Herpes simplex virus type 2 (HSV-2) is the most frequent causative organism of genital herpes (GH) in the United States, while HSV type 1 is felt responsible for this recurrent infection in only 20 to 30 percent of cases [1]. GH is contagious both in the symptomatic and in the asymptomatic phase of the disease and causes painful genital ulcers. The management of the patient involves consultations, laboratory exams and drug treatment for the disease and its complications.

GH is one of the three most widespread sexually transmitted diseases in the USA [2]. Published data show that 45 million persons aged 12 years or older have HSV-2 antibodies [3], that up to 70% of patients attending sexual transmitted disease clinics have HSV-2 infection [4] and that the majority of patients with initially symptomatic GH will develop recurrent disease [5].

Cost of illness studies represent one of the applications of economic science to medicine. The aim of these studies is to assess the economic burden of a disease and to help decision-makers in targeting preventive efforts and allocating resources [6,7]. Despite its widespread and increasing transmission, there is still poor understanding of the economic impact of GH in the USA, which makes it difficult to evaluate societal costs and the cost-effectiveness of preventive efforts [8]. Therefore, the objective of the present study was to estimate the economic burden of GH in the USA, using two different costing approaches.

We conducted a population-based study on the costs of GH. In order to give a better estimate of the disease burden, we retrieved economic information using two different approaches: In the first instance, direct interviews were conducted with a random sample of office-based physicians using a structured, comprehensive questionnaire. Secondly, information was retrieved from a large, longitudinal administrative database. For this purpose, data from Diversified Pharmaceutical Services (DPS), which is a pharmaceutical benefit management firm, were used. For both approaches, the time span was one year (1996). Costs were referred to on a yearly basis and computed in 1996 US dollars. Data were collected and analyzed separately.

This report presents crude estimates rather than precise measures of the economic costs of GH in the USA. Using two different approaches, we estimated the total direct medical costs of GH to range from a minimum of $283 million to a maximum of $984 million in 1996. Indirect costs to society amounted to $214 million due to production losses. Office-based medical care and drug treatment were the major sources of direct costs. Moreover, this study showed that the average GH patient seeking treatment is likely to be younger than 40, to develop about 2 recurrent episodes, to undergo several laboratory exams, and to be treated with antiviral drugs. Relapses tended to be shorter than first episodes though having a higher cost per episode.

Our results are likely to be conservative estimates due to the great number of asymptomatic and shedding patients not seeking medical care and transmitting the disease to other individuals. As recently shown, the great majority of people with serologic evidence of HSV-2 infection have no history of recognized GH [3]. However, many seropositive persons shed HSV-2 that is detectable by culture from the genital tract, and many have symptoms that are directly referable to HSV-2 detectable by culture [17].

From an economic point of view, it must be borne in mind that GH and other sexually transmitted infectious diseases have negative externalities in the sense that consequences of the disease are not only limited to people who have the disease but also to other people that can be potentially infected. This stems from the fact that consequences of risky sexual behavior are borne by the subject itself and by others via the transmission of the disease. In addition, it must be underlined that GH constitutes a risk factor for the spread of other sexually transmitted diseases (e.g. human immunodeficency virus), which can be interpreted as a negative consequence of GH.

The estimates of the total direct medical costs obtained with the two different approaches are discrepant and can be explained, at least in part, with the influence of compliance to treatment. It must be noted that the higher figure is obtained with data collected via questionnaire and is likely to represent the monetary value of the amount of treatment prescribed by physicians. Moreover, the reported duration of primary and recurrent GH episodes in this analysis was longer than that commonly cited in the literature [5, 8, 17], which may have artificially increased the cost estimates. The lower figure, on the other hand, is an estimate based on claims and represents the minimum amount of medical care and treatment actually consumed by patients. This difference can be expressed as the difference from what is prescribed and what is actually consumed, i.e. compliance. Thus, the difference between the two global figures may be attributable to different utilization rates or different levels of compliance. A lower level of compliance means probably lower short-term direct costs, but probably higher indirect and long-term medical costs. The hypothesis of different utilization rates is also consistent with the psychological aspects of GH, which is perceived as a potential source of shame on patients [18] and is a plausible reason for lower levels of compliance to treatment.

In a recently published article by Tao et al [16], the national direct medical costs of GH were estimated at $166 million annually for 1992-1994 ($207 million in 1999 dollars), based on claims data from several sources. These numbers may be underestimates. Tao and colleagues [16] estimated that less than 30% of acyclovir claims not associated with a specific diagnostic code were provided for the treatment of GH. As drugs account for over half of the costs attributed to GH, underestimation of drug costs substantially decreases the estimated annual costs of GH.

Based on our estimates using the DPS claims database, GH seems to be a public health problem of important economic relevance. At least $283 million can be estimated the direct health care costs attributable to GH, corresponding to 0.1% of the US health care expenditure ($1,007,300 million). However, when computing for indirect costs and long-term complications (e.g. neonatal herpes, enhanced HIV transmission), the true costs may be greater than $1.0 billion. In addition, this study has not been designed to give a monetary estimate of intangible costs of the disease. Psychological stress related to GH is well documented in the literature [18,19,20], and should be considered as a relevant factor of the total burden of illness, though not easily quantifiable.

As with any research study, limitations must he placed on the ability to generalize the results beyond the sample and setting employed. First, treatment for GH in the USA can be met at neighborhood health clinics, which offer confidential, low-cost treatment. Since a stigma is attached to the diagnosis of GH, patients may choose treatment at these clinics. The database had no information on these visits, since no claims were generated. Second, claims databases are collected for the purpose of payment to providers for the medical services rendered on behalf of enrolled members and rely on the coding of numerous medical events. Because of variations and incompleteness of coding, errors in identification and classification may occur. Coding is dependent on the diagnostic process, which is related to a clinician's training. Thus, the decision to diagnose GH by individual clinicians with different levels of expertise cannot be controlled within the boundaries of claims data. Third, the health plans included in this study allowed for geographical representation on a large regional basis. However, undetected patient, provider and practice differences may still exist. Caution should therefore be exercised in generalizing to other regions. Finally, cases selected may not necessarily be indicative of minority, low socioeconomic status, or indigent populations, since claims data can only provide data on those individuals who access the system. Therefore, the demographics of the database, in combination with the use of neighborhood clinics for GH treatment, make our calculated GH rates and costs lower bound estimates of the true GH prevalence and associated costs in the USA.

In conclusion, GH appears to be an important public health problem in the USA from the health economic point of view. The present study demonstrates the validity of using different approaches in analyzing the economic burden of a specific disease to the health care system.