Despite a high level of vaccination coverage,1 worldwide pertussis still causes in excess of 60,000 deaths annually in children under five years of age.1 The consequences of pertussis are particularly severe in newborns and infants,1-5 and life-threating complications and death are most likely in those less than 6 months of age.1-5 Pertussis vaccination programmes generally commence with a first dose age six to eight weeks, although in some countries, vaccination may begin as late as 12 weeks of age.1, 6 Hence, in the first few weeks and months of life, many infants are unprotected or have only partial protection, as they have not completed the full course of vaccinations.1 The World Health Organization (WHO) has recently considered vaccination of newborns against pertussis, but it was considered that there are insufficient safety data to support use of currently available vaccines in this age group.1 It has also been suggested that vaccination during the early stages of life may not induce adequate protection.2 Other vaccination strategies are therefore needed to protect young infants. Two approaches, maternal immunization during pregnancy and so-called cocooning vaccination, have been considered in recent years.
Sources of Infection
The risk of contracting pertussis as a result of transmission from a close contact is higher for infants younger than six months of age than for older children or adults.6 Waning of vaccine-induced immunity in close contacts has been long been identified as a risk factor for transmission to infants,7and studies have been conducted to determine which close contacts are involved.7, 8 A review of nine studies on transmission of pertussis to infants concluded that where sources of infection were identified, most were family members or other household contacts (Figure 1).7
The objective of the cocooning strategy is to protect the infant against pertussis through vaccination of all those likely to be in close contact before it is vaccinated and who have been identified as potential sources of infection, including family members and healthcare workers.1, 6, 9
Studies on the clinical benefits of cocooning strategies have reported varying results. An Australian study during an epidemic, parental vaccination reduced risk by 51%;10 however, another Australian study found that parental postpartum vaccination within the four weeks following their child’s birth did not reduce the risk of infection.11 Further, a US retrospective analysis found that postpartum maternal immunization and cocooning strategies did not reduce illness in infants ≤6 months of age.12 Cocooning strategies have also been reported to be challenging to implement in some countries.1
Cost-effectiveness analyses of cocooning have yielded varying results. A recent Spanish study found that the benefit-to-cost ratio for cocooning was lower than that of vaccination during pregnancy.13 In addition, in a decision analysis of US data, maternal vaccination during pregnancy resulted in fewer infections and deaths at a lower cost than either postpartum maternal vaccination alone or in combination with a cocooning strategy. A study from the Netherlands, by contrast, found that cocooning was more cost-effective than maternal vaccination during or after pregnancy.14
The outcomes of computer modelling evaluations of cocooning strategies have been mixed, with a number suggesting that under conditions of low pertussis incidence the strategy would be resource intensive and not efficient in preventing infection;6 whereas another found that parental vaccination would yield some protection and be cost effective under a range of conditions.15
Maternal vaccination is most likely to have the greatest effect on transmission to newborns compared to vaccination of other close contacts,7 with vaccination during pregnancy enabling the maximal maternal response to the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine to be reached before birth.9 More important than protecting against maternal transmission, however, passive transfer of maternal antibodies takes place prior to birth following Tdap vaccination during pregnancy,6, 16-18 providing direct protection in the critical few weeks before the infant is vaccinated.16
The efficacy of maternal Tdap vaccination during the third trimester has been demonstrated in a range of studies.1, 6 A case-control study in England and Wales in 2012/13 showed an adjusted vaccine effectiveness (VE) of 93% in infants following maternal vaccination,19 whilst an observational study in England in this same time period found 90% VE in infants <2 months of age,20 and a Californian study in a similar age group found vaccination during the third trimester to be 85% more effective than post-partum vaccination.21 The safety of maternal vaccination for the infant is supported by recent UK data.22
According to the WHO, cocooning may have an impact on disease prevention in some settings if coverage is high and timely, although the benefit is likely to be less than with maternal immunization during the third trimester.1 In the United States, for example, ACIP recommend that adolescents and adults who have not previously been vaccinated with Tdap but who are likely to have close contact with newborns should receive a single dose;9 guidance from ACIP on revaccination of close contacts is awaited. A strong case has, however, been made for immunization of mothers during the third trimester of pregnancy, which is now recommended by WHO in addition to routine infant vaccination programmes when there is high or increasing infant mortality, and similarly included in many national guidelines.1, 6, 9
The Global Pertussis Initiative considers that the current evidence supports maternal Tdap immunization during pregnancy as the primary strategy for protection of newborns from pertussis (Figure 2). Should this not be possible, or if families prefer additional protection for their infant, all potential close contacts could be immunized during the pregnancy or immediately postpartum according to local guidelines. In these circumstances, high priority should be given to achievement of a complete cocoon, or if this is not possible, vaccination of both parents, or failing that, the mother only.6
In summary, cocooning strategies should be considered as an adjunct to maternal vaccination during pregnancy, which should be the highest priority for protection of newborn infants from pertussis infection.
GPI recommendations to avoid newborn and infant pertussis deaths and severe disease. Protection by cocooning depends on vaccinating all who come into contact with the infant. About 2 weeks are required for antibodies to develop in vaccinated contacts.
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