Pertussis Infections Among Pregnant Women in the United States, 2012-2017.

BACKGROUND: Little is known about pertussis among pregnant women, a population at increased risk for severe morbidity from respiratory infections such as influenza. We used the Centers for Disease Control and Prevention's Enhanced Pertussis Surveillance (EPS) system to describe pertussis epidemiology among pregnant and nonpregnant women of childbearing age. METHODS: Pertussis cases in women aged 18-44 years with cough onset between 1 January 2012 and 31 December 2017 were identified in 7 EPS states. Surveillance data were collected through patient and provider interviews and immunization registries. Bridged-race, intercensal population data and live birth estimates were used as denominators. RESULTS: We identified 1582 pertussis cases among women aged 18-44 years; 5.1% (76/1499) of patients with a known pregnancy status were pregnant at cough onset. Of the pregnant patients with complete information, 81.7% (49/60) reported onset during the second or third trimester. The median ages of pregnant and nonpregnant patients were 29.0 and 33.0 years, respectively. Most pregnant and nonpregnant patients were White (78.3% vs. 86.4%, respectively; P = .09) and non-Hispanic (72.6% vs. 77.3%, respectively; P = .35). The average annual incidence of pertussis was 7.7/100000 among pregnancy women and 7/3/100000 among nonpregnant women. Compared to nonpregnant patients, more pregnant patients reported whoop (41.9% vs. 31.3%, respectively), posttussive vomiting (58.1% vs. 47.9%, respectively), and apnea (37.3% vs. 29.0%, respectively); however, these differences were not statistically significant (P values > .05 for all). A similar proportion of pregnant and nonpregnant patients reported ever having received Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine; 31.6% vs. 32.7%, respectively; P = .84). CONCLUSIONS: Our analysis suggests that incidence of pertussis and clinical characteristics of disease are similar among pregnant and nonpregnant women. Continued monitoring is important to further define pertussis epidemiology in pregnant women.

Tetanus, diphtheria and acellular pertussis (Tdap) vaccine for prevention of pertussis among adults aged 19 years and older in the United States: A cost-effectiveness analysis.

Currently, the Advisory Committee on Immunization Practices recommends one-time tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination for all adults 19 years and older. This study is designed to evaluate the cost-effectiveness of Tdap vaccination for Tdap-eligible adults aged 19 through 85 in the United States. A cost-effectiveness model was developed to compute costs and health outcomes associated with pertussis among 100,000 Tdap-eligible persons of each age cohort. From the societal perspective, the cost per quality-adjusted life-year (QALY) saved was evaluated under the vaccination scenarios. Sensitivity analyses were also conducted to evaluate the impacts of changes in key variables. All costs were adjusted to 2018 US$ with an annual discount rate of 3% applied to costs and outcomes. The incremental cost-effectiveness ratios (ICERs) for vaccinating US adults aged 19 to 85 with Tdap ranged from $248,000/QALY to $900,000/QALY. The lowest cost per QALY was found to be $248,000 for the age 65 cohort, followed by $332,000 for the cohort of age 19, and followed by $477,000 for the age 50 cohort. Sensitivity analysis showed the most dramatic changes in ICER occurred when changing the underreporting factor, vaccine effectiveness and vaccination costs. While Tdap vaccination may not be as cost effective as predicted earlier, it remains the best available preventive measure against pertussis. Further investigation of the true burden of pertussis disease among adults and the effectiveness of Tdap vaccination in this population is needed to better estimate the impact of Tdap vaccination.

Trends in Pertussis Diagnostic Testing in the United States, 1990 to 2012.

BACKGROUND: Reports of pertussis have been increasing in the US since the 1990s, and pertussis diagnostics have evolved during that time. Here, we describe temporal changes in pertussis diagnostic practices in the US during 1990 to 2012 and discuss potential implications. METHODS: Pertussis cases reported through the National Notifiable Diseases Surveillance System during 1990 to 2012 were included in this analysis. Laboratory results were stratified by test type, case classification, age group and case-patient state of residence. RESULTS: This analysis included 291,290 cases with 64% (n = 186,766) reporting at least 1 pertussis laboratory result. Culture and direct fluorescent antibody were the primary results reported during the early 1990s; however, polymerase chain reaction (PCR) surpassed all other test types during the late 1990s and 2000s. By 2012, more than 91% of cases with known results were tested using PCR, either alone or in combination with another test type. Before 2005, Massachusetts reported 71% of serology results, but an increasing number of states reported serologic results during 2005 to 2012. When stratified by age group, overall testing trends persist. As of 2012, culture confirmation is used infrequently across all ages, whereas the use of serology increases with age and is most prevalent among adults aged ≥ 20 years. CONCLUSIONS: PCR has become the primary diagnostic method, and serologic assays now are used in a majority of states. Epidemiologic trends must be considered in the context of changing diagnostic tests, and modifications to surveillance case definitions should be considered to better reflect current testing practices.

