Clinical significance: Actinomyces israelii is a filamentous anaerobic gram-positive bacteria. The infection begins as an inflammatory soft tissue mass, which can enlarge into an abscess-like swelling. All species of Actinomyces are normal commensal inhabitants of the oral and buccal cavities in humans and certain other mammals. The anaerobic actinomycetes are not transmitted sexually and are not generally considered as part of the normal vaginal flora. Colonization in the female genital tract is stimulated greatly by the presence of a foreign body such as intrauterine contraceptive devices (IUCDs), hairpins, and even surgical sutures. Colonization may be asymptomatic or minimally symptomatic, presenting only as shedding of actinomycotic granules into the vaginal fluid. The clinical presentation includes foul-smelling vaginal discharge, intermittent pelvic pain, abnormal bleeding and one or more pelvic masses. In the acute phase, pelvic abscesses are often unilateral, involving a single fallopian tube and ovary. Single or multiple abscesses may form in the uterine wall, usually surrounding an embedded IUCD. The most extensive disease may present with a frozen or “woody” pelvis demonstrating extensive adhesions and scarring as part of the inflammatory response. A subset of genital actinomyces cases will present with some abnormalities of vaginal fluids on PAP smear. Anaerobic actinomycetes are successfully cultured in only about 10% of those cases investigated, which makes molecular amplification techniques an attractive option for the clinical diagnosis of vaginal actinomyces. The anaerobic actinomycetes are considered universally susceptible to penicillin, which is the drug of choice if antibiotic therapy is needed.

Clinical significance: Adenoviruses cause a number of self-limiting but often highly infectious diseases that affect multiple organs, most commonly those associated with the respiratory and genitourinary tracts. They are non-enveloped icosahedral particles that contain double-stranded DNA. Adenovirus is a relatively harmless pathogen in healthy individuals, but can cause a variety of symptoms in young children and the immunocompromised. Transmission can occur from direct person-to-person contact, or through contact with a contaminated surface or object. Adenovirus is usually asymptomatic, and may cause a variety of symptoms including respiratory problems, gastroenteritis, pink eye, pharyngoconjunctival fever, skin rashes, and genitourinary tract infections including cervicitis, urethritis and hemorrhagic cystitis. The most severe cases of adenovirus infection may result in pneumonia, croup, and bronchitis. In this assay DNA is extracted from the patient specimen and subjected to PCR amplification.

Clinical significance: Bacterial vaginosis (BV) is a polymicrobial syndrome that represents a disturbance of the vaginal ecosystem through a shift in the microflora. Several adverse medical outcomes have been associated with BV. While the cause of BV is not understood, some strong associations have been made between the syndrome and the presence of particular bacterial species, such as Gardnerella vaginalis. Atopobium vaginae, an anaerobic bacteria, has also been implicated in BV. A recent study by Bradshaw et al., (2006) stated that A. vaginae is more specific for BV and abnormal vaginal flora than G. vaginalis (n=358). In addition, G. vaginalis was common in women with normal vaginal flora (60%), whereas, A. vaginae was uncommon (12%) in the normal population (p<0.001). The population with confirmed BV had both organisms present (96%), compared to women with normal vaginal flora (10%) (p<0.001). High levels of G. vaginalis (>4x10⁵ copies/ml) and A. vaginae (>4x10⁶ copies/ml) were significantly more common in women with BV.

132 Gardnerella vaginalis by Real-Time PCR
124 Mobiluncus mulieris and M. curtisii by Real-Time PCR
125 Bacteroides fragilis by Real-Time PCR

Clinical significance: Bacterial Vaginosis (BV) is a leading cause of abnormal vaginal discharge and odor. It constitutes a massive microecologic alteration of the vaginal flora. BV is characterized by: (1) decreased or absent Lactobacillus spp., (2) a logarithmically increased concentration of Gardnerella vaginalis (>10^8 to 10^11 CFU/g) (3) logarithmically increased concentrations of a set of potentially pathogenic bacteria, including Bacteroides spp. and Mobiluncus spp., along with Ureaplasma urealyticum and Mycoplasma spp. BV is related to considerable, and possibly preventable, infectious morbidity in non-pregnant women. The sequelae of BV now includes endometritis, pelvic inflammatory disease, post-surgical abortion infections, post-hysterectomy infections, an increased risk of HIV acquisition and, possibly, cervical intraepithelial neoplasia. The diagnosis of BV is complicated by the polymicrobial nature of the condition. Fifty percent of patients diagnosed with BV show no symptoms. Furthermore, patients in the intermediate and the normal categories are generally not considered for treatment according to the Nugent criteria. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Bacteroides fragilis is an anaerobic bacteria that is commonly associated with Bacterial Vaginosis. BV is a leading cause of abnormal vaginal discharge and odor. BV constitutes a massive microecologic alteration of the vaginal flora. It is characterized by: (1) decreased or absent Lactobacillus spp. (2) a logarithmically increased concentration of Gardnerella vaginalis (> 10^8 to 10^11 CFU/g) (3) logarithmically increased concentrations of a set of potentially pathogenic bacteria, including Bacteroides spp. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Bacteroides ureolyticus is an obligate, aneareobic, gram-negative rod that was first described in clinical specimens in 1948. It is the most frequently isolated Bacteroides species, after Bacteroides fragilis. It has been isolated from mixed cultures of infections involving nearly every organ system in humans. It is associated with ulcerative lesions of both the external and internal genitalia including  the perineal area, and abscesses. It is also a pathogen of the urinary tract. It has been implicated in non-gonoccocal urethritis (NGU).  One study detected B. ureolyticus in 50% of men with NGU. It is thought to cause damage to the urethral mucosa via an endotoxin. In this assay, DNA is extracted from the patient specimen and subjected to PCR amplification.

Clinical significance: Between 85% to 90% of yeast strains isolated from the vagina belong to the species of Candida albicans. Candida albicans is one of the major causes of Candida Vaginitis (CV). CV affects most females at least once during their lives, at an estimated rate of 70% to 75%, of whom 40% to 50% will experience a recurrence. In the United States CV is currently the second most common cause of vaginal infections, with bacterial vaginosis the most common diagnostic entity. Most studies indicate that CV is a frequent diagnosis among young women, affecting as many as 15% to 30% of symptomatic women visiting a clinician. By the age of 25, half of all college women will have experienced at least one episode of CV. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Candida dubliniensis is associated with oral candidiasis and has been recovered from the vaginal tract of women. Although it is closely related to C. albicans, its differences in virluence and its ability to rapidly develop resistance to traditional anti-fungal agents makes it very clinically relevant. The use of molecular techniques, such as Real-Time PCR, enables the clinician to differentiate C. dubliniensis from other species of Candida to facilitate diagnosis and proper treatment.

Clinical significance: C. glabrata accounts for 7% of all vaginal fungal infections and about 10% of vaginal yeast isolates. It is thought that the widespread use of topical antifungals, especially in short courses, may contribute to selection for non-albicans yeasts, which are less susceptible to these agents than C. albicans. C. glabrata is associated with Candida Vaginitis (CV). CV affects most females at least once during their lives, at an estimated rate of 70% to 75%, of whom 40% to 50% will experience a recurrence. In the United States CV is currently the second most common cause of vaginal infections, with bacterial vaginosis the most common diagnostic entity. Most studies indicate that CV is a frequent diagnosis among young women, affecting as many as 15% to 30% of symptomatic women visiting a clinician. By age 25 years, half of all college women will have experienced at least one episode of CV. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Only performed after a #559 is positive.
Charges will be the total of tests #559 + #579.

