Public health management of invasive meningococcal disease in Baden-Wuerttemberg, Germany, 2012: adherence to guidance and estimation of resources required as determined in a survey of local health authorities

Invasive meningococcal disease (IMD), caused by Neisseria meningitidis, manifests most commonly as meningitis or sepsis [1]. The incidence in Germany decreased in recent years, from 0.95 to 0.44 IMD cases/100,000 inhabitants, and similar decreases were observed in other European countries [2]. Nonetheless, even a single case can generate substantial public concern [3] because of high case fatality, propensity to affect the young and occasional appearance in clusters [4]. Modelling studies [5,6] estimated that 3–6 quality adjusted life years could be gained per case averted. Provision of antibiotic post-exposure prophylaxis (PEP) and, in case of a vaccine-preventable strain in the index case, post-exposure vaccination of defined contacts, are evidence-based measures to reduce the risk of subsequent IMD cases [7]. Household contacts of persons with IMD have a higher risk of acquiring the disease [8,9]. This also holds for close contacts in preschool settings, albeit to a lesser extent [10]. For household settings, the European Centre for Disease Prevention and Control (ECDC) estimated the number of contacts needed to be treated (NNT) with PEP to prevent one case at 284 (95% confidence interval (CI): 156–1515) [7]. For pre-school settings, NNT was estimated at 1998 (95% CI: 1307–4259). Much larger numbers of contacts would require treatment in school and university settings to prevent one IMD case [7]. By far, PEP provided to household contacts, who face the highest risk, contributes most to the prevention of subsequent cases. According to guidance of Standing Committee on vaccination and the Robert Koch-Institute (RKI) [11,12], the following persons are defined as close contacts of an IMD index case: 1) all household members, 2) contacts in the same group of an index case in kindergarten/pre-schools with children under six years, 3) household-like contacts, such as persons living in the same dormitory or military barracks as an index case, 4) persons with contact to oropharyngeal secretions of an index case, e.g. sexual partner, close friends, school contacts seated next to an index case, 5) medical staff if exposed to oropharyngeal secretions of an index case, e.g. through mouth-to-mouth resuscitation or unprotected intubation.

In Germany, IMD is statutorily notifiable by both physicians and laboratories. Cases are notified to local public health authorities (LHA) and forwarded to the state public health authorities according to a standardized case definition [13]. Surveillance data suggest that the case fatality of IMD is 8% [14].

The German Protection Against Infection Act requires local health authorities to implement measures to prevent further transmission of infectious diseases [15]. LHAs trace and manage contacts of cases with IMD according to guidance provided by the national public health institute, the Robert Koch Institute (RKI) [12], based on STIKO recommendations [11]. STIKO recommends PEP with an antibiotic that eradicates meningococcal carriage for close contacts of an IMD index case. Recommended antibiotics for children are rifampicin (20 mg/kg/b.i.d. for 2 days except 10 mg/kg/ b.i.d. for 2 days for newborns) or intramuscular (i.m.) ceftriaxone (125 mg. for < 12 year-olds, 250 mg i.m. for ≥12 year-olds), ciprofloxacin (500 mg single dose) or rifampicin (600 mg bi.d. for 2 days) for adults and ceftriaxone (250 mg i.m.) for pregnant women [11]. Post-exposure vaccination is recommended for household (-like) contacts if the IMD index case is diagnosed with a vaccine-preventable serogroup (in 2012: A, C, W, Y). Guidance on management of invasive meningococcal disease is also made available by the National Reference Laboratory for Meningococci in Wuerzburg [16], the German Society for Paediatric Infectious Diseases [17], the Working Group Meningococci of the German Green Cross for Health [18] and in a handbook on infectious diseases by Littmann et al. [19]. In December 2013, a new vaccine licensed to protect against serogroup B meningococci was made available on the European market. RKI and STIKO planned to model the impact of implementation of this meningococcal B vaccine. However, evidence on costs of public health management of sporadic IMD in Germany or other countries was lacking at the time this study was launched. A systematic review was available on the cost of managing IMD outbreaks [20], including implementation of chemoprophylaxis and targeted vaccination. Costs ranged from $2,000-56,000 (≈€1,600-45,000) per one IMD case [20], depending on the size and location (high or low income country) of the outbreaks. We performed an audit of the implementation of national recommendations for public health management of IMD in the federal state of Baden-Wuerttemberg, Southwest Germany, with a population of 10.5 million. Our objective was to evaluate knowledge of national guidance in LHAs and to describe actual implementation of management of contacts of sporadic IMD to estimate associated costs.