Evaluation of Level of Agreement in Bordetella Species Identification in Three U.S. Laboratories during a Period of Increased Pertussis.

While PCR is the most common method used for detecting Bordetella pertussis in the United States, most laboratories use insertion sequence 481 (IS481), which is not specific for B. pertussis; therefore, the relative contribution of other Bordetella species is not understood. The objectives of this study were to evaluate the proportion of other Bordetella species misidentified as B. pertussis during a period of increased pertussis incidence, determine the level of agreement in Bordetella species detection between U.S. commercial laboratories and the CDC, and assess the relative diagnostic sensitivity of CDC's PCR assay when using a different PCR master mix. Specimens collected between May 2012 and May 2013 were tested at two U.S. commercial laboratories for B. pertussis and B. parapertussis detection. Every fifth specimen positive for IS481 and/or IS1001 with cycle threshold (CT) values of ≤35 was sent to CDC for PCR testing that identifies Bordetella species. Specimens with indeterminate or negative results in the CDC PCR were tested using an alternate PCR master mix. Of 755 specimens, there was agreement in species identification for 83.4% (n = 630). Of the specimens with different identifications (n = 125), 79.2% (n = 99) were identified as indeterminate B. pertussis at CDC. Overall, 0.66% (n = 5) of the specimens were identified as B. holmesii or B. bronchiseptica at CDC. Of 115 specimens with indeterminate or negative results, 46.1% (n = 53) were B. pertussis positive when tested by an alternate master mix, suggesting a possible increase in assay sensitivity. This study demonstrates good agreement between the two U.S. commercial laboratories and CDC and little misidentification of Bordetella species during the 2012 U.S. epidemic.

Pertussis Pseudo-outbreak linked to specimens contaminated by Bordetella pertussis DNA From clinic surfaces.

BACKGROUND AND OBJECTIVES: We investigated a pertussis outbreak characterized by atypical cases, confirmed by polymerase chain reaction (PCR) alone at a single laboratory, which persisted despite high vaccine coverage and routine control measures. We aimed to determine whether Bordetella pertussis was the causative agent and advise on control interventions. METHODS: We conducted case ascertainment, confirmatory testing for pertussis and other pathogens, and an assessment for possible sources of specimen contamination, including a survey of clinic practices, sampling clinics for B pertussis DNA, and review of laboratory quality indicators. RESULTS: Between November 28, 2008, and September 4, 2009, 125 cases were reported, of which 92 (74%) were PCR positive. Cases occurring after April 2009 (n = 79; 63%) had fewer classic pertussis symptoms (63% vs 98%; P < .01), smaller amounts of B pertussis DNA (mean PCR cycle threshold value: 40.9 vs 33.1; P < .01), and a greater proportion of PCR-positive results (34% vs 6%; P < .01). Cultures and serology for B pertussis were negative. Other common respiratory pathogens were detected. We identified factors that likely resulted in specimen contamination at the point of collection: environmentally present B pertussis DNA in clinics from vaccine, clinic standard specimen collection practices, use of liquid transport medium, and lack of clinically relevant PCR cutoffs. CONCLUSIONS: A summer pertussis pseudo-outbreak, multifactorial in cause, likely occurred. Recommendations beyond standard practice were made to providers on specimen collection and environmental cleaning, and to laboratories on standardizing PCR protocols and reporting results, to minimize false-positive results from contaminated clinical specimens.

Effects of subretinal electrical stimulation in mer-KO mice.

