Beverly Connelly

Pertussis Vaccine Effectiveness Among Children 6 to 59 Months of Age in the United States, 1998–2001

Background. Despite the dramatic pertussis decrease since the licensure of whole-cell pertussis (diphtheria-tetanus toxoids-pertussis [DTP]) vaccines in the middle 1940s, pertussis remains endemic in the United States and can cause illness among persons at any age; >11000 pertussis cases were reported in 2003. Since July 1996, in addition to 2 DTP vaccines already in use, 5 acellular pertussis (diphtheria-tetanus toxoids-acellular pertussis [DTaP]) vaccines were licensed for use among infants; 3 DTaP vaccines were distributed widely during the study period. Because of the availability of 3 DTaP and 2 DTP vaccines and the likelihood of the vaccines being used interchangeably to vaccinate children with the recommended 5-dose schedule, measuring the effectiveness of the pertussis vaccines was a high priority. Objective. To measure the pertussis vaccine effectiveness (VE) among US children 6 to 59 months of age. Design. We conducted a case-control study in the Cincinnati, Ohio, metropolitan area, Colorado, Idaho, and Minnesota. Participants. Confirmed pertussis cases among children 6 to 59 months of age at the time of disease onset, with onset in 1998–2001, were included. For each case subject, 5 control children were matched from birth certificate records, according to the date of birth and residence. Outcome Measures. A standardized questionnaire was used to obtain vaccination data from parents and providers. Parents/guardians were asked about demographic characteristics, child care attendance, the number of household members who stayed at the same home as the enrolled child for ≥2 nights per week, and cough illness of ≥2-week duration among these household members in the month before the case patients cough onset. Pertussis vaccine doses among case children were counted as valid if they were received ≥14 days before the cough onset date (“valid period”). The age of the case patient (in days) at the end of the valid period was determined, and doses of vaccine for the matched control subjects were counted as valid if they were received by that age. Conditional logistic regression models were used to estimate the matched odds ratios (ORs) for pertussis according to the number of pertussis vaccine doses. The VE was calculated with the following formula: (1 − OR) × 100. Because the pertussis antigen components or amounts differed according to vaccine, the VE of 3 or 4 doses of DTP and/or DTaP was estimated according to the recorded vaccine manufacturer and vaccine type. Results. All enrolled children (184 case subjects and 893 control subjects) had their vaccine history verified. The proportions of children who received 0, 1 or 2, 3, and ≥4 pertussis (DTP and/or DTaP) vaccine doses among case subjects were 26%, 14%, 26%, and 34% and among control subjects were 2%, 8%, 33%, and 57%, respectively. Compared with 0 doses, the unadjusted VE estimate for 1 or 2 pertussis doses was 83.6% (95% confidence interval [CI]: 61.1–93.1%), that for 3 doses was 95.6% (95% CI: 89.7–98.0%), and for ≥4 doses was 97.7% (95% CI: 94.7–99.0%). Among children who received 4 pertussis vaccinations, the risk of pertussis was slightly higher among those who received only 1 type of vaccine (either 4 DTP doses or 4 DTaP doses), compared with those who received a combination of DTP for doses 1 to 3 and DTaP for dose 4 (OR: 2.4; 95% CI: 1.1–5.2). Among children who received 3 or 4 DTaP vaccine doses, the risk of pertussis was slightly higher among those who received a DTaP vaccine with 4 pertussis antigen components (a vaccine no longer available), compared with those who received the DTaP vaccine with 2 pertussis antigen components (OR: 2.5; 95% CI: 1.1–5.8). Among children who received 4 doses, the risk of pertussis was 2.7 times higher for children who received dose 4 early (age of ≤13 months), compared with children who received dose 4 at an older age (age of ≥14 months) (95% CI: 1.1–6.8). For children 6 to 23 months of age, features of household structure were significant risk factors for pertussis. In a multivariate model, compared with living with an older parent (≥25 years of age), not living with an “other” household member (a relative other than a parent or sibling or a nonrelated person), and not living with a sibling 6 to 11 years of age, the risk of pertussis for children 6 to 23 months of age was 6.8 times higher if they lived with a young parent (≤24 years of age) (95% CI: 3.1–15.0), 2.5 times higher if they lived with an “other” household member (95% CI: 1.2–5.4), and 2.2 times higher if they lived with a sibling 6 to 11 years of age (95% CI: 1.2–4.3). Adjusting for these risk factors did not change the VE. Compared with control children, case children were significantly more likely to live with a household member (representing all age groups and relationships) who reported a recent cough illness with duration of ≥2 weeks (87 [52%] of 168 case subjects, compared with 79 [8%] of 860 control subjects). Conclusions. Any combination of ≥3 DTP/DTaP vaccine doses for children 6 to 59 months of age was highly protective against pertussis. However, there were differences according to vaccine type (DTaP or DTP) and DTaP manufacturer. Among children who received 4 pertussis vaccine doses, a combination of 3 DTP doses followed by 1 DTaP dose had a slightly higher VE than other combinations; among children who received 3 or 4 DTaP vaccine doses, 1 DTaP vaccine performed less well. The finding that pertussis dose 4 was more effective when given to children at ≥14 months of age might be confounded if health care providers were more likely to vaccinate children at 12 months of age because of a perceived risk of undervaccination and if these same children were also at higher risk for pertussis. Household members of any age group and relationship could have been the source of pertussis, and household structure was associated with risk for pertussis for children 6 to 23 months of age. In contrast to control children in the study, 26% of case children had never been vaccinated against pertussis. Unvaccinated children are at risk for pertussis and, in a community with other unvaccinated children, can lead to community-wide pertussis outbreaks. Parents need to be educated about the morbidity and mortality risks associated with Bordetella pertussis infection, and they need to be encouraged to vaccinate their children against pertussis on time and with the recommended number of vaccine doses for optimal protection.

