Sexually transmitted infections (STIs) cause significant morbidity and mortality in the United States and impose a substantial economic burden on individuals and society. Quantifying the direct medical cost of STIs in the United States can help to assess the economic impact of STIs on the population and on those who pay for their medical care.1,2 To date, there have been 3 major studies of the overall burden of STIs in the United States.2 When updated for inflation to 2010 US dollars, the estimated annual burden of STIs across all age groups were $23.0 billion (Siegel, 19973), $13.9 billion (American Social Health Association, 19984) and $16.9 billion (Chesson et al., 20041).2
Estimates of the direct medical costs of STIs are a product of 2 main inputs: the number of incident cases and the lifetime costs per case, for each of the STIs.2,5 The incidence and spread of STIs are inherently dynamic and can change over time. For instance, in the past few years, the reported annual incidence of chlamydia, syphilis, and genital warts has increased,6 although the annual incidence of gonorrhea and HIV infection has been relatively stable.6,7 In addition, given the rapid changes in health care technology and service delivery, the lifetime cost per case of STIs can change, as well. Because the published studies of the burden of STIs in the United States are 8 to 15 years old and the incidence and cost per case of STIs has changed, updated estimates are needed.2
In this study, we present the updated estimates of the lifetime direct medical cost per case of 8 major STIs in the United States. We also combine these updated costs per case estimates with updated estimates of the incidence of STIs to calculate the annual economic burden of STIs in the United States.
METHODS AND RESULTS
Following previous studies,1,2 we focused on 8 major STIs—chlamydia, gonorrhea, hepatitis B virus (HBV), human immunodeficiency virus (HIV), human papillomavirus (HPV), genital herpes simplex virus type 2 (HSV-2), trichomoniasis, and syphilis. We used similar methods for estimating the lifetime cost for each STI, as was described in the original study.1 More details on the methods are provided in the Appendix (Supplemental Digital Content 1, https://links.lww.com/OLQ/A60).
Following the previous study,1 we estimated the incidence cost of STIs in 2008 (i.e., the expected lifetime cost of new or newly diagnosed STI cases in 2008), as opposed to the prevalence cost of STIs in 2008 (i.e., the cost of treatment incurred in 2008 for prevalent STIs and STI-related sequelae regardless of when the STI was acquired1,2). To account for uncertainty, we included ranges for each cost estimate. For HPV, HIV, and HPV, the ranges were based on the lowest and highest available source estimates, as described in more detail later and in the Appendix, https://links.lww.com/OLQ/A60. For the other STIs, we assumed a cost range of ±50%, which is generally consistent with the average range of estimates for HPV, HIV, and HPV. The total direct cost for each STI (except HPV, as described later) was computed as the product of the estimated number of new or newly diagnosed cases in 20088 and the lifetime cost per case. Where applicable, future costs were discounted by 3% annually. All costs were adjusted to 2010 US dollars using the Medical Care component of the Consumer Price Index for All Urban Consumers.9
Costs were assessed for diagnosis and treatment of symptomatic cases and for treatment of asymptomatic cases. Screening costs for asymptomatic persons were not included; in our previous estimate, these costs were included as part of the overall burden of chlamydia for persons infected with chlamydia.1 We used previously published estimates of diagnosis and treatment costs for patients diagnosed in private physician/health maintenance organization (HMO) health care settings (34%)10 and other settings including STI, family planning, and other health department clinics and hospitals (66%).11 The proportion of cases diagnosed in each setting was drawn from the national STI surveillance data for 2008.
Costs of sequelae, principally pelvic inflammatory disease (PID; $3202) and epididymitis in men ($313), were included using previously published estimates.12,13 We assumed that 20% of chlamydial infections in both men and women would be symptomatic and that 89% of these cases would be treated.8,14 Of asymptomatic cases, we assumed that 40% (women 15–24 years), 15% (women 25–39 years), 9% (men 15–24 years), and 5% (men 25–39 years) were treated; these differences reflect different likelihoods of screening in each subgroup.8 Pelvic inflammatory disease was assumed to develop in 15% of untreated cases and 7.5% of treated asymptomatic cases in women, with no PID assumed to develop in treated women with symptomatic chlamydia.15 We assumed epididymitis developed in 1.5% of untreated men.16 On the basis of these assumptions and costs, we estimated that the lifetime costs per case of chlamydial infection were $30 (range, $15–$45) for men and $364 (range, $182–$546) for women in 2010 US dollars.