Clinical significance: C. glabrata has emerged as the primary non-albicans species in Candida Vaginitis (CV), accounting for up to 20% of infections in immune-competent women. It is thought that the widespread use of topical antifungals, especially in short courses, may contribute to the selection of non-albicans yeasts, which are less susceptible to these agents. C. glabrata has also been shown to intrinsically exhibit low level resistance (MIC= 16 to 32 µg/mL) requiring increased drug regimen dosages for eradication. C. glabrata also acquires true azole-resistance, as defined by MIC levels of =64 µg/mL, resulting in failed drug treatment even at higher drug regimen. Resistance to antifungals is conferred through the over-expression of the drug efflux pump, CDR1; this dysregulated expression allows the resistant yeast to survive and proliferate. This assay is performed only after a positive result from test 559, Candida glabrata by Real-Time PCR, is obtained as a means to aid physicians in determining the proper course of treatment for their patients. This assay requires the extraction of RNA from the clinical specimen for analysis of CDR1 gene expression by quantitative reverse transcriptase PCR.

Clinical significance: Candida kefyr is one of the six strains of Candida, of approximately 154 species, that is commonly associated with infections of humans. This species, previously reported in the literature by the obsolete name of Candida pseudotropicalis, has been reported as an emerging pathogen. Candidiasis has a wide clinical spectrum, capable of affecting almost any organ or system in the body. Infections range from localized, superficial infections to dissemination in the blood stream. Considered to be a relatively rare infection, found in approximately 1% of fungal isolates, reported infections include burn wounds, blood and vaginal infections. More recently, the frequency of C. kefyr infections has increased within oncohematologic patients, particularly those with neutropenic, myeloid and lymphoblastoid leukemias.

Clinical significance: Candida krusei, which has traditionally been implicated in urinary tract infections, has recently been associated with certain instances of fungal vaginitis, particularly recurrent fungal vaginitis. The use of molecular techniques, such as Real-Time PCR, enables the clinician to differentiate C. krusei from other species of Candida to facilitate diagnosis and proper treatment.

Clinical significance: Candida lusitaniae is considered a nosocomial bloodstream pathogen that is becoming increasingly associated with Candidemia. It is also quite resistant to amphotericin B, a common antifungal treatment.

Clinical significance: C. parapsilosis accounts for 1% of vaginal yeast isolates. It is thought that the widespread use of topical antifungals, especially in short courses, may contribute to selection for non-albicans yeasts, which are less susceptible to these agents than C. albicans. C. parapsilosis is associated with Candida Vaginitis (CV). CV affects most females at least once during their lives, at an estimated rate of 70% to 75%, of whom 40% to 50% will experience a recurrence. In the United States CV is currently the second most common cause of vaginal infections, with bacterial vaginosis the most common diagnostic entity. Most studies indicate that CV is a frequent diagnosis among young women, affecting as many as 15% to 30% of symptomatic women visiting a clinician. By the age of 25, half of all college women will have experienced at least one episode of CV. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Candida tropicalis is isolated from 1% to 5% of vaginal yeast isolates and may be associated with a higher rate of recurrence after standard treatment. It is thought that the widespread use of topical antifungals, especially in short courses, may contribute to selection for non-albicans yeasts, which are less susceptible to these agents than C. albicans. C. tropicalis is associated with Candida Vaginitis (CV). CV affects most females at least once during their lives, at an estimated rate of 70% to 75%, of whom 40% to 50% will experience a recurrence. In the United States CV is currently the second most common cause of vaginal infections, with bacterial vaginosis the most common diagnostic entity. Most studies indicate that CV is a frequent diagnosis among young women, affecting as many as 15% to 30% of symptomatic women visiting a clinician. By the age of 25, half of all college women will have experienced at least one episode of CV. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Candida utilis has traditionally been described as an industrially significant yeast. However, it was recently implicated in a case of recurrent urinary tract infection and candidemia. It has also been associated with fungal keratitis. The use of molecular techniques, such as Real-Time PCR, enables the clinician to differentiate C. utilis from other species of Candida to facilitate diagnosis and proper treatment.

551 Candida albicans by Real-Time PCR
557 Candida tropicalis by Real-Time PCR
558 Candida parapsilosis by Real-Time PCR
559 Candida glabrata by Real-Time PCR

Clinical significance: The incidence of Candida Vaginitis (CV) is poorly documented, particularly since CV is not a reportable entity. Regrettably, without laboratory confirmation, CV is misdiagnosed in as much as 50% of cases. Ninety-one percent of yeast strains isolated from the vagina belong to the species of Candida albicans. Other vaginal yeast strains isolated include C. glabrata, C. parapsilosis, and C. tropicalis, accounting for the remaining CV cases in the United States. Vulvovaginal candidiasis accounts for about one-third of all the vaginitis cases seen in private practices. Patients with CV generally complain of perivaginal pruritus, often with little or no discharge. Currently, CV diagnosis is based on the addition of 10% potassium hydroxide to vaginal discharge on a slide (the “whiff” test). However, the whiff test fails to elicit a confirmatory odor in most women with CV. Direct microscopic examination of wet mount vaginal discharge fails to reveal the fungi in 30% to 50% of infected women. A commercially available latex agglutination test has a limited sensitivity of 60%. MDL has developed a highly sensitive and specific PCR based assay that can differentiate among the four CV-causing pathogens.

Clinical significance: Chlamydia trachomatis is the causative agent of the disease Chlamydia. It is the most common sexually transmitted bacterial agent. In women it causes cervicitis, urethritis, endometritis and salpingitis. In more complicated cases it may result in tubal scarring, infertility, and ectopic pregnancy. In men it causes urethritis and proctatitis. If left untreated, Chlamydia may develop into lymphogranuloma venereum. Other forms of infection also seen are trachoma, the most preventable form of blindness, and conjunctivitis in neonates. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Cytomegalovirus (CMV) infects 50-80% of Americans by the age of 40. It is known to cause mild or asymptomatic infection in most healthy individuals. The virus is spread from person-to-person through most bodily fluids. Congential infection, which occurs when an infected mother passes the infection along to the fetus, may result in hearing, vision, neurologic and developmental problems shortly after birth. CMV viral shedding can be detected in the vaginal secretions of infected women. The use of molecular techniques, such as Real-Time PCR, enables the clinician to detect this viral shedding thus enabling diagnosis and treatment prior to conception.

Clinical significance: Escherichia coli (E. coli) is the head of the large bacterial family, Enterobacteriaceae, the entericbacteria, which are facultatively anaerobic gram-negative rods that live in the intestinal tracts of animals and humans during both health and disease. The urinary tract is the most common site of infection by E coli. E coli accounts for more than 90% of all uncomplicated UTIs. The recurrence rate after a first E coli infection is 44% over 12 months. E coli UTIs are caused by the uropathogenic strains of E coli. E coli causes a wide range of UTIs, including uncomplicated urethritis/cystitis, symptomatic cystitis, pyelonephritis, acute prostatitis, prostatic abscess, or urosepsis. Uncomplicated cystitis occurs primarily in females who are sexually active and are colonized by a uropathogenic strain of E coli. Subsequently, the periurethral region is colonized from colon contamination, and the organism reaches the bladder during sexual intercourse.

