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NEW THIS SUNDAY: PERTUSSIS EPIDEMIOLOGY WORLDWIDE AND IN ITALY

Saturday, 13th of July 2013

• PERTUSSIS: A REVIEW OF DISEASE EPIDEMIOLOGY WORLDWIDE AND IN ITALY

Int J Environ Res Public Health. 2012 Dec;9(12):4626-38.

Gabutti G, Rota MC.

Source

LHU 4 Chiavarese, Hygiene and Public Health O.U., Corso Dante, Chiavari, Ge, Italy. ggabutti@asl4.liguria.it

Abstract below; full text is at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546780/

Pertussis continues to be a relevant public-health issue. The high coverage rates achieved have decreased the spread of the pathogen, but the waning of immunity implies a relevant role of adolescents and adults in the infective dynamics as they may represent a significant source of infection for unvaccinated or incompletely immunized newborns. The passive surveillance system is affected by many limitations. The underestimation of pertussis in adolescents, young adults and adults is mainly related to the atypical clinical characteristics of cases and the lack of lab confirmation. The real epidemiological impact of pertussis is not always perceived, anyway, the unavailability of comprehensive data should not hamper the adoption of active prophylactic interventions aimed at preventing the impact of waning immunity on pertussis. To avoid an increase of the mean age of acquisition of the infection, a booster dose of low-antigen content combined vaccine should be adopted in adolescents and adults. A decreased risk of infection in newborns can be achieved with the cocoon strategy, although the debate on this aspect is still open and enhanced surveillance and further studies are needed to fine-tune the pertussis prevention strategy.

E� et�� pZ pertussis) is the causative agent of whooping cough, which is a highly contagious disease in the human respiratory tract. Despite vaccination since the 1950s, pertussis remains the most prevalent vaccine-preventable disease in developed countries. A recent resurgence pertussis is associated with the expansion of B. pertussis strains with a novel allele for the pertussis toxin (ptx) promoter ptxP3 in place of resident ptxP1 strains. The recent expansion of ptxP3 strains suggests that these strains carry mutations that have increased their fitness. Compared to the ptxP1 strains, ptxP3 strains produce more Ptx, which results in increased virulence and immune suppression. In this study, we investigated the contribution of gene expression changes of various genes on the increased fitness of the ptxP3 strains. Using genome-wide gene expression profiling, we show that several virulence genes had higher expression levels in the ptxP3 strains compared to the ptxP1 strains. We provide the first evidence that wildtype ptxP3 strains are better colonizers in an intranasal mouse infection model. This study shows that the ptxP3 mutation and the genetic background of ptxP3 strains affect fitness by contributing to the ability to colonize in a mouse infection model. These results show that the genetic background of ptxP3 strains with a higher expression of virulence genes contribute to increased fitness.

 

aggre�y�� pZver the past 30 y. To dissect the contributions of waning pertussis immunity and repeat infections to pertussis epidemiology in Thailand following a pronounced increase in vaccine uptake, we used likelihood-based statistical inference methods to evaluate the support for multiple competing transmission models. We found that, in contrast to other settings, there is no evidence for pertussis resurgence in Thailand, with each model examined pointing to a substantial rise in herd immunity over the past 30 y. Using a variety of empirical metrics, we verified our findings by documenting signatures of changing herd immunity over the study period. Importantly, this work leads to the conclusion that repeat infections have played little role in shaping pertussis epidemiology in Thailand. Our results are surprisingly emphatic in support of measurable impact of herd immunity given the uncertainty associated with pertussis epidemiology.

 

Pertussis, or whooping cough, was historically considered a serious disease of childhood. Because of the high burden of morbidity and mortality associated with pertussis (1), routine vaccination programs were implemented in many developed countries during the 1940s and 1950s that led, in some instances, to a 99% reduction in reported incidence (2, 3). The success of these vaccination programs in reducing pertussis notifications led to optimism over its potential eradication, a sentiment that has since been replaced by widespread concern following high-profile outbreaks in populations with long-standing immunization, with the United States and Australia arguably experiencing the largest impacts of these resurgences (4⇓⇓–7).