A Hospital-wide Quality-Improvement Collaborative to Reduce Catheter-Associated Bloodstream Infections

BACKGROUND: Catheter-associated bloodstream infections (CA BSIs) are associated with increased hospital length of stay, total hospital costs, and mortality. Quality-improvement collaboratives (QICs) are frequently used to improve health care quality. Our PICU was previously involved in a successful national QIC to reduce the incidence of CA BSI in critically ill children. OBJECTIVE: We hypothesized that the formation of a hospital-wide QIC would reduce the incidence of CA BSI throughout our institution. METHODS: We retrospectively reviewed the incidence of CA BSI from March 2006 to March 2010. The collaborative approach included hospital-wide implementation of central-line insertion and maintenance bundles that emphasized full sterile barrier precautions and chlorhexidine skin preparation during line insertion, daily discussion of catheter necessity, and meticulous site and tubing care. The hospital units involved were our 3 critical care units, the oncology unit, the bone marrow transplant unit, and wards. Each individual unit was responsible for collecting unit-specific data and performing event-cause analysis within 48 hours of identifying a CA BSI. These results were shared with the other hospital units during monthly meetings. Compliance with the insertion and maintenance bundles was monitored and reported to each unit monthly. RESULTS: The hospital-wide CA-BSI rate decreased from a baseline of 3.0 to <1.0 CA BSI per 1000 line-days after implementation of the QIC. CONCLUSIONS: Our hospital-wide QIC resulted in a significant reduction in the incidence of CA BSI at our childrens hospital. A collaborative model based on improvement science methodology is both feasible and effective in reducing the incidence of CA BSI.

Sweet's Syndrome as an Initial Manifestation of Pediatric Human Immunodeficiency Virus Infection

We report a 3-month-old infant in whom Sweets syndrome was a presenting manifestation of pediatric human immunodeficiency virus infection. Although rare in children, Sweets syndrome may be associated with certain infections and malignancies. The diagnosis of Sweets syndrome in a child should always prompt a thorough evaluation to assess for an associated systemic disease.

Reducing Surgical Site Infections at a Pediatric Academic Medical Center

BACKGROUND Surgical site infections (SSIs) remain a substantial cause of morbidity, mortality, increased length of stay, and increased hospital costs. Cincinnati Childrens Hospital Medical Center (CCHMC) used reliability science to dramatically reduce the rate of surgical site infections. METHODS Key activities included the development and implementation of strategies to enhance the proportion of patients who receive timely antibiotic administration, a pediatric surgical site infection-prevention bundle, and procedure-specific pediatric surgical site infection-prevention bundles. Measures are presented in monthly reports and annotated control charts that are shared with the improvement team and organizational leadership and that are also posted on the hospitals patient safety intranet site. RESULTS The Class I and II SSI rate decreased from 1.5 per 100 procedure days at baseline to 0.54 per 100 procedure days, a 64% reduction. The process has remained stable (within control limits) since August 2007. There were 33 fewer surgical site infections in fiscal year (FY) 2006 than in FY 2005, and 21 fewer in FY 2007 than in FY 2006. By December 2007, 91% of eligible same-day surgery patients received antibiotics within 60 minutes before a procedure, and 94% of patients undergoing inpatient surgery received antibiotics within 60 minutes prior to incision. DISCUSSION Pediatric surgical patients can now expect a safer, more efficient experience with CCHMCs care system and reduced variation in care across CCHMCs surgeons and procedures. Sharing data on individual and collective provider performance was important in recruiting provider support. Examining data on any failures each day allowed assessment and correction, facilitating rapid-cycle improvement. Making the right thing to do the easy thing to do facilitated the behavior changes required.

