Understanding Trends in Pertussis Incidence: An Agent-Based Model Approach

Erinn Sanstead, MPH; Cynthia Kenyon, MPH; Seth Rowley, MPH; Eva Enns, PhD; Claudia Miller, MS; Kristen Ehresmann, RN, MPH; Shalini Kulasingam, PhD

Disclosures

Am J Public Health. 2015;105(9):e42-47. 

In This Article

Abstract and Introduction

Abstract

Objectives. We examined the impact of undetected infections, adult immunity, and waning vaccine-acquired immunity on recent age-related trends in pertussis incidence.

Methods. We developed an agent-based model of pertussis transmission in Dakota County, Minnesota using case data from the Minnesota Department of Health. For outbreaks in 2004, 2008, and 2012, we fit our model to incidence in 3 children's age groups relative to adult incidence. We estimated parameters through model calibration.

Results. The duration of vaccine-acquired immunity after completion of the 5-dose vaccination series decreased from 6.6 years in the 2004 model to approximately 3.0 years in the 2008 and 2012 models. Tdap waned after 2.1 years in the 2012 model. A greater percentage of adults were immune in the 2008 model than in the 2004 and 2012 models. On average, only 1 in 10 adult infections was detected, whereas 8 in 10 child infections were detected.

Conclusions. The observed trends in relative pertussis incidence in Dakota County can be attributed in part to fluctuations in adult immunity and waning vaccine-acquired immunity. No single factor accounts for current pertussis trends.

Introduction

The United States is experiencing a resurgence of pertussis despite concerted public health efforts to prevent infection. Outbreaks have gradually increased in size since the late 1970s, with substantial increases occurring during the past decade.[1,2] National incidence rates have remained highest among infants younger than 1 year, but the remaining burden of disease has shifted between age groups.[2] The average age of someone with pertussis before the vaccine era was 5 years. Recently, outbreaks have been recorded with an increased percentage of cases in those older than 5 years. In particular, children aged 7 to 10 years have recently begun to experience a greater burden of disease than have other age groups.[2,3]

Similar to national trends, in Minnesota changes in pertussis burden by age have been observed despite relatively consistent overall vaccination rates.[4] In 2004, children (5–12 years) accounted for 28% of reported pertussis cases, adolescents (13–17 years) accounted for 35% of cases, and adults (≥ 18 years) accounted for 25% of cases. During Minnesota's subsequent peak year of 2008, 42% of cases were in children, 23% of cases were in adolescents, and 23% of cases were in adults. Incidence rates in all age groups increased from 2004 to 2008. The age distribution of cases in 2012 was nearly identical to that in 2008.[5]

Although protecting the vulnerable infant population remains a public health priority, understanding the driving factors behind incidence trends in older age groups is necessary to develop and implement effective control measures. The transition from a whole cell pertussis vaccine, DTP, to an acellular vaccine, DTaP, in the 1990s appears to have played a role in increasing incidence among those aged 7–10 years.[6] The recommended ages for children to receive DTaP are the same as for DTP (2, 4, 6, and 15–18 months and 4–6 years), but immune protection acquired from DTaP has been reported to wane sooner than that acquired from DTP.[7]

In addition to vaccine changes, improved laboratory testing, increased awareness, and the introduction of a booster for adolescents and adults (Tdap) have played a role in altering incidence trends.[8–10] Research is needed to explain how these factors have collectively contributed to the resurgence of pertussis;[11] however, this research is complicated by uncertainty in other contributing factors that are difficult to assess directly, such as undetected infections, adult immunity, and waning vaccine-acquired immunity.

Adults with pertussis often present with mild symptoms, and a nondistinctive cough may be the only manifestation of infection.[12] Consequently, a large number of adult infections remain undetected.[13] Although adults do not constitute a large percentage of reported cases, their mild and asymptomatic infections are believed to play a significant role in transmission.[14] Among children, mild or asymptomatic infections in previously immunized individuals may similarly remain undetected.[15]

Childhood vaccination records for adults are often incomplete and likely do not represent current immune status because of waning immunity. Records of Tdap vaccination are often the only documentation relevant to current immunity in adults, and these records are more challenging to locate than are records for children.[16] Seroprevalence data have been relied on to generate estimates of infection and immunity within adult populations, but serologic testing is not standardized and antibodies may reach undetectable levels before immunity wanes.[7,17,18]

DTP was used for all pertussis vaccinations before the 1990s and is estimated to provide protection for 4 to 12 years beyond the last dose.[7] DTaP was initially approved in 1991 for administration to children aged 15 months to 6 years who had received a DTP primary series (shots 1, 2, and 3), and in 1997 DTaP was approved for all 5 doses in children.[19] Estimates for the duration of DTaP-induced immunity suggest that protection lasts 5 to 6 years after completion of the DTaP series, with efficacy decreasing each year.[20,21] In 2005, Tdap was licensed as a booster shot for adolescents and adults; the longevity of its protection is still being assessed.

With the relatively new field of agent-based modeling, factors that are difficult to measure directly (undetected infections, adult immunity, and waning immunity) can be investigated with computer simulations that can capture high levels of detail. A variety of software platforms have been developed to support this modeling technique in which individuals, or "agents," in an agent-based model (ABM) move and act independently in a simulated environment on the basis of a set of rules that are determined by their assigned characteristics and model parameters.[22] Each individual is programmed to have characteristics (e.g., age and vaccination status) that mimic an individual in a particular population that reflects a geographic region (e.g., a county or a state). ABMs can thus provide insight into local drivers of pertussis outbreaks.

Using data from the Minnesota Department of Health (MDH), we developed an explanatory ABM of pertussis transmission. We simulated outbreaks that occurred in Dakota County, Minnesota during 2004, 2008, and 2012 (Table 1). Dakota County has a population of approximately 400 000 residents and is relatively ethnically diverse (18% non-White) with a mixture of urban and rural settings (approximately one third each of land use is rural, urban, and suburban).[23] This population was representative of the state with regard to age-related incidence trends. We calibrated the ABM to attain parameter values for undetected infections, adult immunity, and waning vaccine-acquired immunity so that model output was consistent with age-related relative incidence trends observed during the Dakota County outbreaks.

We identified these factors' influence on pertussis's changing incidence trends with an ABM.

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