Gonorrhea costs were calculated in a manner similar to costs for chlamydia. Costs were assessed for diagnosis and treatment of symptomatic cases and for treatment of asymptomatic cases. Screening costs for asymptomatic persons were not included. Previously published estimates of diagnosis and treatment costs for patients diagnosed in private physician/HMO health care settings (27%)17 and other settings including STI, family planning, and other health department clinics and hospitals (73%)11 were used. The proportion of cases diagnosed in each setting was drawn from the national surveillance data for 2008.
We assumed that 50% of infections in men and 25% of infections in women would be symptomatic and that 89% of symptomatic cases would be treated.8,14,18 We assumed that 40% of asymptomatic cases in women would be treated and that 9% of asymptomatic cases in men would be treated.8 We used the same sequelae rates and costs as we used for chlamydia because of the lack of reliable literature estimates for PID and epididymitis in gonorrhea. On the basis of these assumptions and costs, we estimated that the lifetime costs per case of gonorrhea infection were $79 (range, $40–$119) for men and $354 (range, $177–$531) for women in 2010 US dollars.
Hepatitis B Virus
The lifetime cost per case of hepatitis B ($2667 [range, $2172–$2924] in 2010 US dollars) was determined by averaging the cost per case implied by 3 studies on the cost-effectiveness of HBV vaccination among adults.19–21 This cost per case estimate is notably higher than our previous estimate ($1160 in 2010 US dollars1) primarily because of updates for inflation and the inclusion of comprehensive, updated estimates of the potential costs of chronic liver disease as a result of HBV infection. For example, the potential costs of liver transplantation were included in the 3 source studies cited earlier, whereas liver transplantation costs were not reflected in our original estimate.1,22
We reviewed 2 recent studies that estimated the direct lifetime cost of HIV infection in the United States (Schackman et al.23 and Hutchinson et al.24). Schackman et al.23 used a previously published state-transition model of HIV disease and assumed a hypothetical cohort with characteristics similar to the patients who entered care at HIV Research Networks adult sites in 2002. Their primary objective was to estimate “the cost of providing the best care currently available”23 to HIV-infected patients. Schackman et al. estimated that the discounted total lifetime cost for adults entering into HIV care and initiating antiretroviral therapy was $303,100 (379,700 in 2010 US dollars). However, this estimate is applicable when considering the best-case scenario of HIV care in the United States, implying that applying their estimate could overestimate the total direct cost of HIV, because not all patients with HIV receive care and not all those who receive care get the best care available.25,26
Hutchinson et al.24 used data from the HIV Cost and Services Utilization Study and accounted for the “proportion of persons who had ever used antiretroviral therapy (ART), reported by race/ethnicity (white, 78%; black, 59%; Hispanic, 73%; and other, 77%).”24 On the basis of their assumptions and data, they estimated that the discounted lifetime cost per case was $168,600 ($229,300 in 2010 US dollars). However, Hutchinson et al.24 concluded that their estimate was likely conservative because they did not include long-term care and hospice care.
Consequently, we used the midpoint of the 2 estimates as our base value and the two estimates as the lower and upper limits for the range (i.e., $304,500 [range, $229,300–$379,700]). This midpoint estimate is close to the midpoint estimate used in the previous study ($297,600 in 2010 US dollars1), which was obtained from the classic Holtgrave and Pinkerton27 cost of HIV-related illness study in which they accounted for the possibility that some individuals will initiate treatment early, some late, and some not at all.