Characterization of Serological Responses to Pertussis

ABSTRACT We have compared the use of five nonvaccine antigens to the use of conventional vaccine antigens, pertussis toxin (PT), and filamentous hemagglutinin (FHA) for the serological diagnosis of pertussis by enzyme-linked immunosorbent assay (ELISA). The nonvaccine antigens included the catalytic region of adenylate cyclase toxin (CatACT), the C-terminal region of FHA (C-FHA), lipooligosaccharide (LOS), the peptidoglycan-associated lipoprotein (PAL), and the BrkA protein. The serological responses of individuals with culture-confirmed pertussis were compared to those of adults with no recent history of a coughing disease. An immunoglobulin G (IgG) ELISA for PT was the most sensitive (92.2%) test for the serodiagnosis of pertussis. Of the nonvaccine antigens, ELISA for IgG responses to CatACT (sensitivity, 62.8%), C-FHA (sensitivity, 39.2%), and LOS IgA (sensitivity, 29.4%) were less sensitive but could also distinguish culture-positive individuals from control individuals. The use of a combination of multiple ELISA targets improved the sensitivity of the assay for serological diagnosis. Elevated IgG and IgA antibody titers persisted for more than a year in the individuals with culture-confirmed pertussis.

Phagocytosis of Bordetella pertussis Incubated with Convalescent Serum

Convalescent serum samples were examined for the ability to promote phagocytosis of Bordetella pertussis by human neutrophils. One sample promoted phagocytosis, and 11 of the 51 samples caused a statistically significant reduction in phagocytosis, compared with that of bacteria not incubated with serum. Phagocytosis was influenced by interactions between antibodies that promoted phagocytosis and antibodies that inhibited phagocytosis. Adenylate cyclase toxin (ACT) has been shown to block phagocytosis by neutrophils. Antibodies to ACT were removed from the sample that promoted phagocytosis, by incubation with ACT-coated paramagnetic beads, and the depleted serum no longer enhanced phagocytosis. The adhesin filamentous hemagglutinin (FHA) has been shown to mediate attachment of B. pertussis to neutrophils in a way that promotes phagocytosis. Depletion of antibodies to FHA from samples that blocked phagocytosis improved phagocytosis, compared with the no-antibody control. These results suggest that antibodies to ACT can promote phagocytosis, whereas antibodies to FHA can counteract beneficial opsonins.

Utilizing improvement science methods to improve physician compliance with proper hand hygiene

OBJECTIVE: In 2009, The Joint Commission challenged hospitals to reduce the risk of health care–associated infections through hand hygiene compliance. At our hospital, physicians had lower compliance rates than other health care workers, just 68% on general pediatric units. We used improvement methods and reliability science to increase compliance with proper hand hygiene to >95% by inpatient general pediatric teams. METHODS: Strategies to improve hand hygiene were tested through multiple plan-do-study-act cycles, first by 1 general inpatient medical team and then spread to 4 additional teams. At the start of each rotation, residents completed an educational module and posttest about proper hand hygiene. Team compliance data were displayed daily in the resident conference room. Real-time identification and mitigation of failures by a hand-washing champion encouraged shared accountability. Organizational support ensured access to adequate hand hygiene supplies. The main outcome measure was percent compliance with acceptable hand hygiene, defined as use of an alcohol-based product or hand-washing with soap and turning off the faucet without using fingers or palm. Compliance was defined as acceptable hand hygiene before and after contact with the patient or care environment. Covert bedside observers recorded at least 8 observations of physicians’ compliance per day. RESULTS: Physician compliance with proper hand hygiene improved to >95% within 6 months and was sustained for 11 months. CONCLUSIONS: Instituting a hand-washing champion for immediate identification and mitigation of failures was key in sustaining results. Improving physician compliance with proper hand hygiene is achievable and a first step in decreasing health care–associated infections.

