Cost-Effectiveness Study of Criteria for Screening Cerebrospinal Fluid To Determine the Need for Herpes Simplex Virus PCR Testing

Abstract

The absence of markers of inflammation in the cerebrospinal fluid (CSF) commonly predicts the absence of herpes simplex virus (HSV) central nervous system (CNS) infection. Consequently, multiple authors have proposed and validated criteria for deferring HSV PCR testing of CSF in immunocompetent hosts with normal CSF white blood cell and protein levels (Յ5 cells/mm 3 and Յ50 mg/dl, respectively). Hosts are considered immunocompetent if they are Ն2 years old and have not had HIV or an organ transplant. Adoption of the criteria may erroneously exclude HSV-infected persons from a necessary diagnostic test or, alternatively, reduce the costs associated with HSV tests with minimal to no effect on patient care. Little is known about the cost-effectiveness of this approach. A decision analysis model was developed to evaluate the adoption of criteria for screening HSV tests of CSF. Estimates of input parameter values combined available literature with a multiyear multisite review at two of the largest health care systems in the United States. Adoption of criteria to screen for HSV test need proved cost-effective when less than 1 in 200 patients deferred from testing truly had an HSV CNS infection. Similar to prior studies, none of the deferred cases had HSV encephalitis (n ϭ 3120). Adoption of these criteria in the United States would save an estimated $127 million ($95 million to $158 million [Ϯ25%]) annually. The model calculations remained robust to variation in test cost, prevalence of HSV infection, and random variation to study assumptions. The adoption of criteria to screen HSV PCR tests in CSF represents a cost-effective approach.KEYWORDS cost-effectiveness, herpes simplex virus, polymerase chain reaction M ultiple studies have identified herpes simplex virus (HSV) as the most common cause of encephalitis (1-3). Unlike treatment of other causes of viral encephalitis, treatment of herpes simplex virus with acyclovir (ACV) has the highest recommendation for treatment from the Infectious Diseases Society of America (4). The combination of relatively benign treatment and a poor prognosis without treatment justifies a laboratory workup for many more patients than have the disease. The gold standard test for herpes simplex has become nucleic acid amplification, such as HSV PCR. An alternative approach to PCR proposes to test only select patients who meet specific clinical and laboratory criteria.Over the past 15 years, evidence for excluding herpes simplex virus without HSV PCR has accumulated (5-10). The authors of these studies cited five primary factors as their motivation. First, the spectrum of disease detected by PCR has become less severe and less treatable (e.g., Mollaret's meningitis, HSV-2 meningitis) (11). Second, PCR for HSV has a very low positive rate, between 1% and 3%. Most of the positive results are not

Lumbar Puncture : Indications, Complications, Technique and CSF Analysis in Pediatric Patients

“…At times, it is essential to perform ancillary CSF microbiologic testing. Polymerase chain reaction (PCR) is preferably suited for detecting fastidious organisms that may be otherwise difficult or nearly impossible to culture (such as, enteroviruses, herpes simplex virus, Borrelia burgdorferi, Epstein-Barr virus) has been particularly useful in the diagnosis of DNA and RNA viral meningitis [25] . Numerous viruses can cause CNS disease, comprising meningoencephalitis and post-infectious encephalomyelitis; even though the CSF profile is abnormal in majority (> 90%) of cases, routine CSF studies often cause identification of a specific causative agent.…”

Missing Cases of Herpes Simplex Virus (HSV) Infection of the Central Nervous System When the Reller Criteria Are Applied for HSV PCR Testing: a Multicenter Study

“…Cost-effectiveness is a factor which determines whether given laboratory screening criteria should be routinely implemented or not. Hauser and colleagues (6) showed that application of the Reller criteria for CSF HSV PCR testing is cost-effective if fewer than 1 in 200 patients deferred from PCR in fact test positive for HSV CNS infection. Hence, in our setting, we would have met this stipulation because only 1 in 629 patients would have been otherwise misclassified.…”

“…colleagues (4) suggested that HSV PCR testing can be safely deferred in patients with normal CSF white blood cell (WBC) counts and protein levels (Ͻ5 cells/mm 3 and Յ50 mg/dl, respectively), as long as they are older than 2 years of age and are not immunocompromised, either by HIV infection or transplant-the so-called Reller criteria. This assumption was later validated by another group (5) and was shown to be a cost-effective and safe approach to HSV testing (6). However, the safety of the aforementioned criteria has recently been disputed (7) and counterarguments against it have been put forward (8).…”

Screening Cerebrospinal Fluid Prior to Herpes Simplex Virus PCR Testing Might Miss Cases of Herpes Simplex Encephalitis

“…Furthermore, CSF HSV PCR has been described to be negative early on in cases of herpes simplex encephalitis (7). A potential limitation of modeling retrospective laboratory data is that a patient with herpes simplex encephalitis but a false-negative CSF HSV PCR result might have been missed by Hauser et al in their study (1).…”

“…KEYWORDS encephalitis, herpes simplex virus H auser et al make a compelling financial argument for their cost-saving approach to cerebrospinal fluid (CSF) herpes simplex virus (HSV) PCR testing using the CSF white blood cell (WBC) count and CSF total protein as a screen for the appropriate use of PCR (1). The authors do not report any instances of HSV central nervous system (CNS) infection (defined by PCR positivity) with a normal CSF WBC count in their series from two nearby institutions; however, cases of "normocellular CSF" with normal total protein have been widely reported in the literature on herpes simplex encephalitis (2-4).…”