Infant Pertussis: Is Cocooning the Answer?

E D I T O R I A L C O M M E N TA R Y Infant Pertussis: Is Cocooning the Answer? Flor Munoz1,2 and Janet Englund3,4 1Department of Pediatrics, and 2Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas; 3Department of Pediatrics, Seattle Children's Hospital and University of Washington; and 4Fred Hutchinson Cancer Research Center, Seattle, Washington (See the article by Halperin et al, on pages 885–92.) Infants in North America continue to suffer and die of pertussis today, in the 21st century, despite the availability of safe and effective pertussis vaccines for .60 years (Figure 1). A notable resurgence of pertussis has occurred during the past 25 years in the United States, Canada, and other countries where vaccination coverage is high. Since the introduction and widespread use of childhood vaccines, the epidemiological characteristics of pertussis have changed; more cases now occur in adolescents and adults who are susceptible as a result of waning immunity, because protection following vaccination or natural pertussis infection is not lifelong. These older individuals become reservoirs of disease and a potential source of infection to infants too young to be immunized or protected by vaccine [1]. Currently, infants ,6 months of age have the highest rate of pertussis infection (143 cases per 100 000 population), compared with the total population (6.9 cases per 100 000 population) [2]. Importantly, $90% of pertussis deaths occur in Received 1 July 2011; accepted 12 July 2011. Correspondence: Janet Englund, MD, Section of Infectious Diseases, Seattle Children's Hospital, 4800 Sand Point Way NE MS R5441, Seattle, WA 98105 (). Clinical Infectious Diseases 2011;53(9):893–896 Ó The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: . 1058-4838/2011/539-0006$14.00 DOI: 10.1093/cid/cir542 neonates and infants ,3 months of age (Figures 2 and 3). During the 2010 California outbreak, 9120 cases of pertussis were reported, and 10 infants who acquired the disease during the first 2 months of life died. The outbreak resulted in the highest number of cases reported in California during the vaccine era, with rates similar to those seen in 1947, and the highest incidence in that state since 1958 [3] (Figure 3). Unfortunately, this situation is not unique, because similar outbreaks have been reported during the past decade throughout the United States in Texas, Michigan, Illinois, and Ohio, and pertussis activity remains high in 2011 [4, 5]. Mothers and fathers but also siblings and adult family contacts are responsible for the transmission of pertussis to young infants [6, 7]. Furthermore, casual community contacts have been estimated to account for up to 34% of cases as a source of pertussis infection in infants [8]. In the United States and Canada, the current pertussis prevention strategy consists of a complicated vaccination schedule including a primary series at 2, 4, and 6 months; boosters at 18 months, 4–6 years, and again around 12 years of age; and later adult vaccination. Immunization of adolescents and adults with a single dose of tetanus–diphtheria– acellular pertussis vaccine (Tdap) has been recommended in Canada since 2003 and in the United States since 2005 [9, 10]. Adults who are in contact with infants or other high-risk groups, such as patients, are strongly encouraged to receive Tdap to prevent transmission of pertussis to these vulnerable populations. However, Tdap vaccination coverage in adults remains low in the United States. In 2008, only 5.9% of adults had received a dose of Tdap; coverage among adults with infant contact was estimated to be 5.0%, and only 15.9% among healthcare workers [11]. As rates of infant pertussis escalate, it is clear that the recommended adolescent and adult vaccination schedules have not affected infant morbidity and mortality. Other proposed strategies to prevent infant pertussis infection include neonatal or maternal immunization, and the socalled cocooning strategy—providing indirect protection of infants who are too young to be vaccinated through immunization of household and close contacts, including postpartum women [12]. In this issue of Clinical Infectious Diseases, Halperin et al report the results of 2 well-executed studies designed to address the basic question of whether antibody responses to Tdap in women are sufficiently rapid to support the cocoon strategy [13]. This information is critical for the prevention of pertussis disease through cocooning, because 2–3-month-old infants are the peak group at risk for serious or fatal disease following exposure during the neonatal period, frequently from their own mothers [6, 7]. For postpartum vaccination of mothers to be effective in EDITORIAL COMMENTARY d CID 2011:53 (1 November) d 893 Figure 1. Chest radiograph of 2-month-old infant with pertussis who died after a complicated 1-month-long hospital course including mechanical ventilation and extracorporeal membrane oxygenation treatment. providing indirect protection to infants by preventing maternal infection, mothers should be protected against pertussis shortly after delivery. To determine the rapidity of the immune response, Halperin et al closely followed 30 healthy women of childbearing age and 50 postpartum women after receipt of Tdap (Adacel, Sanofi Pasteur). Prevaccination antibody levels (IgG and IgA) to pertussis, tetanus, and diphtheria antigens were compared with levels in serum samples collected frequently after vaccination in women of childbearing age and in postpartum women. Colostrum/breast milk samples were collected from postpartum women at the same times for measurement of breast milk IgA against pertussis antigens. The investigators’ ability to carry out this unique, thorough, and labor-intensive study design is commendable. This study evaluates for the first time the kinetics of the immediate antibody response to Tdap in women and breast milk antibodies to pertussis vaccine antigens in postpartum women. Tdap elicited an anamnestic response in previously vaccinated women of childbearing age and postpartum women. Although a correlate of immunity is not known for pertussis, a 4-fold increase in Figure 2. Reported pertussis cases and incidence by age group in the United States, 2010 [2]. 894 d CID 2011:53 (1 November) d EDITORIAL COMMENTARY serum IgG antibody titers to pertussis antigens (PT, FHA, PRN, FIM), as well as tetanus and diphtheria, was achieved by 83.3%–100% of study participants, and although serum IgA responses to PT were not as robust in healthy women of childbearing age, a 4-fold increase in antibodies to pertussis antigens was achieved by a high percentage of women (43.6%– 94.9%). Both studies clearly reveal that serum IgG and IgA antibodies are not detectable until 5–7 days after vaccination and that a maximum response is no (...truncated)