Clinical significance: G. vaginalis can be found as normal vaginal flora in some women. However, significant increases in numbers can cause bacterial vaginosis and urinary tract infections. G. vaginalis infection is a risk factor for premature labor, chorioamionitis, and postpartum endometritis.

110 Treponema pallidum by Real-Time PCR
122 Haemophilus ducreyi by Real-Time PCR
126 Herpes subtype (HSV-1 & HSV-2) by Real-Time PCR

Clinical significance: The three major causes of Genital Ulcer Disease (GUD) in the United States are Herpes simplex virus, Treponema pallidum (syphilis), and Haemophilus ducreyi (chancroid). Currently, the diagnosis of GUD is based primarily on the clinical presentation of the ulcer itself. However, agent-specific diagnosis based solely on clinical evaluations are often obscured by multiple and mixed infections. As treatment options vary, it is medically necessary to identify the causative agent of GUD. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: H. ducreyi is the causative agent of the sexually transmitted disease soft chancre or chancroid. It is most commonly diagnosed in males, probably due to the asymptomatic or inapparent infection that often occurs in females. It typically takes 5-7 days after exposure for symptoms to present, but may take as long as several weeks. A tender, small, solid, raised skin lesion will develop with a red base that may develop into a raised sore containing pus. It may then become an open ulcer within 2 days. These lesions are generally limited to the genitalia or perianal area. The lesion erodes to form a painful ulcer and swelling of lymph nodes in the groin area (bubo) in approximately 50% of patients. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Only performed after a #126 is positive.
Charges will be the total of tests #126 + #113.

Clinical significance: HSV quantitative DNA based assay is performed by quantitative Real-Time PCR. Real-Time PCR is an ultra sensitive assay that utilizes intermolecular controls that coincide with the tested specimen. Evaluation of viral load is essential for patient stratification, predicting clinical outcome, and evaluating disease progression.

Clinical significance: HSV infection is epidemic in the United States. Genital herpes is the most common cause of genital ulcer disease in the developed world. HSV-1 classically presents as herpes gingivostomatitis, an infection of the oral mucosa. It can also cause conjunctivitis, keratitis, and herpetic whitlow. HSV-2 is the most common cause of genital ulcers in the United States. More than 95% of recurrent disease is due to HSV-2. The main application for HSV subtyping is with regard to the clinical issue of recurrent infection. Most painful and annoying recurrent genital herpes is due to HSV-2, and almost all recurrent cold sores or fever blisters are due to HSV-1. However, genital herpes also can be caused by HSV-1. This type of genital herpes is much less frequently recurrent and each recurrence usually lasts only a few days. It has been documented that as many as one third of herpes infections are due to HSV-1, particularly in adolescents and young adults.

Antigen detection systems for HSV are specific and sensitive when applied to the evaluation of genital lesions, but the titer of HSV present during asymptomatic reactivation is 10- to 100-fold less than the titer present during symptomatic episodes. Therefore, methods based on the detection of viral proteins are not likely to be as sensitive as DNA amplification assays. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Human Papillomavirus (HPV) type is a well established risk factor determinant for progression to cervical cancer. To date, over 115 different HPV subtypes have been reported. HPV-16 and HPV-18 are the most common “high risk” HPV types associated with cervical cancer. Together, they only account for about 70% of all cases, a value which is highly variable between clinical studies. While other diagnostic procedures report the HPV infections as either “high risk” or “low risk” for the development of cervical cancer, HPV Type-Detect specifically identifies which actual HPV subtypes are contained within the biological specimen. Additionally, combinations of HPV types are detectable within single specimens, a phenomenon that occurs with significant frequency. Designed using an automated system capable of robotic precision, this highly specific assay can be readily incorporated into diagnostic screening and epidemiological evaluations.

This test has been replaced by Test 140: HPV Type-Detect by PCR. (Oct. 4, 2006)

Clinical significance: Klebsiella pneumoniae is a gram-negative rod-shaped bacterium that belongs to the family Enterobacteriaceae.  It is among the most common bacteria encountered by physicians worldwide and has become a well-recognized cause of nosocomial infections such as pneumonia, urinary tract infections, wound infections and bacteremia in immunocompromised patients. It is a common cause of human urinary tract infection when there are structural abnormalities or urethral medical instrumentation.

105 Chlamydia trachomatis by Real-Time PCR
145 Neisseria gonorrhoeae by Real-Time PCR with reflex to Ciprofloxacin Resistance by Pyrosequencing
111 Trichomonas vaginalis by Real-Time PCR

Clinical significance: Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis are the major causes of leukorrhea. C. trachomatis is the most common sexually transmitted bacterial agent. In women, C. trachomatis causes cervicitis, urethritis, endometritis, and salpingitis. Prolonged C. trachomatis infection may result in tubal scarring, infertility, and ectopic pregnancy. Neisseria gonorrhoeae is the causative agent of the sexually transmitted disease gonorrhea. In women, the most common symptom of N. gonorrhoeae infection is endocervical infection and, if left untreated, may develop into vulvovaginitis and pelvic inflammatory disease. As a protozoan parasite, Trichomonas vaginalis is the causative agent of the sexually transmitted disease trichomoniasis. T. vaginalis infection is the primary cause of vaginitis, cervicitis and urethritis in women. Routine clinical diagnosis usually depends on microscopic identification of the parasite in wet mount preparations, which are only 60% sensitive as compared to culture-positive women. The sensitivity and specificity of PCR testing for C. trachomatis and N. gonorrhoeae are superior to the HCII (probe-based) assay which has a sensitivity/specificity of 75% / 97%, and 90.8% / 99.3%, respectively. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Lymphogranuloma venereum (LGV) is a sexually transmitted Chlamydial disease that should be part of the differential diagnosis for any patient presenting with a genital ulcer and / or inguinal lymphadenopathy. Treatment involves the use of antibiotics to clear the infection and to prevent tertiary sequelae. LGV is caused by C. trachomatis, serotypes L₁, L₂, and L₃. C. trachomatis serovars B and D-K are associated with causing non-gonococcal urethritis and cervicitis. While these other serotypes of C. trachomatis are limited to superficial infection of mucus membranes, serotypes L₁, L₂, and L₃ are more invasive and virulent, and tend to result in systemic disease.

LGV occurs in three distinct stages. The first stage is an incubation period of anywhere from three days to six weeks (10-14 days average) and is characterized by a painless genital papule which usually disappears after a few days. The onset of the second stage occurs two-six weeks later and often manifests as unilateral inguinal lymphadenopathy. Constitutional symptoms, such as fever, chills, malaise, myalgias, and arthralgias, are common in this stage of the disease. The third stage may occur years after the initial infection and is termed genitoanorectal syndrome. Women are more likely to present in this stage. Symptoms include fever, pain, tenesmus, pruritus, and purulent or bloody diarrhea. In this Real-Time PCR assay amplification with high sensitivity and specificity can differentiate between LGV and C. trachomatis serotypes.

Clinical significance: Mobiluncus species are anaerobic bacteria that are commonly associated with Bacterial Vaginosis (BV). It is a leading cause of abnormal vaginal discharge and odor. BV constitutes a massive microecologic alteration of the vaginal flora. It is characterized by: (1) decreased or absent Lactobacillus spp., (2) a logarithmically increased concentration of Gardnerella vaginalis (> 10^8 to 10^11 CFU/g), (3) logarithmically increased concentrations of a set of potentially pathogenic bacteria, including Mobiluncus spp. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Molluscum contagiosum virus (MCV) is a member of the human pox viruses which produces small raised papules or lesions with central umbilications and a white, firm, curd-like core. Infection occurs commonly in children under 5 years due to casual contact and in young adults due to skin-to-skin contact during sexual intercourse. MCV is a common infection in the United States and accounts for approximately 1% of all undiagnosed skin disorders. Many physician’s find it necessary to differentiate MCV from Human Papillomavirus (HPV) or Herpes Simplex virus (HSV) infections, which have greater mortality and mobidity. In this assay, DNA is extracted from a swab sample of lesions actively shedding the virus or biopsies of the actual lesion and subjected to Real-Time PCR amplification.

