pertussis epidemics increasing

The CDC reported on the epidemiology of pertussis in the United States from 2000-2016, noting a significant increase in cases over time and suggesting that the acellular pertussis vaccine was suboptimally effective (see pertussis epidemiol 2000-16 clininfdz2018, or DOI: 10.1093/cid/ciy757 )

Details:

-- this includes cases reported through the National Notifiable Diseases Surveillance System

Results:

-- 2000-16: 339,420 pertussis cases reported

-- 88% white, 81% non-Hispanic, 10% hospitalized, 0.1% fatal

-- age breakdown:

    -- infants<1-year-old: 15.1% of cases, 75.3/100,000

    -- kids 1 to 6 years old: 16.8% cases, 13.8/100,000

    -- kids 7 to 10 years old: 15.0% of cases, 18.3/100,000

    -- 11 to 18 years old: 27.7%, 16.3/100,000

    -- 19 to 29 years old: 3.3%, 1.4/100,000

    -- 30 to 64 years old: 19.7%, 2.8/100,000

    -- >65 years old: 2.4%, 1.2/100,000

-- the proportion of cases in black and Hispanic persons was significantly higher among infants aged <1-year-old (14% and 36.4%, respectively); the proportions decreased steadily with age

-- hospitalization rates were highest among infants <1-year-old (50%) followed by adults > 65 (14%)

-- 294 deaths from pertussis: 261 (89%) in children<1-year-old, and 14 (5%) in those > 65

-- trends over time: though incidence was cyclic, ranging from a low of 2.7/100,000 in 2001 to a high of 15.4/100,000 in 2012, the increasing trend over time was statistically significant (p=0.0019)

-- geographical trends: highest in the West North Central and Mountain regions, though at various times were also high in Pacific and New England regions. Lowest rates were in the South Atlantic and East South Central regions.

-- a review of their timeline (figure 1): adding the Tdap vaccine in 2005 for adolescents (they had the second highest rate of infection by age-group) led to more than 50% decrease in pertussis cases overall. 

Commentary:

-- in the 1940s in the US the annual number of reported cases of pertussis exceeded 200,000

-- with the advent of pertussis vaccine, reported cases declined to just over 1000 by the mid-1970s (0.47/100,000 population)

-- because of safety concerns/adverse reactions, an acellular vaccine DTaP was introduced between 1992 to 1997.

-- Because of waning pertussis immunity, in 2005 a single dose of Tdap was recommended for adolescents and adults, preferably at ages 11 to 12.

    -- Adolescent immunization rates were 88%, significantly lower in adults at 27% in 2016

-- as an overview of the above trends (and lots of data points were not included: the study was littered with data):

    --overall baseline pertussis incidence has increased 2-fold when comparing the later vs earlier time-periods of the study

    --2012 had the largest number of cases since the 1950s, at 15.4/100,000, representing >48,000 reported cases

    --the  introduction of the adolescent Tdap booser in 2005 (because of the high number of cases in that age group) led to important decreases in pertussis cases

    --but in 2008, more cases emerged in those 7-10 years old, despite high prior DTaP immunization coverage, suggesting inherent limitations of this vaccine

    --subsequent increases in 13 and 14 year olds was also observed, again suggesting deficiencies of the vaccine

    ​--as they observe: "stratification of national data by single year of age illustrates the close correlation of this trend with the aging of the first acellular-primed birth cohort from 1998"​ (ie, people were aging out of protection from the vaccine)

-- one concern with pertussis overall is that neither vaccination nor prior infection confers life-long immunity (ie, booster doses of vaccine seem to be necessary no matter what)

-- since 2012, Tdap vaccine has been recommended for pregnant women during every pregnancy. This was to increase the resistance of infants <2 months old, by passive transfer of immunoglobulins from the mother and prior to the usual 2 month infant vaccination against pertussis (see blog http://gmodestmedblogs.blogspot.com/2018/10/vaccine-approved-to-age-45-tdap-best.html , which suggests that optimal passive antibody transfer to the neonate was at 30 weeks gestation)​. It is likely that improving these immunization rates in pregnant women will help decrease the high incidence rates/hospitalization rates/mortality in kids <1yo