Recent attempts to explain contemporary pertussis epidemiology have largely attributed the resurgence to the immunological consequences of vaccination and natural infection. In turn, uncertainty surrounding the role of a number of potentially key players has been highlighted, including the duration of naturally acquired and vaccine-induced immunity (8⇓⇓–11), limited natural immune boosting following the introduction of vaccine programs (10, 12), loss of vaccine efficacy resulting from antigenic divergence (13, 14), and, crucially, whether vaccines prevent pertussis transmission or simply reduce the incidence of disease (15⇓–17). To assess the population-level consequences of immunity, we confront high-resolution incidence reports in Thailand with modern techniques for statistical inference to provide a mechanistic interpretation of the transmission impact of vaccination on pertussis immunity in Thailand. Using a series of competing transmission models, we demonstrate that declines in pertussis incidence coinciding with increases in vaccine uptake between 1984 and 1989 arose following reduction in pertussis circulation. Indeed, the maximum-likelihood estimate associated with each model points to a small or negligible transmission contribution of repeat infections, with vaccination effectively generating herd immunity.

To verify our conclusions, we use several empirical metrics to demonstrate that there is a true increase in herd immunity. We document dramatic changes in patterns of pertussis epidemiology, and quantify shifts in population measures of herd immunity. We report that over the time span of this study, there was a drastic decline in reported pertussis cases from Thailand, an effect that is especially pronounced among infants. Coincident with reduced incidence, we also found a rise in the critical community size. Overall, these observations are consistent with reduced pertussis circulation in Thailand.

Our findings shed light on key hotly debated aspects of pertussis epidemiology. First, these results indicate that current pediatric immunization programs in Thailand have successfully reduced pertussis transmission. Second, there is no empirical evidence for a resurgence in Thailand, with circulation of Bordetella pertussis effectively controlled by current vaccines. Finally, repeat infections appear to play an insignificant role in pertussis epidemiology in Thailand.

third vE�,I�� pZcentrations peaked to very high levels, to slightly decline at the end of the survey. This indicates an outbreak of B. pertussis, whereas in the other villages a pertussis endemic profile could be observed.

 

CONCLUSIONS:

Pertussis is endemic in Northern Senegal despite the introduction of vaccination. The circulation of the bacteria seems to differ between geographic locations and over time. A more complete understanding of the epidemiology of pertussis and its environmental determinants could provide information to adapt vaccination programs.

 

• The number of deaths among infants under one year of age in England with pertussis 

Eurosurveillance, Volume 18, Issue 9, 28 February 2013

The number of deaths among infants under one year of age in England with pertussis: results of a capture/recapture analysis for the period 2001 to 2011

full text, http://www.eurosurveillance.org/viewarticle.aspx?articleid=20414 

 

A J van Hoek ()¹, H Campbell¹, G Amirthalingam¹, N Andrews², E Miller¹

1. Immunisation, Hepatitis and Blood Safety Department, Health Protection Agency, London, United Kingdom
2. Statistics Unit, Health Protection Services, Health Protection Agency, London, United Kingdom

Citation style for this article: van Hoek AJ, Campbell H, Amirthalingam G, Andrews N, Miller E. The number of deaths among infants under one year of age in England with pertussis: results of a capture/recapture analysis for the period 2001 to 2011. Euro Surveill. 2013;18(9):pii=20414. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20414 
Date of submission: 14 September 2012

Pertussis activity in England in 2012 was at its highest level for more than 12 years, leading to an increased number of deaths, especially among infants who were too young to be vaccinated. To support decision making on the introduction of maternal immunisation as an outbreak response measure to prevent these early deaths, we analysed reported deaths amongst infants of less than one year of age during the period from 2001 to 2011 with a capture/recapture analysis. We used log linear regression to allow for interactions. Reported deaths were obtained from the Hospital Episode Statistics for England, death registered by the Office of National Statistics and the enhanced surveillance of laboratory-confirmed pertussis conducted by the Health Protection Agency. There were a total of 48 deaths recorded; of these 41 had a disease onset before being fully protected by vaccination. Around half of these deaths (23) were recorded in all three datasets and 10 in only one. Due to the high coverage of the datasets the estimated number of deaths missed was small with 1.6 (95% confidence interval (CI): 0.5–4.5) deaths. The total average incidence was 0.721 (95% CI: 0.705–0.763) per 100,000 maternities. We concluded that under ascertainment of deaths from diagnosed pertussis cases is small.

 

• PERTUSSIS EPIDEMIC--WASHINGTON, 2012

 

MMWR Morb Mortal Wkly Rep. 2012 Jul 20;61(28):517-22.

Centers for Disease Control and Prevention (CDC).