Our results indicated that LHAs in Baden-Wuerttemberg were aware of the available national recommendations on public health management of IMD. Almost all used RKI/STIKO guidance documents. Antibiotics for PEP advised by LHAs were all in keeping with this guidance. However, according to the cross-sectional survey, LHAs tended to advise PEP to a wider circle of contacts than recommended in the national recommendations. The retrospective case study also suggested that a substantial number of contacts without an indication received antibiotics, as LHAs advised PEP for 34 of the 47 school contacts and for all 83 health care worker contacts. On the other hand, a few household contacts (4%) were not advised to obtain antibiotics, despite all LHAs having stated that they would, in principle, advise PEP to all of these.

Only a quarter of household contacts of an index case with a vaccine-preventable serogroup were advised to receive post-exposure vaccination. A possible explanation for this is that the serogroup may not be known at the time of notification for some cases. This delay in the availability of information would make further contact necessary to advise vaccination once serogroup information becomes available. On the other hand, post-exposure vaccination was advised to a number of household contacts even though the index case was not due to a vaccine-preventable serogroup. One such contact was of adolescent age for which meningococcal C vaccine is generally recommended. Some contacts, most notably health care workers, were advised post-exposure vaccination even though this was not recommended according to RKI/STIKO guidance. A high level of anxiety upon the occurrence of IMD cases and a desire to do everything possible to prevent further occurrence of this severe disease, as well as pressure from the contacts themselves, particularly health care workers, may explain the tendency to recommend PEP or vaccination to more contacts than necessary.

Our results indicated that management of the contacts of an IMD case engaged most members of the LHA infectious disease public health team for 1–2 days, thus putting a considerable strain on the staff and likely requiring postponement of other public health tasks.

We estimated the cost of preventing a subsequent case of IMD through public health management of a sporadic cases of IMD to be ≈ €65,000. Since ≈ 3-6 QALYs are lost through a case of IMD [5,6], this amounts to ≈ €11,000-22,000 per QALY gained, or ≈ €10,000-20,000 if PEP were recommended more judiciously. While the use of cost-effectiveness thresholds is controversial and has not been applied for medical or preventive interventions in Germany thus far, threshold values applied in various countries or by certain institutions in the past considered to be cost-effective generally ranged from $20,000 to $100,000 (≈€15,000-80,000) per QALY [26]. Thus, the seemingly high cost of preventing one IMD case of €65,000 through contact management according to our study appears justifiable - also in view of the severity, high case fatality, and the high treatment costs for acute disease, complications and sequelae in a high proportion of cases [27,28]. Furthermore, the cost per IMD case prevented could be reduced if LHAs limited their advice for PEP to contacts according to national recommendations.

Our estimate of resources required for public health management of IMD cases has several limitations. First, it was based on only 41 cases of IMD from only one federal state in Germany and these do not mirror the entire range of possible contact scenarios. For instance, none of the contacts were infants or children in kindergarten/preschool. In addition, some contact scenarios applied only to a very low number of cases. Second, we may have overestimated the cost for antibiotics, as in rare cases contacts might receive single doses directly in the emergency department rather than the smallest available blister pack. However, as we chose the lowest possible price of the smallest possible quantities, it is also possible that costs were higher for some individuals. In addition, we did not include costs for any doctors’ office visits to obtain PEP, although in some cases they may have applied. Finally, we did not include the costs of post-exposure vaccination. Overall, these limitations would have led us to under-estimate the costs for obtaining PEP. Nonetheless, our results provide insight into the magnitude of costs for public health management of sporadic IMD in Germany. Since termination of our study, a British study estimated a somewhat lower cost for the public health management of a single IMD case at £317.72 (approximately €400) [29]. However, this was based on an analysis of a single index case in a cluster of two cases in a primary school. Costs for management of the two epidemiologically linked cases were 17-fold higher than management of a primary case, in keeping with the high costs found for management of IMD clusters in [20].

The awareness of national recommendations for public health management of IMD was high in LHAs of Baden-Wuerttemberg. However, LHAs advised PEP to a wider circle of contacts than specified in the recommendations. At the same time, implementation of post-exposure vaccination among household contacts with a vaccine-preventable serogroup was markedly underused. To close this identified knowledge-practice gap, we encouraged LHAs to limit advice for PEP to contacts as defined in national recommendations and to improve implementation of post-exposure vaccination for household contacts. A better implementation of the national recommendations would optimize prevention and avoid unnecessary expenses. Finally, our results provide insight into the costs of public health management in Germany for the first time and are being used to parameterize a model to estimate the costs and benefits of meningococcal B vaccination in Germany.