariate analyses and multivariate logistic regression was used to identify SSI risk factors. RESULTS: Of 2,739 CDs, 178 (6.5%) were complicated by SSI. Patients with a SSI were more likely to have Medicaid, have resident physicians perform the CD, an American Society of Anesthesiologists (ASA) class of ≥ 3, chorioamnionitis, tobacco use, and labor before CD. In multivariable analysis, labor (odds ratio [OR], 2.35; 95% confidence interval [95% CI], 1.65-3.38), chorioamnionitis (OR, 2.24; 95% CI, 1.25-3.83), resident teaching service (OR, 2.15; 95% CI, 1.54-3.00), tobacco use (OR, 1.70; 95% CI, 1.04-2.70), ASA class ≥ 3 (OR, 1.61; 95% CI, 1.06-2.39), and CDs performed for nonreassuring fetal status (OR, 0.43; 95% CI, 0.26-0.67) were significantly associated with CD SSI. CONCLUSION: Multiple patient, provider, and procedure-specific risk factors contribute to CD SSI risk which may be targeted in infection-control efforts.
Subject(s)
Cesarean Section , Chorioamnionitis/epidemiology , Fetal Distress/epidemiology , Labor, Obstetric , Medicaid/statistics & numerical data , Surgical Wound Infection/epidemiology , Tobacco Use/epidemiology , Adult , Blood Loss, Surgical/statistics & numerical data , Female , Humans , Insurance, Health/statistics & numerical data , Internship and Residency/statistics & numerical data , Logistic Models , Multivariate Analysis , Obstetrics/education , Odds Ratio , Pregnancy , Private Practice/statistics & numerical data , Retrospective Studies , Risk Factors , United States/epidemiology , Uterine Hemorrhage/epidemiology , Young AdultABSTRACT
AIMS: Physiological changes in pregnancy are expected to alter the pharmacokinetics of various drugs. The objective of this study was to evaluate systematically the pharmacokinetics of oseltamivir (OS), a drug used in the treatment of influenza during pregnancy. METHODS: A multicentre steady-state pharmacokinetic study of OS was performed in 35 non-pregnant and 29 pregnant women. Plasma concentration-time profiles were analyzed using both non-compartmental and population pharmacokinetic modelling (pop PK) and simulation approaches. A one compartment population pharmacokinetic model with first order absorption and elimination adequately described the pharmacokinetics of OS. RESULTS: The systemic exposure of oseltamivir carboxylate (OC, active metabolite of OS) was reduced approximately 30 (19-36)% (P < 0.001) in pregnant women. Pregnancy significantly (P < 0.001) influenced the clearance (CL/F) and volume of distribution (V/F) of OC. Both non-compartmental and population pharmacokinetic approaches documented approximately 45 (23-62)% increase in clearance (CL/F) of OC during pregnancy. CONCLUSION: Based on the decrease in exposure of the active metabolite, the currently recommended doses of OS may need to be increased modestly in pregnant women in order to achieve comparable exposure with that of non-pregnant women.
Subject(s)
Antiviral Agents/pharmacokinetics , Oseltamivir/analogs & derivatives , Oseltamivir/pharmacokinetics , Adolescent , Adult , Antiviral Agents/blood , Computer Simulation , Female , Humans , Middle Aged , Models, Biological , Oseltamivir/blood , Pregnancy , Young AdultABSTRACT
OBJECTIVE: To delineate the effects of text messages sent to pregnant women to promote preventive health beliefs and behaviors. STUDY DESIGN: A prospective cohort analysis was performed among women who participated in a randomized, controlled trial aimed at improving preventive health. Participants (158 pregnant women enrolled from 2010-2012) received 12 weekly text messages encouraging preventive health behaviors (tobacco cessation, condom use for disease prevention, nutrition optimization, seat belt use, breastfeeding). Pre- and postintervention surveys assessed preventive health beliefs and practices. RESULTS: At follow-up, participants agreed that receiving text messages changed their beliefs about targeted preventive health behaviors: smoking (50%), sexually transmitted disease prevention (72%), prenatal vitamins (83%), seat belt use (68%), nutritious foods (84%), and breastfeeding (68%). Many participants reported more frequent engagement in target behaviors at follow-up than at baseline: decreased tobacco use (among 41% of smokers), more consistent condom use (among 7% of sexually active participants), more prenatal vitamin intake (32%), more frequent seatbelt use (32%), more frequent healthy food intake (41%), and intention to breastfeed longer (21%). CONCLUSION: Pregnant women receiving text messages promoting preventive health reported improvements in targeted beliefs and behaviors, suggesting that text messaging may be used for health promotion during pregnancy.