Clinical significance: Mycoplasmas are small (0.2 – 0.3 nm), membrane-bound organisms capable of independent self-replication. The most prevalent strains recoverable from the genital tract are Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium. Infants can become colonized with genital mycoplasmas during birth. Mycoplasma genitalium has been associated with non-gonoccocal urethritis, acute endometritis, cervicitis, and pelvic inflammatory disease (PID). Genital mycoplasma infections are usually diagnosed by culture. However, due to it’s fastidious slow-growing nature, M. genitalium may take up to 8 weeks to culture. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Mycoplasmas are small (0.2 – 0.3 nm), membrane-bound organisms capable of independent self-replication. The most prevalent strains recoverable from the genital tract are Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium. Infants can become colonized with genital mycoplasmas during birth. M. hominis has been linked to pyelonephritis, pelvic inflammatory disease (PID), spontaneous abortion, and postpartum septicemia and fever. Genital mycoplasma infections are usually diagnosed by culture. However, it can take 2 to 5 days to culture M. hominis. In this assay, DNA is extracted from the specimen and subjected to PCR amplification

Clinical significance: Mycoplasma penetrans, a species of Mycoplasmataceae, infects humans in the urogenital and respiratory tracts. A typical feature of M.penetrans is penetration into human cells. Long-term persistence of M.penetrans in patients has also been documented on the basis of its isolation from urine specimens collected at different times over the period of 1 year from the same children with human immunodeficiency virus (HIV) infection. In human disease, M.penetrans is associated mainly with HIV-1 infection, particularly in adults among the homosexual population in Europe and the USA, and among both homosexual and heterosexual males in South America but has also been suggested to be a primary cause of human disease in non-HIV-related urethritis and respiratory disease.

This test has been replaced by Test 145: Neisseria gonorrhoeae by Real-Time PCR with reflex to Ciprofloxacin Resistance by Pyrosequencing. (Dec. 11, 2006)

Clinical significance: The incidence of drug-resistant strains of Neisseria gonorrhoeae has increased dramatically worldwide. Since 1991, when the first ciprofloxacin resistant strains were isolated, the number of resistant cases has been found to exceed 50% in some Asian countries. Fluoroquinolone-resistant strains are also on the rise in the United States and Canada (CDC STD Surveillance Report 2004). Accordingly, the number of failed treatments has risen, with 500 mg doses of ciprofloxacin demonstrating a 45% failure rate for gonorrheal strains having an MIC greater than 4.0 μg/mL (Gonococcal Isolate Surveillance Report, 2003). Therefore, the CDC currently does not recommend the use of fluoroquinolones for the treatment of gonorrhea acquired in Asia, the Pacific Islands (including Hawaii), England, Wales, California and other locales with increased quinolone-resistant prevalences. MDL is providing, at no additional charge to the client, an analysis of two codons within the DNA gyrase gene for all N. gonorrhoeae positive OneSwab^® and UroSwab^® specimens. Mutations in these regions have been associated with ciprofloxacin resistance and result in the recommendation of an alternative drug treatment. The result of this DNA-based analysis will also be available to the physician significantly faster than conventional culture based methods.

105 Chlamydia trachomatis by Real-Time PCR
145 Neisseria gonorrhoeae by Real-Time PCR with reflex to Ciprofloxacin Resistance by Pyrosequencing

Clinical significance: Genitourinary tract infections due to C. trachomatis and N. gonorrhoeae are a major cause of morbidity in sexually active individuals. In males they may cause epididymitis and urethritis. In females, they can cause pelvic inflammatory disease (PID), ectopic pregnancy, and infertility. If left untreated, Chlamydia may develop into lymphogranuloma venereum and N. gonorrhoeae may develop into a disseminated gonococcal infection (DGI). DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Polyomavirus BK is a member of the Papovavirus family and infects up to 90% of the general population. After primary infection, generally occurring in childhood without evident symptoms, the virus can remain latent in the urinary tract. Reactivation can be enhanced by immunosuppressive conditions, leading to overt clinical disease. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Polyomavirus JC is a double-stranded DNA virus belonging to the Papovavirus family and it is estimated that 60-80% of adults in Europe and the United States have antibodies to JC virus. It is proposed that JC virus establishes a latent infection in the kidney after a primary infection. JC virus has been linked to the development of hemorrhagic cystitis, ureteral stenosis and allograft dysfunction in renal transplant recipients. It is also believed to be the primary causative agent of both nephropathies after transplantation and progressive multifocal leukoencephalopathy. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Proteus mirabilis, a gram-negative enteric bacterium, is one of the most common gram-negative pathogens encountered in clinical specimens and can cause a variety of community or hospital-acquired illnesses, including urinary tract, wound, and bloodstream infections. P. mirabilis is one of the most common causes of urinary tract infections (UTI) in individuals with long-term indwelling catheters, complicated UTI, and bacteremia among the elderly.   Individuals suffering from UTIs caused by P. mirabilis often develop bacteriuria, kidney and bladder stones, catheter obstruction due to stone encrustation, acute pyelonephritis, and fever. In this assay, DNA is extracted from the patient specimen and subjected to PCR amplification.

Clinical significance: T. pallidum is the causative agent of the sexually transmitted disease syphilis. The diagnosis of syphilis is complicated because T. pallidum is one of the few major bacterial pathogens of humans that cannot be cultivated on artificial medium. In this assay, we utilize a sensitive technique for T. pallidum identification that is based upon the amplification of the gene encoding the pathogen-specific and highly conserved 47-kDa membrane immunogen (tpp 47). In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Trichomonas vaginalis is a protozoan parasite. It is the causative agent of the sexually transmitted disease trichomoniasis. It is a major cause of vaginitis, cervicitis, and urethritis in women and may cause nongonococcal urethritis, prostatitis, and perhaps other genitourinary tract syndromes in men. Routine clinical diagnosis usually depends on microscopic identification of the parasite in wet mount preparations. Unfortunately, wet mount examination detects only 60% of culture-positive cases in women. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Ureaplasma, of the family Mycoplasmataceae, are among the smallest free-living bacteria. Colonization, the presence and multiplication of microorganisms without tissue invasion or damage, usually begins at birth with passage through an infected mother’s birth canal. Ureaplasmas have been isolated from the genital tract of 1/3 of infant girls and from the noses and throats of 15% of infant boys and girls. Carriage of these organisms does not usually persist beyond the age of 2. However, a small portion of pre-pubertal children will remain colonized and asymptomatic. As a result of sexual contact, the incidence of genital Ureaplasmas increases after puberty. In some pregnant women, Ureaplasma infections are considered to be the cause of chorioamnionitis and premature delivery. They are frequently transmitted from mothers to their infants, which may cause a variety of disorders including pneumonia, persistent pulmonary hypertension, and chronic infection of the central nervous system. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

551 Candida albicans by Real-Time PCR
557 Candida tropicalis by Real-Time PCR
558 Candida parapsilosis by Real-Time PCR
559 Candida glabrata by Real-Time PCR

Clinical significance: The incidence of Urogenital Candidiasis in men is poorly documented, particularly since it is not a reportable entity. Four major causes of Urogenital Candidiasis in men are Candida albicans. C. glabrata, C. parapsilosis, and C. tropicalis. Candida infection in men can cause urethritis and balanitis, an inflammation of the foreskin and glans of the penis in uncircumcised men. Prostatic infection with Candida has also been reported. Candidosis of the penis can be transmitted during sexual contact with partners with chronic vaginal or anal carriage. MDL has developed a highly sensitive and specific PCR based assay that can differentiate among these four pathogens.