Unlike the other STIs, in which we assessed the total cost as the product of the cost per case and the number of cases, we estimated the burden of HPV by summing the direct medical costs of various HPV-associated health outcomes. The cost per case of HPV was calculated by dividing the incidence costs of HPV by the estimated number of cases of HPV per year. To estimate the incidence costs of HPV (i.e., the lifetime costs of HPV infections acquired in a given year), we used estimates of the incidence costs of HPV-associated health outcomes and discounted these costs for each outcome to account for the average time from HPV infection to the given outcome. This simplified approach assumes that the incidence costs of HPV-associated diseases are reasonably constant over time.
The HPV-associated health outcomes we included were as follows: cervical intraepithelial neoplasia (CIN), cervical cancer, other anogenital cancers (i.e., vulvar, vaginal, penile, and anal), oropharyngeal cancer, juvenile-onset and adult-onset recurrent respiratory papillomatosis (RRP), and genital warts. We obtained estimates of the incidence costs of each of these diseases from a recent study of the burden of HPV-associated health outcomes.28
To account for the average time between HPV acquisition and adverse health outcomes, the incidence costs of health outcomes were discounted as follows: 0 years for genital warts; 3 years for CIN; 3 years for adult-onset RRP, given that the peak ages for adult-onset RRP are similar to the peak ages of CIN; 5 years for juvenile-onset RRP28,29; and 23 years for HPV-associated cancer. Under these assumptions, the overall incidence cost of HPV in a given year was $1.7 billion: $747 million for CIN, $485 million for HPV-associated cancers, $288 million for genital warts, and $150 million for RRP.
These incidence costs ($1.35 billion in women and $0.32 billion in men), along with estimates of the annual number of cases of HPV (7,080,000 in men and 7,060,000 in women), suggest an average lifetime cost per case of HPV of approximately $45 (range, $23–$78) in men and $191 (range, $96–$329) in women. The ranges for the cost per case of HPV reflect the same relative range for the overall incidence cost of HPV-associated diseases.28 The estimated cost per case in women is notably lower than our previous estimate for 2 main reasons. First, unlike our previous estimate, our current estimate does not include the costs associated with routine cervical cancer screening. Second, estimates of the incidence of HPV are higher than in our previous study, and the estimated incidence of HPV is in the denominator of our cost per case estimate.
Herpes Simplex Virus Type 2
Owing to a lack of new cost information for HSV-2, we did not calculate new estimates of the cost per case of HSV-2 infection. Estimates of the lifetime direct medical cost per case of genital herpes (men, $761 [range, $381–$1,142]; women, $621 [range, $311–$932] in 2010 US dollars) were obtained from our previous assessment of the burden of STIs, updated for inflation.1 These previously published estimates were generated from a published model of the incidence and cost of HSV-2 in the United States30 and accounted for asymptomatic cases, which incur no costs, a general decline in the rate of relapse over time for those who are symptomatic, and the possibility of uptake of suppressive therapy.30
To estimate the lifetime cost of syphilis, we searched the literature for the most recent estimates of the cost of syphilis infection. We found one study by Owusu-Edusei et al31 that estimated the cost of primary and secondary (P&S) syphilis from the US private sector perspective ($215 in 2010 US dollars31). Using the proportion of cases reported by private physicians/HMOs in the national surveillance data as a guide, we assumed that 33% of the P&S cases were treated in the private sector and the remaining were treated in the public sector.
Finally, we used the same method and probabilities of progression into advanced syphilis infection stages adopted in the previous study1: public sector treatment of P&S syphilis (probability, 0.41; cost, $791 in 2010 US dollars); private sector treatment of P&S syphilis (probability, 0.20; cost, $21531); late-latent-stage syphilis with no lumbar puncture (probability, 0.199; treatment cost, $696); late-latent-stage syphilis, including a lumbar puncture (probability, 0.041; treatment cost, $1005); inadvertent treatment (probability, 0.134; treatment cost, $0); late benign syphilis (probability, 0.007; treatment cost, $1629); cardiovascular syphilis, including the need for cardiac surgery in some cases (probability, 0.005; treatment cost, $20,749); and neurosyphilis, including the need for long-term nursing home care (probability, 0.004; treatment cost, $84,607).1
On the basis of these assumptions and costs, we estimated that the lifetime cost per case of syphilis was $709 ([range, $355–$1064] in 2010 US dollars), which was slightly higher than the estimate in the previous study ($661, in 2010 US dollars) primarily because of the inclusion of private sector treatment costs associated with P&S syphilis.
