How to Save Money: Congenital CMV Infection and the Economy

Abstract

Human cytomegalovirus (CMV) is the main cause of congenital virus infection in developed countries leading to psychomotor impairment, deafness and blindness. In Germany each year, estimated 6500 children are born with congenital cytomegalovirus (CMV) infection, causing estimated 40 deaths and leaving approximately 1200 children (primary infected and from seropositive women) with permanent disabilities such as hearing or vision loss or mental retardation. More children are affected by serious CMV-related disabilities than by several better-known childhood maladies, including Down syndrome [1].

Addendum

• Gabriele Halwachs-Baumann 

In January 2018 a cost-of-illness study was published by Korndewal et al. [1], calculating the costs of congenital CMV. As a result it was shown, that the average healthcare costs of children with congenital CMV in the first 6 years of life are much higher than that of children without congenital CMV (€ 6113 vs. € 3570, converted to 2018 US dollars i.e. $ 7327 vs. $ 4279). For those children with long-term impairments the healthcare costs are twice as high in children with congenital CMV (€ 17,205, i.e. $ 20,624) compared with children without congenital CMV (€8332, i.e. $ 9987). This emphasizes the evidence that congenital CMV is not only a massive health problem, but also (for those who believe in an economic view of the world) an enormous economic problem. Additionally there are several reasons to presume that the actual difference in health care costs between the congenital CMV-positive and congenital CMV-negative children is larger than found in this study, since children who died of congenital CMV within the first 5 years of life were not included, and the healthcare costs were estimated only up to 6 years of age [1]. Calculating the cost for the whole life this would multiply the direct cost for congenital CMV infection by ten, as shown in the chapter before. So reducing the number and the severity of congenital CMV infection will definitely save money. Nevertheless, the amount of reduced costs depends on the choosen defence strategy.

To fight congenital CMV infection different approaches are under discussion:

• 1. Vaccination as it is performed to eradicate congenital rubella syndrome.

• 2. Education on hygienic procedures to avoid infection during pregnancy

• 3. Screening pregnant women and prophylaxis/therapy with hyperimmune globulin in the case of primary CMV infection

• 4. Screening newborns and treatment with antivirals

Although it sounds easy, a lot of questions arise. In the case of vaccination despite the issue which vaccine should be used, it is important to decide the group of people who should be vaccinated. For rubella four different strategies are described [2]: in the United States vaccination of all children to create herd immunity and later, revaccinating all young adult women is performed. The program of the United Kingdom includes vaccination of teenage girls and sero-negative women plus contraception for three months after vaccination. The Swedish program consists of vaccination in early childhood and re-vaccination of all teenagers. In Iceland a selective vaccination involving puerperal women as well as all women of child bearing age who are willing to use contraceptives for three months is performed. For rubella it was shown that vaccination to prevent congenital rubella syndrome is more cost-beneficial than vaccination to interrupt rubella transmission [2]. Furthermore, since vaccine prices have fallen over the year, it was mentioned that blind vaccination has become more favorable compared to targeted vaccination.

For congenital CMV infection vaccinating all adolescent females prior to their first pregnancy would cost $ 32.3 million dollars less than not vaccinating. This was true under the presumption that vaccine efficacy against disease is at least 61%. When vaccine efficacy against disease was less than 61%, not vaccinating would became the preferred strategy because it was less expensive than vaccinating, without substantial changes in clinical benefits to the population [3]. In the paper from N’Diaye et al [4] also the vaccinating strategy was evaluated. They compared their current practice, which consists of hygiene counseling, with routine vaccination of all adolescent women aged 14 years old, and screening and vaccination of the seronegative women as third strategy. The results were similar to those found by Dempsey et al: Systematic vaccination of adolescent girls was found to be the most efficient strategy to prevent maternal seroconversons. As a limitation seroprevalence was mentioned. If the seroprevalence was more than 62% screening and vaccination of seronegative would become the most efficient strategy [4].