PURPOSE: Subretinal electrical stimulation (SES) from microphotodiode arrays protects photoreceptors in the RCS rat model of retinitis pigmentosa. The authors examined whether mer(kd) mice, which share a Mertk mutation with RCS rats, showed similar neuroprotective effects from SES. METHODS: Mer(kd) mice were implanted with a microphotodiode array at postnatal day (P) 14. Weekly electroretinograms (ERGs) followed by retinal histology at week 4 were compared with those of age-matched controls. RT-PCR for fibroblast growth factor beta (Fgf2), ciliary nerve trophic factor (Cntf), glial-derived neurotrophic factor (Gdnf), insulin growth factor 1 (Igf1), and glial fibrillary acidic protein (Gfap) was performed on retinas at 1 week after surgery. Rates of degeneration using ERG parameters were compared between mer(kd) mice and RCS rats from P28 to P42. RESULTS: SES-treated mer(kd) mice showed no differences in ERG a- and b-wave amplitudes or photoreceptor numbers compared with controls. However, the expression of Fgf2 and Cntf was greater (6.5 ± 1.9- and 2.5 ± 0.5-fold, respectively; P < 0.02) in SES-treated mer(kd) retinas. Rates of degeneration were faster for dark-adapted maximal b-wave, log σ, and oscillatory potentials in mer(kd) mice than in RCS rats. CONCLUSIONS: Although SES upregulated Fgf2 in mer(kd) retinas, as reported previously for RCS retinas, this was not accompanied by neuroprotection of photoreceptors. Comparisons of ERG responses from mer(kd) mice and RCS rats across different ages showed inner retinal dysfunction in mer(kd) mice but not in RCS rats. This inner retinal dysfunction and the faster rate of degeneration in mer(kd) mice may produce a retinal environment that is not responsive to neuroprotection from SES.

Retinal function and structure in Ant1-deficient mice.

PURPOSE: Mutations in ANT, a mitochondrial ATP transporter, are typically associated with myopathy. Because of the high metabolic demands of the retina, the authors examined whether elimination of the Ant1 isoform in a transgenic mouse affects retinal function or morphology. METHODS: RT-PCR was used to confirm Ant1 expression in retinas of wild-type (WT) or Ant1(-/-) mice. Full-field ERGs were used to test retinal function under dark- and light-adapted conditions and the recovery of the photoresponse to a bright flash. Using histologic methods, the authors assessed the retinal location of ANT and ANT1-ß-gal reporter protein, mitochondrial activity with cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) staining, retinal layer thickness, and bipolar cell types using Chx10 and recoverin. RESULTS: Ant1(-/-) mice had supernormal ERG b-waves under both dark- and light-adapted conditions. X-Gal staining was detected in a subset of cells within the inner retina. The following characteristics were normal in Ant1(-/-) mice compared with age-matched WT mice: recovery of the photoresponse, COX and SDH activity, retinal morphology, and bipolar cell morphology. CONCLUSIONS: The presence of ANT1 in a subset of inner retinal cells accompanied by supernormal ERG responses suggests that ANT1 may be localized to hyperpolarizing bipolar cells. However, the immunohistochemical techniques used here did not show any differences in bipolar cells. Moderate functional changes coupled with a lack of detectable morphologic changes suggest that ANT1 is not essential for ATP transport in the retina.

Tauroursodeoxycholic acid preservation of photoreceptor structure and function in the rd10 mouse through postnatal day 30.

PURPOSE: Retinitis pigmentosa (RP) is a progressive neurodegenerative disease resulting in blindness for which there is no current treatment. Although the members of the family of RP diseases differ in etiology, their outcomes are the same: apoptosis of rods and then by cones. Recently, the bile acid tauroursodeoxycholic acid (TUDCA) has been shown to have antiapoptotic properties in neurodegenerative diseases, including those of the retina. In this study the authors examined the efficacy of TUDCA on preserving rod and cone function and morphology at postnatal day 30 (P30) in the rd10 mouse, a model of RP. METHODS: Wild-type C57BL/6J and rd10 mice were systemically injected with TUDCA (500 mg/kg) every 3 days from P6 to P30 and were compared with vehicle (0.15 M NaHCO(3)). At P30, retinal function was measured with electroretinography, and morphologic preservation of the rods and cones was assessed with immunohistochemistry. RESULTS: Dark-adapted electroretinographic (ERG) responses were twofold greater in rd10 mice treated with TUDCA than with vehicle, likewise light-adapted responses were twofold larger in TUDCA-treated mice than in controls at the brightest ERG flash intensities. TUDCA-treated rd10 retinas had fivefold more photoreceptors than vehicle-treated retinas. TUDCA treatments did not alter retinal function or morphology of wild-type mice when administered to age-matched mice. CONCLUSIONS: TUDCA is efficacious and safe in preserving vision in the rd10 mouse model of RP when treated between P6 and P30. At P30, a developmental stage at which nearly all rods are absent in the rd10 mouse model of RP, TUDCA treatment preserved rod and cone function and greatly preserved overall photoreceptor numbers.