Subject(s)
Attitude to Health , Health Behavior , Pregnancy Complications/prevention & control , Text Messaging , Adult , Breast Feeding , Cohort Studies , Condoms/statistics & numerical data , Female , Humans , Intention , Pregnancy , Prospective Studies , Seat Belts/statistics & numerical data , Smoking/therapy , Smoking Cessation , Vitamins/therapeutic use , Young AdultABSTRACT
Maternal immunization is an effective strategy to prevent and/or minimize the severity of infectious diseases in pregnant women and their infants. Based on the success of vaccination programs to prevent maternal and neonatal tetanus, maternal immunization has been well received in the United States and globally as a promising strategy for the prevention of other vaccine-preventable diseases that threaten pregnant women and infants, such as influenza and pertussis. Given the promise for reducing the burden of infectious conditions of perinatal significance through the development of vaccines against relevant pathogens, the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) sponsored a series of meetings to foster progress toward clinical development of vaccines for use in pregnancy. A multidisciplinary group of stakeholders convened at the NIH in December 2013 to identify potential barriers and opportunities for scientific advancement in maternal immunization.
Subject(s)
Communicable Disease Control , Immunization , Pregnancy Complications, Infectious/prevention & control , Vaccines , Clinical Trials as Topic , Female , Humans , Immunity, Maternally-Acquired , Immunization Programs , Infant , Influenza Vaccines , Influenza, Human/prevention & control , Pregnancy , Tetanus/prevention & control , United States , Vaccines/administration & dosage , Vaccines/adverse effects , Vaccines/immunology , Whooping Cough/prevention & controlABSTRACT
OBJECTIVE: To estimate patients' perceptions of the need, safety and acceptability of vaccination during pregnancy. STUDY DESIGN: An office-based survey was offered to patients presenting for obstetric and gynecologic care from December 2007 to July 2008 at an academic women's hospital. The anonymous questionnaire assessed demographics, medical and vaccination history, interest in receiving vaccines, and beliefs about vaccination safety. Data were evaluated using descriptive statistics and chi2 analyses. RESULTS: A total of 1,436 completed surveys were available for analysis, including 573 from pregnant women. Pregnant women were less likely than non-pregnant women to report perceived risks from vaccine-preventable illness (22.8% vs. 34.5%, p < 0.001) and to believe that their doctor thinks they should get vaccines (42.6% vs. 49.7%, p < 0.027). Nearly two-thirds (61%) reported concern about possible vaccine effects on their pregnancy. However, the overwhelming majority (89%) of pregnant women surveyed reported willingness to accept vaccination during pregnancy if recommended by their obstetrician. CONCLUSION: Despite concerns about vaccine safety and a low perceived need for immunization, most pregnant respondents endorse acceptance of vaccination when recommended by their obstetrician. These findings suggest that obstetric providers should maximize opportunities for uptake of appropriate immunizations during pregnancy.
Subject(s)
Health Knowledge, Attitudes, Practice , Vaccination/psychology , Adolescent , Adult , Female , Humans , Middle Aged , Physician's Role , Pregnancy , Risk Factors , Surveys and Questionnaires , Vaccination/adverse effects , Young AdultABSTRACT
The immune response to COVID-19 booster vaccinations during pregnancy for mothers and their newborns and the functional response of vaccine-induced antibodies against Omicron variants are not well characterized. We conducted a prospective, multicenter cohort study of participants vaccinated during pregnancy with primary or booster mRNA COVID-19 vaccines from July 2021 to January 2022 at 9 academic sites. We determined SARS-CoV-2 binding and live virus and pseudovirus neutralizing antibody (nAb) titers pre- and post-vaccination, and at delivery for both maternal and infant participants. Immune responses to ancestral and Omicron BA.1 SARS-CoV-2 strains were compared between primary and booster vaccine recipients in maternal sera at delivery and in cord blood, after adjusting for days since last vaccination. A total of 240 participants received either Pfizer or Moderna mRNA vaccine during pregnancy (primary 2-dose series: 167; booster dose: 73). Booster vaccination resulted in significantly higher binding and nAb titers, including to the Omicron BA.1 variant, in maternal serum at delivery and in cord blood compared to a primary 2-dose series (range 0.44-0.88 log10 higher, p < 0.0001 for all comparisons). Live virus nAb to Omicron BA.1 were present at delivery in 9 % (GMT ID50 12.7) of Pfizer and 22 % (GMT ID50 14.7) of Moderna primary series recipients, and in 73 % (GMT ID50 60.2) of mRNA boosted participants (p < 0.0001), although titers were significantly lower than to the D614G strain. Transplacental antibody transfer was efficient for all regimens with median transfer ratio range: 1.55-1.77 for IgG, 1.00-1.78 for live virus nAb and 1.79-2.36 for pseudovirus nAb. COVID-19 mRNA vaccination during pregnancy elicited robust immune responses in mothers and efficient transplacental antibody transfer to the newborn. A booster dose during pregnancy significantly increased maternal and cord blood binding and neutralizing antibody levels, including against Omicron BA.1. Findings support the use of a booster dose of COVID-19 vaccine during pregnancy.
Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Infant, Newborn , Female , Pregnancy , Humans , Antibodies, Neutralizing , COVID-19 Vaccines , Cohort Studies , Prospective Studies , COVID-19/prevention & control , SARS-CoV-2 , Antibodies, Blocking , Antibodies, Viral , Vaccination , Pregnancy Complications, Infectious/prevention & controlABSTRACT
Seasonal influenza imparts disproportionate morbidity and death to pregnant women. Immunization against influenza is the most effective intervention to mitigate the burden of influenza disease during pregnancy; nevertheless, immunization rates remain suboptimal in this patient population. Therefore, there is a clear need for strategies to optimize influenza vaccination among pregnant women. We reviewed potential patient and health care provider barriers to influenza immunization and propose effective strategies for overcoming them.
Subject(s)
Health Services Accessibility , Influenza, Human/prevention & control , Patient Acceptance of Health Care , Practice Patterns, Physicians' , Pregnancy Complications, Infectious/prevention & control , Prenatal Care , Vaccination , Directive Counseling , Female , Guideline Adherence , Health Promotion , Humans , Influenza Vaccines/administration & dosage , Influenza Vaccines/adverse effects , Practice Guidelines as Topic , Pregnancy , United StatesABSTRACT
Influenza infection during pregnancy imparts disproportionate morbidity and mortality. This has been primarily noted during occasional influenza pandemics but also during seasonal epidemics. The majority of pregnant women who contract influenza appear to have a mild, self-limited course. However, influenza produces a severe life-threatening respiratory illness among a non-negligible and partially unpredictable portion of susceptible pregnant women. Influenza vaccination is the most effective way to prevent this occasionally fatal infection and is recommended for all pregnant women lacking contraindication. Antiviral medications are indicated for both prophylaxis and treatment for suspected and/or confirmed influenza infection during pregnancy.
Subject(s)
Influenza, Human/diagnosis , Influenza, Human/therapy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/therapy , Antiviral Agents/therapeutic use , Female , Humans , Influenza Vaccines , Influenza, Human/mortality , Influenza, Human/prevention & control , Pregnancy , Pregnancy Complications, Infectious/mortality , Pregnancy Complications, Infectious/virology , Premature Birth/virologyABSTRACT
We sought to delineate the pharmacokinetics (PK) of oseltamivir and its active metabolite oseltamivir carboxylate during pregnancy. Physiologic changes of pregnancy, including increased renal filtration and secretion, may increase the clearance of oseltamivir carboxylate. Sixteen pregnant women taking oseltamivir for prophylaxis or treatment of suspected/proven influenza infection were enrolled. Twenty-three nonpregnant reproductive-age females served as the control group. The primary PK endpoint was area under the plasma concentration time curve for oseltamivir carboxylate. Pregnancy did not alter the PK parameters of the parent compound, oseltamivir. However, for oseltamivir carboxylate the area under the plasma concentration time curve was significantly lower (P = .007) and the apparent clearance significantly higher (P = .006) in pregnant women compared with nonpregnant women. Pregnancy produces lower systemic levels of oseltamivir carboxylate. Increasing the dose and/or dosing frequency of oseltamivir during pregnancy may be necessary to achieve comparable exposure in pregnant and nonpregnant women.
Subject(s)
Antiviral Agents/pharmacokinetics , Influenza, Human/drug therapy , Oseltamivir/pharmacokinetics , Pregnancy Complications, Infectious/drug therapy , Pregnancy/physiology , Adolescent , Adult , Antibiotic Prophylaxis , Antiviral Agents/therapeutic use , Area Under Curve , Case-Control Studies , Female , Humans , Influenza, Human/blood , Metabolic Clearance Rate , Oseltamivir/analogs & derivatives , Oseltamivir/blood , Oseltamivir/therapeutic use , Pregnancy/blood , Pregnancy Complications, Infectious/blood , Young AdultABSTRACT
PURPOSE OF REVIEW: Methicillin-resistant Staphylococcus aureus (MRSA) has become an increasingly aggressive and prevalent pathogen in medicine. This pattern has also been noted in obstetrics. This review will delineate the epidemiology and clinical implications of MRSA during pregnancy. RECENT FINDINGS: Investigations have focused on prevalence of MRSA colonization in obstetrics and the associated morbidity. In addition, some attention has been focused on the neonatal implications of maternal colonization. Overall, the rates of maternal MRSA colonization noted in the United States have been low, in the range of 0.5-4%. The clinical impact of MRSA colonization among pregnant women has also been estimated to be modest. Roughly 357 invasive MRSA infections per 100,000 live births in the United States occur on an annual basis. It is however important to note that published estimates likely underestimate the full scope of MRSA in pregnancy given the lack of formal reporting, importance of related neonatal colonization and morbidity, the complicated treatment implications in pregnant women, the recognized high pathogenicity of MRSA infections, and propensity for recurrent infections among community-acquired MRSA strains. SUMMARY: MRSA is an increasingly important pathogen in modern healthcare and in the obstetric population. Continued surveillance and research remains a top priority.