Controversies in Vaccine Mandates

Policies that mandate immunization have always been controversial. The controversies take different forms in different contexts. For routine childhood immunizations, many parents have fears about both short- and long-term side effects. Parental worries change as the rate of vaccination in the community changes. When most children are vaccinated, parents worry more about side effects than they do about disease. Because of these worries, immunization rates go down. As immunization rates go down, disease rates go up, and parents worry less about side effects of vaccination and more about the complications of the diseases. Immunization rates then go up. For teenagers, controversies arise about the criteria that should guide policies that mandate, rather than merely recommend and encourage, certain immunizations. In particular, policy makers have questioned whether immunizations for human papillomavirus, or other diseases that are not contagious, should be required. For healthcare workers, debates have focused on the strength of institutional mandates. For years, experts have recommended that all healthcare workers be immunized against influenza. Immunizations for other infections including pertussis, measles, mumps, and hepatitis are encouraged but few hospitals have mandated such immunizations-instead, they rely on incentives and education. Pandemics present a different set of problems as people demand vaccines that are in short supply. These issues erupt into controversy on a regular basis. Physicians and policy makers must respond both in their individual practices and as advisory experts to national and state agencies. The articles in this volume will discuss the evolution of national immunization programs in these various settings. We will critically examine the role of vaccine mandates. We will discuss ways that practitioners and public health officials should deal with vaccine refusal. We will contrast responses of the population as a whole, within the healthcare setting, and in the setting of pandemic influenza.

Estimating the Rotavirus Hospitalization Disease Burden and Trends, Using Capture-recapture Methods

Background: Rotavirus surveillance is needed to provide estimates of disease burden and to evaluate the effect of vaccination programs. Our objective was to use capture-recapture methods to estimate rotavirus hospitalization rates and to examine trends over time. Methods: Children <3 years of age residing in Hamilton County, Ohio hospitalized with acute gastroenteritis, and laboratory-confirmed rotavirus between 1997 and 2008 were identified through 2 independent surveillance systems: an active system with prospective enrollment of children admitted with acute gastroenteritis and a passive system of children identified by rotavirus testing as part of their usual medical care. Capture-recapture methods compared cases from both systems to estimate the number of missed cases from either system. Using census data for Hamilton County, rates per 10,000 with 95% confidence intervals (CI) for rotavirus hospitalizations were estimated. Results: Overall, 486 cases were identified using active surveillance and 244 using passive surveillance, with 127 cases captured by both. Using capture-recapture methods, the overall rate in children <3 years old was 26.9/10,000; CI: 24.1, 30.6. Rates varied by year: highest in 1998 (48.1/10,000; CI: 32.4, 92.2) and lowest in 2008 (3.2/10,000; CI: 2.1, 6.1) after rotavirus vaccine introduction. Among children <5 years old, rates were highest in <3-month-old children (51.8/10,000; CI: 39.4, 75.1) and lowest in older age groups: 24 to 35 months (20.5/10,000; CI: 14.7, 30.3) and 36 to 59 months (4.1/10,000; CI: 2.9, 7.2). Rates from capture-recapture methods and adjusted active system were comparable. Conclusions: Capture-recapture methods were a useful tool to estimate rotavirus disease burden and to monitor trends, especially in the era of rotavirus immunization.

Quality-Improvement Initiative Sustains Improvement in Pediatric Health Care Worker Hand Hygiene

OBJECTIVE: To use quality-improvement (QI) methods to develop and test a multimodal intervention to improve hand-hygiene compliance among health care workers (HCWs) to >90%. METHODS: We used a quasi-experimental staggered intervention that was conducted on 2 similar general pediatric units within a 475-bed tertiary childrens hospital. Compliance was defined as acceptable hand hygiene both before and after contact with the patient or the patients care environment. Measurement of HCW hand-hygiene compliance was performed by covert observations made during routine patient care. Twelve months of preintervention data were collected. QI methods were used to test and implement interventions sequentially in each unit. Interventions addressed leadership support, improving HCW knowledge, hand-hygiene supply availability, and HCW behavior. RESULTS: Interventions began on unit A on November 10, 2008. Similar interventions were later tested on unit B starting March 23, 2009. By April 1, 2009, compliance increased on unit A (from 65% to 91%) and unit B (from 74% to 92%). Improvement on each unit occurred only after the interventions were introduced. Identifying HCWs who failed to perform hand hygiene and offering alcohol-based hand rub to them before patient contact resulted in the greatest improvement. Improvements were sustained on both units for 18 months. CONCLUSIONS: Use of QI methods to implement a multimodal intervention resulted in sustained improvement in hand-hygiene compliance. Real-time individual performance feedback or other high-reliability human-factor interventions seem to be necessary to reach and sustain high levels of hand-hygiene compliance.