Our search of the literature for the most recent estimates of the direct cost of trichomoniasis yielded one study that estimated the average direct cost of trichomoniasis from private insurance claims data at $121 (in 2010 US dollars).32 To be consistent with results from the incidence study,8 we assumed that 30% of trichomoniasis infections were symptomatic. We assumed that 85% of the symptomatic cases would be treated and 34% (similar to chlamydia in the national surveillance data) of the treated cases will be in private physician/HMO settings at a cost of $121, and the remaining will be treated in other settings at a cost of $69 (in 2010 US dollars).1
Owing to the lack of information on sequelae associated with trichomoniasis, we assumed that no costs will be incurred for untreated cases. On the basis of these assumptions, we estimated that the lifetime cost per case of trichomoniasis was $22 (range, $11–$33), which was slightly lower than the estimate in the previous study ($27,1 in 2010 US dollars). This difference was primarily caused by the lower proportion of cases that were assumed to be symptomatic (30% vs. 40%1) as well as our assumption that 15% of symptomatic cases will not be treated and thus incurred no costs.
Total Economic Burden
On the basis of our methods and assumptions as well as the 19.7 million incident cases, the total direct cost of the eight STIs that occurred in 2008 was $15.6 (range, $11.0–$20.6) billion in 2010 US dollars (see Table 1). Consistent with the previous study, the viral STIs (i.e., HIV, HPV, HSV-2, and HBV) make up the bulk of the cost of STIs in the United States (95%). HIV infection ($12.6 billion) alone accounted for more than 80% of the total cost of the eight STIs examined in this study. Among the nonviral STIs (i.e., chlamydia, gonorrhea, syphilis, and trichomoniasis), chlamydia ($516.7 million) was the most costly followed by gonorrhea ($162.1 million).
We estimated that for all ages for which data were available, the total direct cost of STIs was $15.6 billion (2010 US dollars) in the United States. This is slightly lower than the previous estimate of $16.9 billion, but within the reported range of $13 to $23 billion.2 The main reason for the lower estimate was the exclusion of the annual cost of routine cervical cancer screening. Had we included the annual cost of cervical cancer screening, our estimated total direct cost of STIs would have increased by approximately 37% to $21.4 billion.
Our estimate is based on estimates from other studies that have limitations. Thus, all the limitations associated with the estimates from those previously published studies are applicable. For instance, the incidence estimates that were used to compute the overall cost were based on different methods and assumptions (see the companion study by Satterwhite et al.8 for more details). Second, the lifetime cost estimates we used were based on assumptions about treatment rates, treatment efficacy, and natural history, to name a few. Third, our cost estimates for HPV assumed that the burden of HPV-associated health outcomes was constant over time, and the actual incidence cost of HPV could be notably lower or higher than we estimated.
We did not include the direct medical cost of adverse pregnancy outcomes (such as miscarriage, stillbirth, neonatal death, congenital syphilis and neonatal chlamydial conjunctivitis or pneumonia, or HSV) that are attributable to STIs. Consequently, our estimate of the cost of STIs for women was underestimated for most of the STIs examined. We focused on 8 selected STIs and did not include costs for other STIs such as HSV-1, mycoplasma genitalium infection, bacterial vaginosis, and human cytomegalovirus.1 Also, the $15.6 billion cost burden does not include the costs of sexually transmitted disease prevention, such as the cost of screening for chlamydial and HIV infections, and the cost of HPV and HBV vaccination.
Finally, our estimate does not include indirect (i.e., productivity loss) and intangible (such as pain and suffering) costs. Previous estimates of the productivity losses of STIs indicate that they are quite high and, in some cases, considerably higher than the direct medical costs.24 Thus, including indirect costs would result in a substantially higher estimated economic burden. In conclusion, our estimate is conservative, yet still indicates that STIs impose substantial health care costs in the United States.
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