129 Mycoplasma genitalium by Real-Time PCR
130 Mycoplasma hominis by Real-Time PCR

Clinical significance: Mycoplasmas are small (0.2 – 0.3 nm), membrane-bound organisms capable of independent self-replication. The most prevalent strains recoverable from the genital tract are Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium. Infants can become colonized with genital mycoplasmas during birth. After puberty, colonization with mycoplasmas occurs primarily through sexual contact. Genital mycoplasmas are commonly isolated from gravid women at approximately the same recovery rate as in nonpregnant women with the same degree of sexual activity. Mycoplasmas and Ureaplasmas are strongly associated with infertility, intraamnionic infection, postpartum infection, pelvic inflammatory disease (PID), and histologic chorioamnionitis. Genital mycoplasma infections are usually diagnosed by culture. However, it can take from 2 to 5 days or up to 8 weeks to culture. Subspeciation of human urogenital mycoplasma infections is paramount for successful antimicrobial therapy due to differential antimicrobial susceptibilities. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

129 Mycoplasma genitalium by Real-Time PCR
130 Mycoplasma hominis by Real-Time PCR
320 Ureaplasma urealyticum by Real-Time PCR

Clinical significance: Mycoplasmas are small (0.2 – 0.3 nm) membrane bound organisms capable of independent self-replication. The most prevalent strains recoverable from the genital tract are Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium. Infants can become colonized with genital mycoplasmas during birth. After puberty, colonization with mycoplasmas occurs primarily through sexual contact. Genital mycoplasmas are commonly isolated from gravid women at approximately the same recovery rate as in nonpregnant women with the same degree of sexual activity. Mycoplasmas and Ureaplasmas are strongly associated with infertility, intraamnionic infection, postpartum infection, pelvic inflammatory disease (PID), and histologic chorioamnionitis. Genital mycoplasma infections are usually diagnosed by culture. However, it can take from 2 to 5 days or up to 8 weeks to culture. Subspeciation of human urogenital mycoplasma infections is paramount for successful antimicrobial therapy due to differential antimicrobial susceptibilities. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

This test is for patients that are penicillin-allergic and sensitivities are required.

Only performed after a #127 is positive.
Charges will be the total of tests #127 + #137.

Clinical significance: The typical treatment for these patients is penicillin G of which there is no known resistance. However, up to 12% of the population reports allergies to penicillin. Therefore the macrolide (erythromycin) or lincosamide (clindamycin) classes of drugs need to be administered, particularly for those patients who are at high risk for anaphylactic shock. Previous reports cite an increase in resistance of GBS to erythromycin and clindamycin. For instance, in 2003, resistance to erythromycin and clindamycin was reported as high as 37% and 17%, respectively.

The antibiotic resistance mechanisms are most commonly caused by three genes: ermB, ermTR, and mefA. MDL concluded a study where both the Clinical and Laboratory Standards Institute (formerly NCCLS) 2003 “Performance Standards for Antimicrobial Susceptibility Testing” protocols and a multiplex PCR assay were used to screen for the prevalence of these genes in 222 GBS clinical isolates.

These isolates were obtained from MDL’s clinical swab samples. Of the 222 GBS clinical isolates, 84 strains (38%) were resistant to erythromycin and 46 strains (21%) were resistant to clindamycin. The multiplex PCR proved to be an efficient method to identify the three major antibiotic resistance genes in GBS. With the presence of these genes on mobile genetic elements, such as plasmids and/or transposons, the passing of these genes from bacteria to bacteria is likely and should be monitored to provide the physician with the vital information needed for proper patient treatment.

MDL has developed a highly sensitive and specific multiplex polymerase chain reaction to identify GBS antibiotic resistance genes from GBS clinical isolates.

Clinical significance: Group-B Streptococcus is a common cause of neonatal septicemia, pneumonia and meningitis. It is the most common cause of life-threatening infection in newborns. One out of every twenty babies with GBS dies from the infection. In pregnant women, it can cause bladder infections, womb infections, and stillbirth. Many adults are asymptomatic carriers of GBS in the bowel, vagina, bladder or throat. Diagnosis by traditional cultures may take several days to complete. Once diagnosed, GBS can be treated with antibiotics to prevent the spread from mother to baby.

Clinical significance: Varicella Zoster Virus (VZV), also known as HHV3, is a member of the neurotrophic alpha herpesvirus family, which is considered to be the most infectious of the human herpes viruses. The alpha herpesviruses' possess factors that increase their infectivity, including short reproductive cycles, the ability to replicate in multiple cell types, and the ability to induce high levels of host cell tissue destruction quite rapidly. Humans serve as the alpha herpesviruses' only natural reservoir, which means transmission is person-to-person via an airborne route that involves the aerosolization of virus in nasopharyngeal secretions or more directly by contact with vesicle fluids or respiratory secretions. Primary infections result in chickenpox and 95% occur during childhood. Presenting symptoms include rash, low grade fever, headaches and malaise. Patients with chickenpox remain infective until the last skin lesion has dried and crusted over. Those who are infected during adulthood experience a greater number of complications and account for nearly half of all chickenpox-related deaths. Neonates and pregnant women are particularly susceptible to severe primary VZV infections. Complications associated with VZV infection include bacterial superinfections of the skin and lower respiratory tract. Diagnosis is typically based on clinical presentation, but in some instances, particularly immunocompromised individuals, clinical evaluation is necessary. Because VZV is capable of establishing a latent state within the sensory ganglia, infection is life-long and viral reactivation in the form of shingles or Ramsay Hunt Syndrome is possible at any age. Shingles occur in approximately 20% of the adult population at least once in their lives, with 1% experiencing multiple reactivations. Vaccination with the live attenuated Oka strain of VZV, Varivax, is available and recommended for adults over the age of sixty for the prevention of shingles.

Clinical significance: Adenoviruses cause a number of self-limiting but often highly infectious diseases that affect multiple organs, most commonly those associated with the respiratory and genitourinary tracts. They are non-enveloped icosahedral particles that contain double-stranded DNA. Adenovirus is a relatively harmless pathogen in healthy individuals, but can cause a variety of symptoms in young children and the immunocompromised. Transmission can occur from direct person-to-person contact, or through contact with a contaminated surface or object. Adenovirus is usually asymptomatic, and may cause a variety of symptoms including respiratory problems, gastroenteritis, pink eye, pharyngoconjunctival fever, skin rashes, and genitourinary tract infections including cervicitis, urethritis, and hemorrhagic cystitis. The most severe cases of adenovirus infection may result in pneumonia, croup, and bronchitis. In this assay DNA is extracted from the patient specimen and subjected to PCR amplification.