High susceptibility to experimental myopia in a mouse model with a retinal on pathway defect.

PURPOSE: Nob mice share the same mutation in the Nyx gene that is found in humans with complete congenital stationary night blindness (CSNB1). Nob mutant mice were studied to determine whether this defect resulted in myopia, as it does in humans. METHODS: Refractive development was measured in unmanipulated wild-type C57BL/6J (WT) and nob mice from 4 to 12 weeks of age by using an infrared photorefractor. The right eye was form deprived by means of a skull-mounted goggling apparatus at 4 weeks of age. Refractive errors were recorded every 2 weeks after goggling. The content of dopamine and the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were measured by HPLC with electrochemical detection (HPLC-ECD) in retinas of nob and WT mice under light- and dark-adapted conditions. RESULTS: The nob mice had greater hyperopic refractive errors than did the WT mice under normal visual conditions, until 12 weeks of age when both strains had similar refractions. At 6 weeks of age, refractions became less hyperopic in the nob mice but continued to become more hyperopic in the WT mice. After 2 weeks of form deprivation (6 weeks of age), the nob mice displayed a significant myopic shift (~4 D) in refractive error relative to the opposite and control eyes, whereas WT mice required 6 weeks of goggling to elicit a similar response. As expected with loss of ON pathway transmission, light exposure did not alter DOPAC levels in the nob mice. However, dopamine and DOPAC levels were significantly lower in the nob mice compared with WT. CONCLUSIONS: Under normal laboratory visual conditions, only minor differences in refractive development were observed between the nob and WT mice. The largest myopic shift in the nob mice resulted after form deprivation, suggesting that visual pathways dependent on nyctalopin and/or abnormally low dopaminergic activity play a role in regulating refractive development. These findings demonstrate an interaction of genetics and environment in refractive development.

Head-mounted goggles for murine form deprivation myopia.

Recently a murine model has been developed for use in form deprivation myopia experiments. Due to the small size of the head and eye, methods to blur visual input to the mouse eye are challenging. Previous methods to induce form deprivation include lid suture and gluing diffuser goggles directly to the fur around the eye. In this paper we describe a new method of goggling using a head pedestal and goggle, which improves compliance and allows for better ocular health. Nob mice, previously shown to be highly susceptible to form deprivation myopia, were used for these experiments. Immediately following baseline refraction using an infrared automated photorefractor, mice were either goggled with a diffuser attached directly to the fur or with a head-mounted goggling apparatus. The goggle apparatus consists of five main components: goggle and frame, head pedestal, acrylic cube for stabilization, and balancing bar. Mice were goggled for 2 weeks in which ocular health and goggle position was monitored and then had a final refraction. The use of head-mounted goggles resulted in 75% fewer instances of goggle loss and 55% fewer ocular complications compared to goggles glued to the fur. Both goggling methods induced a myopic shift of approximately 5 diopters. The head-mounted goggle apparatus provides an improved method for inducing form deprivation in mice and offers the ability to easily take repeated refractive measurements as well as allowing for the use of defocusing lenses.

Status of the feline retina 5 years after subretinal implantation.

Retinal prosthetics are designed to restore functional vision to patients with photoreceptor degeneration by detecting light and stimulating the retina. Since devices are surgically implanted into the eye, long-term biocompatibility and durability are critical for viable treatment of retinal disease. To extend our previous work, which demonstrated the biocompatibility of a microphotodiode array (MPA) for 10 to 27 months in the normal feline retina, we implanted normal cats with an MPA implant backed with either an iridium oxide or platinum electrode and examined retinal function and biocompatibility for 3 to 5 years. All implants functioned throughout the study period. Retinal function remained steady and normal with a less than 15 percent decrease in electroretinogram response. The retinas had normal laminar structure with no signs of inflammation or rejection in areas adjacent to or distant from the implants. Directly over the implants, a loss of photoreceptor nuclei and remodeling of inner retinal layers existed. These results indicate that the subretinal MPA device is durable and well tolerated by the retina 5 years postimplantation.