Abstract below; full text is at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6128a1.htm

Since mid-2011, a substantial rise in pertussis cases has been reported in the state of Washington. In response to this increase, the Washington State Secretary of Health declared a pertussis epidemic on April 3, 2012. By June 16, the reported number of cases in Washington in 2012 had reached 2,520 (37.5 cases per 100,000 residents), a 1,300% increase compared with the same period in 2011 and the highest number of cases reported in any year since 1942. To assess clinical, epidemiologic, and laboratory factors associated with this increase, all pertussis cases reported during January 1-June 16, 2012, were reviewed. Consistent with national trends, high rates of pertussis were observed among infants aged <1 year and children aged 10 years. However, the incidence in adolescents aged 13-14 years also was increased, despite high rates of vaccination with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine, suggesting early waning of immunity. The focus of prevention and control efforts is the protection of infants and others at greatest risk for severe disease and improving vaccination coverage in adolescents and adults, especially those who are pregnant. Pertussis vaccination remains the single most effective strategy for prevention of infection.

 

• PERTUSSIS TRENDS IN THE UNITED STATES

Excrept from the CDC Pinkbook chapter on pertussis, http://www.cdc.gov/vaccines/pubs/pinkbook/pert.html

Following introduction of whole-cell pertussis vaccine in the 1940s, pertussis incidence gradually declined, reaching 15,000 reported cases in 1960 (approximately 8 per 100,000 population). By 1970, annual incidence was fewer than 5,000 cases per year, and during 1980–1990, an average of 2,900 cases per year were reported (approximately 1 per 100,000 population).

Pertussis incidence has been gradually increasing since the early 1980s. A total of 25,827 cases was reported in 2004, the largest number since 1959. The reasons for the increase are not clear. A total of 27,550 pertussis cases and 27 pertussis-related deaths were reported in 2010.

During 2001–2003, the highest average annual pertussis incidence was among infants younger than 1 year of age (55.2 cases per 100,000 population), and particularly among children younger than 6 months of age (98.2 per 100,000 population). In 2002, 24% of all reported cases were in this age group. However, in recent years, adolescents (11–18 years of age) and adults (19 years and older) have accounted for an increasing proportion of cases. During 2001–2003, the annual incidence of pertussis among persons aged 10–19 years increased from 5.5 per 100,000 in 2001, to 6.7 in 2002, and 10.9 in 2003. In 2004 and 2005, approximately 60% of reported cases were among persons 11 years of age and older. Increased recognition and diagnosis of pertussis in older age groups probably contributed to this increase of reported cases among adolescents and adults.

 

• IMPACT OF ACELLULAR VERSUS WHOLE-CELL PERTUSSIS VACCINE ON HEALTH SERVICES UTILIZATION 

Am J Epidemiol. 2012 Dec 1;176(11):1035-42. doi: 10.1093/aje/kws167. Epub 2012 Nov 1.

Underestimating the safety benefits of a new vaccine: the impact of acellular pertussis vaccine versus whole-cell pertussis vaccine on health services utilization.

Hawken S, Manuel DG, Deeks SL, Kwong JC, Crowcroft NS, Wilson K.

Source

ICES@uOttawa, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.

Abstract below; full text available to journal subscribers

The population-level safety benefits of the acellular pertussis vaccine may have been underestimated because only specific adverse events were considered, not overall impact on health services utilization. Using the Vaccine and Immunization Surveillance in Ontario (VISION) system, the authors analyzed data on 567,378 children born between April 1994 and March 1996 (before introduction of acellular pertussis vaccine) and between April 1998 and March 2000 (after introduction of acellular pertussis vaccine) in Ontario, Canada. Using the self-controlled case series study design, they examined emergency room visits and hospital admissions occurring after routine pediatric vaccinations. The authors determined the relative incidence of events taking place before introduction of the acellular vaccine versus after introduction by calculating relative incidence ratios (RIRs). The observed RIRs demonstrated a highly statistically significant reduction in relative incidence after introduction of the acellular vaccine. RIRs for vaccine administered at ages 2, 4, 6, and 18 months were 1.82 (95% confidence interval (CI): 1.64, 2.01), 1.91 (95% CI: 1.71, 2.13), 1.54 (95% CI: 1.38, 1.72), and 1.51 (95% CI: 1.�
16�� pZctively, comparing event rates before the introduction of acellular vaccine with those after introduction. The authors estimated that approximately 90 emergency room visits and 9 admissions per month were avoided by switching to the acellular vaccine, which is a 38-fold higher impact than when they considered only admissions for febrile and afebrile convulsions. Future analyses comparing vaccines for safety should examine specific endpoints and general health services utilization.