Clinical significance: Colorado tick fever is an acute viral infection transmitted from the bite of an infected Dermacentor andersoni (wood) tick, and in rare instances by blood transfusion. It is found most commonly in the western United States and Canada, with particular concentration in the mountainous regions of Colorado and Idaho. This disease most commonly develops from March to September, with the highest numbers of infections occurring in May and June. Symptoms start about 3 to 6 days after the tick bite. Symptoms of a two-staged illness present with initial fever for 3 days, resolve, and then return 1 to 3 days later for another few days. Infection can be severe in young children resulting in hospitalization. Possible complications include ascetic meningitis, encephalitis and hemorrhagic fever. In this assay DNA is extracted from the specimen and subjected to PCR amplification.

Cytomegalovirus (CMV), a member of the herpesvirus family, infects 50-85% of adults in the United States prior to age 40. CMV is also found throughout the world, and is transmitted by person-to-person contact through infected body fluids such as saliva, blood, breast milk, and urine. The virus can also be vertically transmitted from mother to child. In most infected individuals, the virus remains dormant and does not cause any significant health issues. However, infection of pregnant women, individuals who work with infants and small children, and immunocompromised patients can be more serious. When symptoms do arise, they usually consist of a mononucleosis-like syndrome along with prolonged fever and hepatitis. In this assay DNA is extracted from the patient specimen and subjected to PCR amplification.

Serum required

Clinical significance: Antibody to viral capsid antigen (VCA) is the most valuable of the EBV specific antibody tests. IgM-VCA appears early in infection and typically disappears within 4-6 weeks. IgG-VCA appears in late acute phase, peaks at 2 to 4 weeks after onset of infection, and may persist throughout a patient’s lifetime. The presence of VCA-IgM antibody with the absence of antibody to EBNA after at least 4 weeks of infection is suggestive of primary infection. Past infection (4-6 months earlier) is usually determined by the presence of both VCA antibodies and EBNA antibodies. Differentiation of the VCA IgG and IgM antibodies is also useful for confirmation when the Monospot test is negative. Susceptibility to EBV infection is also determined by the absence of antibodies to viral capsid antigens.

Clinical significance: EBV is the causative agent of infectious mononucleosis, which occurs primarily in late adolescence and early adulthood. It is characterized by malaise, fever, hepatosplenomegally, lymphadenopathy, and abdominal discomfort. EBV has also been associated with post-transplant lymphoma, Burkitt’s lymphoma, and nasopharyngeal carcinoma. Reactivations of this disease are suspected in chronic fatigue syndrome. EBV is one of the most common human viruses. It is estimated that worldwide as many as 80% to 90% of all adults have at one time been infected. Although it is normally a self-limiting infection, complications can occur, such as splenomegaly, hepatitis, pericarditis, or central nervous system involvement. In certain rare instances it may be fatal. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

This test has been replaced by Test 260: Hepatitis B Virus (HBV) viral load by Real-Time PCR. (Jan. 29, 2007)

Clinical significance: Hepatitis A Virus (HAV) is an enterovirus transmitted by the orofecal route. It causes an acute form of hepatitis, but does not have a chronic stage and will not cause any permanent damage to the liver. Only 3 out of 4 people with HAV have symptoms. The symptoms may include: jaundice, nausea, fatigue, and vomiting. In 1991, the Centers for Disease Control (CDC) reported a low mortality rate of 0.004% for the general population. For those aged 50 and over, the rate jumps to 0.0175%. There is no specific treatment for HAV. The best preventions against HAV are the commercially available vaccines, as well as good hygiene and sanitary conditions. In order to facilitate an accurate diagnosis of this disease, a Real-Time polymerase chain reaction (PCR) based test capable of detecting HAV has been developed.

This test has been replaced by Test 260: Hepatitis B Virus (HBV) viral load by Real-Time PCR. (Jan. 29, 2007)

Clinical significance: Hepatitis B Virus (HBV) is implicated in hepatocellular carcinoma and cirrhosis. HBV infections represent a major public health problem because of the ability of HBV to cause a chronic carrier state. The spectrum of infection can range from primary, self-limiting infection that resolves, to a persistent, chronic infection that may remain throughout a person’s lifetime. Current diagnostic methods rely on serum HBV antigen or direct visualization of the virus in serum by electron microscopy. These techniques, however, lack the sensitivity to detect low levels of viremia. The Real-Time PCR amplification method is used to detect HBV in serum/plasma with a marked increase in sensitivity. In this assay, DNA is extracted from the specimen and subjected to Real-Time PCR amplification.

Real-Time PCR is an ultra sensitive assay that utilizes intermolecular controls, which coincide with the tested specimen. Quantifying the presence of HBV aids the clinician in patient stratification and therapeutic monitoring. A positive result should be considered in conjunction with clinical presentation and additional established clinical tests.

Only performed after #250 is positive.
Charges will be the total of tests #250 + #252.

Clinical significance: Hepatitis C Virus (HCV) causes liver disease and is passed through contact with infected blood or blood products. HCV is the leading cause of cirrhosis, increased risk of liver cancer, and the most common reason for liver transplants in the United States. HCV pyrosequencing is useful in determining the genotype of a patient sample. The genotyping result may predict interferon response, and disease progression, and can be used to determine the suitability of treatment.

Clinical significance: Hepatitis C Virus (HCV) causes liver disease and is passed through contact with infected blood or blood products. HCV is the leading cause of cirrhosis, increased risk of liver cancer, and the most common reason for liver transplants in the United States. This assay is useful in determining the viral load of a patient sample. This test can assist clinicians as a confirmation assay once an individual has tested positive by a first-tier assay, or can be used to monitor the suitability for and subsequent length of antiviral HCV drug treatment.

Serum required

Clinical significance: HSV-1 classically presents as herpes gingivostomatitis, an infection of the oral mucosa. It can also cause conjunctivitis, keratitis, and herpetic whitlow. Almost all recurrent cold sores or fever blisters are due to HSV-1. However, genital herpes also can be caused by HSV-1. HSV has been isolated from virtually all visceral or mucocutaneous sites. HSV infections can affect the central nervous system causing aseptic meningitis, HSV encephalitis, and autonomic radiculopathy. Visceral HSV infections include esophagitis, pneumonitis, and disseminated infection. Definitive diagnosis of herpes infections is fundamental to the management of patients and the development of strategies to prevent transmission to partners and neonates. Detection of antibodies allows diagnosis of an infection when other methods such as culture or antigen detection are impractical or yield negative results.

Serum required

Clinical significance: The most painful and annoying recurrent genital herpes is due to HSV-2. It can also cause conjunctivitis, keratitis, herpetic whitlow, and herpes gingivostomatitis, an infection of the oral mucosa. HSV has been isolated from virtually all visceral or mucocutaneous sites. HSV infections can affect the central nervous system causing aseptic meningitis, HSV encephalitis, and autonomic radiculopathy. Visceral HSV infections include esophagitis, pneumonitis, and disseminated infection. Definitive diagnosis of herpes infections is fundamental to the management of patients and the development of strategies to prevent transmission to partners and neonates. Detection of antibodies allows diagnosis of an infection when other methods such as culture or antigen detection, are impractical or yield negative results.