Vaccinating strategies to prevent congenital CMV infection must be viewed under the perception, that the burden of CMV transmission and disease following non-primary infection in pregnancy may be higher than previously anticipated [5]. The fact that preexisting immunity of the mother is an incomplete protective shield against transmission is known for a long time. Nevertheless, transmission rate in primary infections is said to be 30% opposed to a rate between 1 and 2% in non-primary infections [5]. So it seems to be worthwhile to evaluate vaccination strategies not only with the goal to prevent transmission in seronegative women, but also to enlarge immunological defense against CMV transmission in seropositive women. That means that trying to stimulate immune responses similar to those seen in natural infection may not suffice to protect all women against CMV transmission to their offspring [5].

One of the most economic intervention strategies to prevent infection of women is an educational approach. As it is known the shedding rate of healthy young children is much higher than that of seropositive healthy adults [6]. Thus toddlers are likely transmitters of CMV to their mothers, or other persons taking care of these children for example in a crèche or a kindergarten. Giving women instructions about protective behaviors and risky behaviors to avoid, seroconversion rate can be halved [7]. Since the percentage of people who have heard of congenital CMV is alarmingly low (7 % of men, 13 % of women), educational programs would be an effective way to reduce CMV transmission to pregnant women [8, 9, 10]. Although compared to other prevention strategies information and education is the least effective strategy, it is also the least costly [4], with no side-effects and no investments but time. So this should be the least to fight against congenital CMV infection.

As discussed in the study above prophylaxis with hyperimmuneglobulin is another option to prevent congenital CMV infection. Universal screening for primary maternal CMV infection with intention to treat with CMV i.v. immune globuline was shown to be the most cost-effective strategy compared to selective screening strategies [11, 12]. However, if immunoglobulin treatment achieves less than a 47% reduction, other strategies would be more cost-effective.

To evaluate the efficacy of CMV hyperimmunglobulin administration during pregnancy it is important to differentiate whether this intervention was to prevent transplacental transmission from mother to child, or it was given as therapeutic application to reduce symptoms in the yet infected unborn. Since it is crucial to find the point in time at which transmission has already occurred, results on the efficacy of hyperimmunglobulin administration are sometimes contradictory. We can hope that ongoing studies will elucidate these problems.

One strategy to fight the harm caused by intrauterine CMV infection which is quite well investigated is the antiviral intervention after birth. Cost effectiveness of newborn screening was evaluated under a wide range of assumptions. Most studies focused on the prevention or at least improvement of hearing loss. Since hearing loss after congenital infection is a slow progressive disease, antiviral treatment is an effective intervention. These clinical experiences are substantiated by pathophysiological investigations [13]. The estimated total lifetime costs of severe or profound hearing loss are $ 280,000 per child, plus an estimated productivity loss of $ 926,000, resulting in approximately $ 1.2 million total costs [14], which incur if nothing is done. Comparing these costs with those arising by screening and therapy programs, every economist must rise up his hand to vote for programs reducing the problems induced by congenital CMV. So compared to the above mentioned cost of ignorance, the estimated costs of identifying a case of congenital CMV-related hearing loss by targeted congenital CMV screening using salivary swabs vary between £ 9224 and £ 5413 (converted to 2018 US dollars i.e. $ 12,390 and $ 7,273). The costs of ‘protecting’ a case of congenital CMV related hearing loss by antiviral treatment vary between £ 19,601 and £ 11,502 (converted to 2018 US dollars i.e. $ 26,330 and $ 15,450). These are costs comparable to other screening and interventions programs used for the detection of phenylkentonuria or cystic fibrosis [15]. Just focused on the mitigation of hearing loss by antiviral treatment public savings will offset the public costs incurred by screening and treatment if just one infant per year benefits from this program [16]. This is accompanied by costs of $ 2000–$ 10,000 for identifying one case of congenital CMV infection among all infants born in the United States by universal screening and $ 566–$ 2832 by targeted screening. Just focused on identifying hearing loss due to congenital CMV detecting one case costs $ 27,460 by universal screening or $ 975 by targeted screening. Also in this study universal as well as targeted screening reduce total costs under most assumptions [14]. It was even shown that net savings from universal screening were greater than those from targeted screening, although screening costs are higher.

Taking together it can be said that whatever the program is you choose to reduce the number of children congenitally infected with CMV or to mitigate symptoms due to congenital CMV infection—there is a benefit not only from a medical and humanitarian point of view but also from an economical point of view. The most expensive action is to be in denial and to do nothing.

References

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