• TWO ON COCOON IMMUNIZATION

 

• THE NUMBER NEEDED TO VACCINATE TO PREVENT INFANT PERTUSSIS HOSPITALIZATION AND DEATH THROUGH PARENT COCOON IMMUNIZATION

 

Clin Infect Dis. 2012 Feb 1;54(3):318-27. doi: 10.1093/cid/cir836. Epub 2011 Dec 8.

Skowronski DM, Janjua NZ, Tsafack EP, Ouakki M, Hoang L, De Serres G.

Source

Communicable Disease Prevention and Control Services, British Columbia Centre for Disease Control (BCCDC), Vancouver; Canada. danuta.skowronski@bccdc.ca

Abstract below; full text is at http://cid.oxfordjournals.org/content/54/3/318.long

BACKGROUND:

Parental immunization has been recommended as a "cocoon" strategy to prevent serious pertussis outcomes in early infancy. We illustrate the high number needed to vaccinate (NNV) for this program based on recent epidemiologic data from the provinces of Québec and British Columbia (BC), Canada.

METHODS:

Surveillance trends were summarized for the period 1990-2010. Hospitalization, intensive care unit (ICU) admission, and mortality data were compiled from 2000 to 2009. The proportion of infant pertussis attributed to a parent was estimated at 35%, explored up to 55%. Adult vaccine efficacy (VE) was estimated at 85%. The NNV was calculated as [2 parents/(parent-attributable infant risk × parent VE)]. To capture at least 1 recent cyclical peak, NNV was derived for the period 2005-2009 and explored for peak/trough years.

RESULTS:

Substantial decline has occurred in pertussis incidence across all age groups including infants, reaching a 20-year nadir in 2010 in both provinces. For the period 2005-2009, the risk of infant hospitalization and ICU admission was 57 and 7, respectively, per 100 000 in Québec and 33 and 7, respectively, per 100 000 in BC. In both provinces the risk of infant pertussis-related death over that period was <0.5 per 100 000. The NNV for parental immunization was at least 1 million to prevent 1 infant death, approximately 100 000 for ICU admission, and >10 000 for hospitalization.

CONCLUSIONS:

In the context of low pertussis incidence, the parental cocoon program is inefficient and resource intensive for the prevention of serious outcomes in early infancy. Regions contemplating the cocoon program should consider the NNV based on local epidemiology.

Comment in

Infant pertussis: what to do next? [Clin Infect Dis. 2012]

Infant pertussis: what to do next?Healy CM, Baker CJ. Clin Infect Dis. 2012 Feb 1; 54(3):328-30. Epub 2011 Dec 8.

• PARENT "COCOON" IMMUNIZATION TO PREVENT PERTUSSIS-RELATED HOSPITALIZATION IN INFANTS: THE CASE OF PIEMONTE IN ITALY.

 

Vaccine. 2013 Feb 6;31(8):1135-7. doi: 10.1016/j.vaccine.2012.12.061. Epub 2013 Jan 7.

Meregaglia M, Ferrara L, Melegaro A, Demicheli V.

Source

ASL-AL Regional Epidemiology Unit for Infectious Diseases, Alessandria, Italy.

Abstract below; full text available to journal subscribers

Pertussis incidence in Piemonte (Italy) is now at the lowest level ever reached (0.85 per 100,000 in 2010) but the disease is still endemic in infants (54 per 100,000 in 2005-2010). Parental "cocoon" immunization has been proposed in some countries (i.e. United States, France) as a measure to protect newborns from serious pertussis outcomes. We assessed the number needed to vaccinate (NNV) to prevent hospital admissions in infants (<12 months) and the potential cost-effectiveness of this strategy in Piemonte. The NNV for parental immunization was at least 5000 to prevent one infant hospitalization in the latest epidemic cycle (2005-2010) at the cost of >€100,000. The "cocoon" programme leads to net costs from a National Health Service (NHS) perspective (ROI<1). In contexts of low incidence and without reliable data on a high parent-attributable infant risk, the parental "cocoon" programme is poorly efficient and very resource intensive in preventing pertussis in infants.

Copyright © 2012 Elsevier Ltd. All rights reserved.