--however, a few prior blogs do go into some detail on the marginal effectiveness of the acellular vaccine:

    -- https://blogs.bmj.com/bmjebmspotlight/2015/03/19/primary-care-corner-with-geoffrey-modest-md-pertussis-vaccine-not-quite-up-to-snuff/​ blog from 2015, which reviewed some of the data on emerging pertussis infections, adverse effects of the old DPT vaccine (eg 1 in 330 kids had fever >105 deg), and prior studies showing, for example, that kids developing pertussis were more likely to have gotten the DTaP earlier, and a baboon study showing that there was actually a much different T-cell response to acelluar pertussis vaccine vs either the old vaccine or with natural infection with pertussis

    -- https://blogs.bmj.com/bmjebmspotlight/2015/05/21/primary-care-corner-with-geoffrey-modest-md-pertussis-vaccine-in-adolescents-and-only-transient-immunity/ for another blog in 2015 showing dramatic decreases in DTaP effectiveness over time in adolescents (eg, 73% efffective if last DTaP within 12 months, decreasing to 55% if 12-23 months, then to 34% if 24-47 months).

--of course, as well as waning immunity from the non-optimally effective acellular vaccine,  there are several concurrent issues which could affect the validity of the results. for example, there has likely been more awareness of pertussis over time, leading to more diagnoses; more sensitive and rapid PCR testing, some molecular changes to the bug which might help it escape vaccine coverage

--another recent study assessed data from 7 US Emerging Infections Program Network states from 2011-2015 , looking at severe pertussis infections (see pertussis severe infections inc clininfdz2018  in dropbox, or doi.org/10.1093/cid/ciy889 ), finding that:

    -- Pertussis incidence was relatively stable during 2011 and 2013-15, ranging from 8.5 to 14.8 cases per 100,000, and peaked in 2012 with an incidence of 42.0 cases per 100,000 population. The average annual incidence by state ranged from 3.5 to 33.0 cases per 100,000 population, with the 2012 peak reported in all sites. The proportion of pertussis patients who were hospitalized was lowest in 2012 at 2.3%, and was relatively stable during 2011 and 2013-2015, ranging from 3.3% to 4.6%.

    --of 15,942 pertussis cases, 515 (3.2%) were hospitalized and 107 (21.0%) of the hospitalized patients required ICU admission

    --infants <2mo old accounted for 1.6% of cases but 29.3% of hospitalizations: they had 26.2 times the risk of hospitalization and 72 times the risk of ICU admission compared to all other age groups combined

    --those <2mo old but whose mothers got the Tdap in pregnancy had a 43-66% decreased risk of hospitalization, as did kids 2 months to 11yo who were up to date on immunizations [?would there have been fewer cases if pregnant women were immunized at 30 weeks?)

    --of the 23 teens hospitalized, 10 (43.5%) had history of asthma, and in adults >=65yo, though only 41 were hospitalized, 11 had a history of COPD (26.8%)​

So, these articles suggest a few things:

--our current vaccine is woefully inadequate: we really need a new one, at least as effective as the old pertussis vaccine but safer. And one preferably with life-long immunity…

--with the current vaccine, it seems that we need lots of boosters to get effect, not just one in adults (it is telling that pregnant women are supposed to get a booster with each pregnancy)

--maybe there should be more risk stratification with the current vaccine (eg, as with pneumococcal vaccine): it appears that those with underlying lung disease seem to do worse. Should those with with asthma, copd, maybe others​ be targeted to get more frequent vaccinations? And those at the extremes of ages? eg maybe more vaccinations in specific age groups (eg more boosters after age 65??)?? Perhaps we should really make sure that pregnant women get the vaccine, preferably at 30 weeks gestation? This type of targeting by risk groups may be helpful even with our currect suboptimal vaccine...

geoff​

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