Clinical significance: HSV infection is epidemic in the United States. Genital herpes is the most common cause of genital ulcer disease in the developed world. HSV-1 classically presents as herpes gingivostomatitis, an infection of the oral mucosa. It can also cause conjunctivitis, keratitis, and herpetic whitlow. HSV-2 is the most common cause of genital ulcers in the United States. More than 95% of recurrent disease is due to HSV-2. The main application for HSV subtyping is with regard to the clinical issue of recurrent infection. Most painful and annoying recurrent genital herpes is due to HSV-2, and almost all recurrent cold sores or fever blisters are due to HSV-1. However, genital herpes also can be caused by HSV-1. This type of genital herpes is much less frequently recurrent and each recurrence usually lasts only a few days. It has been documented that as much as one third of herpes infections are due to HSV-1, particularly in adolescents and young adults.

Antigen detection systems for HSV are specific and sensitive when applied to the evaluation of genital lesions, but the titer of HSV present during asymptomatic reactivation is 10- to 100-fold less than the titer present during symptomatic episodes. Therefore, methods based on the detection of viral proteins are not likely to be as sensitive as DNA amplification assays. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Serum required

Clinical significance: Human Herpes Virus 6 is a member of the Herpesviridae family. HHV-6 isolates are classified into two variants, A and B. Although the two variants are very closely related, they have distinct differences in immunologic, biologic, epidemiologic, and molecular properties. Studies indicate that HHV-6 infects nearly all humans by 2 years of age. Although very valuable, serological studies do not differentiate between variants A and B.

Clinical significance: Human Herpes Virus 6 (HHV-6) is a member of the Herpesviridae family. HHV-6 isolates are classified into two variants, A and B. Although the two variants are very closely related, they have distinct differences in immunologic, biologic, epidemiologic, and molecular properties. HHV-6 variant B is the causative agent of the common childhood illness Roseola. HHV-6 variant B has also been associated with Multiple Sclerosis (MS) and other neurological disorders. Variant A is implicated in patients suffering from mononucleosis and HIV. A subset of individuals with chronic fatigue syndrome exhibit HHV-6 variant A infection. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: HHV-7 is a member of the T-lymphotropic beta herpesviruses and is closely related to HHV-6 and cytomegalovirus (CMV). Roseola infantum occurs in infant and young children populations as a result of primary infection. Infections typically last for approximately six days and are typified by a rash on the neck and trunk, mild upper respiratory infection and swollen glands. A common infection, typically occurring by the age of five in 95% of the population, HHV-7 lies in a latent state, reemerging when the host immune system is compromised. Reemergence levels have been reported to be as high as 45% in liver transplant recipients and elevated in bone marrow transplant recipients. A report by Osman et al. in 1996 revealed active HHV-7 infections correlated with increased risk of developing CMV disease, evidence that is further bolstered by the study that linked HHV-6 and HHV-7 reactivation within transplant recipients with their interaction with CMV. Clinical manifestations of reactivated virus have only been linked with the development of encephalitis in bone marrow transplant recipients and with hepatitis in liver transplant recipients. Due to the high prevalence of infection, serologically testing is not a useful means of determining reactivation status. Viral culturing is discourage because it takes too long and increases the likelihood of a possible HHV-7 mediated CMV reactivation. Real-Time PCR assays are considered to be the most appropriate diagnostic tool as it is a fast and reliable method that can also serve as a means of determining viral load. In this assay, DNA is extracted from the patient specimen and subjected to PCR amplification.

Clinical significance: HHV-8, also known as Kaposi’s sarcoma-associated Herpes virus (KSHV), is the most recently discovered human tumor virus. Virtually all Kaposi’s sarcoma lesions are HHV-8 positive. It is associated with HIV infection, immunosuppressed patients, as well as endemic Kaposi’s sarcoma areas in Africa, Eastern Europe, and the Mediterranean basin. HHV-8 encodes genes that can modulate cellular growth properties and possibly play a role in disease progression. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Clinical significance: Human immunodeficiency virus (HIV) is the causative agent of the acquired immunodeficiency syndrome (AIDS). This virus is transmitted via sexual contact, exposure to contaminated blood and blood products, or transmitted from an infected mother to her fetus. This assay quantifies the number of HIV-1 copies in patient blood. This test is not recommended for diagnosis of HIV infection, viral antibody screening (Test 253) is still the preferred method.  Viral load monitoring is useful in establishing the viral baseline prior to initiating antiviral therapy, monitoring the efficacy of chosen antiviral regimens and for the emergence of drug-resistance particles, and in determining the progression of infection.

Clinical significance: A major causative agent of the acquired immunodeficiency syndrome (AIDS) is human immunodeficiency virus 1 (HIV 1). This virus is transmitted via sexual contact, exposure to contaminated blood and blood products, or transmitted from an infected mother to her fetus. In this assay, antibodies to HIV-1 are detected.

Clinical significance: Human immunodeficiency virus (HIV) is the causative agent of the acquired immunodeficiency syndrome (AIDS). This virus is transmitted via sexual contact, exposure to contaminated blood and blood products, or transmitted from an infected mother to her fetus. In this assay, antibodies to HIV-1 and HIV-2 are both detected. However, this assay will not distinguish between HIV-1 and HIV-2.

Clinical significance: HTLV was the first human oncogenic retrovirus to be identified. It is the causative agent of adult T-cell leukemia-lymphoma and tropical spastic paraparesis or HTLV-I associated myelopathy (HAM/TSP). HTLV infection is endemic to the islands of southwestern Japan, the Caribbean basin including the West Indies, northern South America, the southeastern U.S., Central and west Africa, Melanesia, the Middle East, and India. HTLV is thought to be transmitted sexually, through contact with blood, vertically from mothers to their fetus, and through breast milk. Available evidence indicates that infection is probably life long and asymptomatic in most individuals. The HTLV viruses potentiate and activate the expression of HIV in vitro and in human populations, and may accelerate disease progression. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: La Crosse virus is the causative agent of La Crosse encephalitis. This vector-borne disease is transmitted through the bite of an infected Aedes triseriatus tree hole mosquito. Laboratory confirmed cases of La Crosse virus occur with decreasing frequencies from North to South.  The vast majority of infections also occur in the eastern half of the United States. LAC is traditionally active in the upper Midwest and Great Lakes areas; however, in recent years there has been an increase in frequency in the Mid-Atlantic States. Although LAC infection is more common in children under 15 years of age, it can also cause encephalitis in immunosuppressed adults. It is also more common in males. Most LAC infections are subclinical. However, when symptoms are evident the onset is abrupt. LAC virus produces an acute encephalitis that begins with a mild fever and illness lasting on average 1 to 3 days and sometimes persisting for up to one week. Patients typically present with fever, chills, abdominal pain, and headache with or without photophobia. One can also experience upper respiratory symptoms with or without sore throat as well as cough. More serious illness can occur with the presence of vomiting, nuchal rigidity, lethargy and coma.

Clinical significance: Human Parvovirus B19, first recognized in 1975, causes a variety of disease syndromes determined by the age and hematological status of the host. In healthy individuals, it causes erythema infectiosum, also known as fifth disease. In women, in particular, the rash illness is accompanied by arthritis. In subjects with hemolytic anemia, a more profound anemic episode occurs, with transient loss of erythrocyte precursors from the bone marrow. It is commonly associated with immunocompromised individuals. B19 infection should be considered as part of the differential diagnosis in any patient presenting with an acute polyarthritis. In contrast to rheumatoid arthritis, B19 infection is not associated with joint destruction. However, differentiation between early rheumatoid arthritis and B19 arthropathy is important because the immunosuppressive therapy prescribed for rheumatoid arthritis is not indicated in Parvovirus B19 infection. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Polyomavirus JC is a double-stranded DNA virus belonging to the Papovavirus family, and it is estimated that 60-80% of adults in Europe and the United States have antibodies to JC virus. It is proposed that JC virus establishes a latent infection in the kidney after a primary infection. JC virus has been linked to the development of hemorrhagic cystitis, ureteral stenosis and allograft dysfunction in renal transplant recipients. It is also believed to be the primary causative agent of both nephropathies after transplantation and progressive multifocal leukoencephalopathy. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: St. Louis Encephalitis virus (SLE) is a flavivirus capable of inducing aseptic meningitis or encephalitis in infected individuals. Transmission is via a bite from an infected mosquito and can occur anywhere within the continental United States, though the CDC reports the highest prevalence in Indiana, Illinois, Mississippi, Ohio and Texas. The incubation period is typically from five to fifteen days. Symptoms range from mild, limited to fever and headache, to severe, marked by headache, high fever, disorientation, stupor, neck stiffness and occasional convulsion and paralysis. Hospitalization for CNS infection occurs for 95% of recognized cases with a reported 3% to 30% mortality rate. There is no specific treatment for SLE and no available vaccine. In this assay, DNA is extracted from the patient specimen and subjected to PCR amplification.

Clinical significance: Varicella Zoster Virus (VZV), also known as HHV3, is a member of the neurotrophic alpha herpesvirus family, which is considered to be the most infectious of the human herpes viruses. The alpha herpesviruses possess factors that increase their infectivity, including short reproductive cycles, the ability to replicate in multiple cell types, and the ability to induce high levels of host cell tissue destruction quite rapidly. Humans serve as the alpha herpesviruses' only natural reservoir, which means transmission is person-to-person via an airborne route that involves the aerosolization of virus in nasopharyngeal secretions or more directly by contact with vesicle fluids or respiratory secretions. Primary infections result in chickenpox and 95% occur during childhood. Presenting symptoms include rash, low grade fever, headaches and malaise. Patients with chickenpox remain infective until the last skin lesion has dried and crusted over. Those who are infected during adulthood experience a greater number of complications and account for nearly half of all chickenpox-related deaths. Neonates and pregnant women are particularly susceptible to severe primary VZV infections. Complications associated with VZV infection include bacterial superinfections of the skin and lower respiratory tract. Diagnosis is typically based on clinical presentation, but in some instances, particularly immunocompromised individuals, clinical evaluation is necessary. Because VZV is capable of establishing a latent state within the sensory ganglia, infection is life-long and viral reactivation in the form of shingles or Ramsay Hunt Syndrome is possible at any age. Shingles occur in approximately 20% of the adult population at least once in their lives, with 1% experiencing multiple reactivations. Vaccination with the live attenuated Oka strain of VZV, Varivax, is available and recommended for adults over the age of sixty for the prevention of shingles.

West Nile Virus (WNV) is spread most often by infected mosquitoes. In 1999, the CDC reported that there were 62 human cases of WNV infection in New York State. Since then, this flavivirus has rapidly spread throughout the continental United States—in 2005, the CDC reported 2,949 human cases of WNV infection. Although about 80% of infected people show no symptoms upon infection, the remainder exhibit mild symptoms such as fever, headache, body aches, nausea and vomiting. Symptoms typically present generally 3 to 14 days post infection. In about 1 out of 150 infected people, symptoms are much more severe and range from high fever, neck stiffness, stupor and disorientation to coma, tremors, convulsions, muscle weakness, vision loss, numbness, and even paralysis. Real-time PCR is most successful for detection when utilized immediately after infection. Subsequently, serological assays are available to determine exposure to WNV.

Clinical significance: Bacteroides ureolyticus is an obligate, aneareobic, gram-negative rod that was first described in clinical specimens in 1948. It is the most frequently isolated Bacteroides species, after Bacteroides fragilis. It has been isolated from mixed cultures of infections involving nearly every organ system in humans. It is associated with ulcerative lesions of both the external and internal genitalia including  the perineal area, and abscesses. It is also a pathogen of the urinary tract. It has been implicated in non-gonoccocal urethritis (NGU).  One study detected B. ureolyticus in 50% of men with NGU. It is thought to cause damage to the urethral mucosa via an endotoxin. In this assay, DNA is extracted from the patient specimen and subjected to PCR amplification.

Clinical Significance: The genus Bartonella contains aerobic, fastidious, gram-negative bacteria that belong to the alpha-2 subgroup of the class Proteobacteria. Due to the limited distribution of its vector, the sand fly, Bartonella bacilliformis is found predominantly at high elevations in the Andes mountains. It is the causative agent of Carriõn’s disease. This biphasic syndrome is comprised of two disorders. Orroya fever is characterized by an acute septicemic phase of severe hemolytic anemia. The chronic form, verruga peruana, is the second phase. It is characterized by reddish papular skin lesions that are highly vascular in nature. Verruga peruana is very similar to bacillary angiomatosis which is caused by B. henselae. Without appropriate antimicrobial therapy, they may be fatal. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: The genus Bartonella contains aerobic, fastidious, gram-negative bacteria that belong to the alpha-2 subgroup of the class Proteobacteria. Bartonella clarridgeiae is predominantly associated with infection in cats. However, it has been documented as an additional cause of Cat Scratch Disease (CSD) along with Bartonella henselae. Transmission from cats to humans has also been documented. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: The genus Bartonella contains aerobic, fastidious, gram-negative bacteria that belong to the alpha-2 subgroup of the class Proteobacteria. Bartonella elizabethae has been associated with endocarditis. The means of transmission of B. elizabethae is unknown, but is believed to be via an arthropod vector. It has been isolated in a human patient and in rats. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: B. henselae is the causative agent of Cat Scratch Disease (CSD) as well as other conditions. It is commonly seen in immunocomprimised patients, particularly those suffering from HIV infection. The classic clinical presentation of CSD is a self-limiting regional lymphadenopathy, usually caused by a cat scratch or bite. The disease starts with a lesion at the site of infection, which may become a papule. Transmission of the disease has been linked to cats and is also suspected to occur via fleas and ticks. Recently, Bartonella has been detected in immunocompromised patients as well as in Ixodes scapularis ticks, the same ticks that transmit Lyme disease. Evidence is mounting that Bartonella species are also transmitted from ticks to humans and can contribute to the disease manifestations of Lyme disease. Proper identification is essential such that the necessary treatments are administered. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical Significance: The genus Bartonella contains aerobic, fastidious, gram-negative bacteria that belong to the alpha-2 subgroup of the class Proteobacteria. B. quintana was first identified as an important human pathogen during World War I when it caused epidemics of louse-borne trench fever. B. quintana infections were rarely recognized from the end of World War II until the 1980s, when the organism re-emerged as an opportunistic pathogen among HIV-infected persons. It has since been identified in bacillary angiomatosis, endocarditis, bacteremia, isolated from AIDS patients, and more recently in homeless populations. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

This test has been replaced by Test 356: Bartonella Species by Real-Time PCR. (Aug. 17, 2007)

Clinical significance: The genus Bartonella contains aerobic, fastidious, gram-negative bacteria which belong to the alpha-2 subgroup of the class Proteobacteria. Our methodology permits the detection and identification of Bartonella henselae and B. quintana. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Pertussis, commonly known as whooping cough, results from an upper respiratory tract infection with Bordetella pertussis. This infection was a significant cause of childhood morbidity and mortality in the early part of the twentieth century and reemerged as a significant health concern in the late 1990’s. The upward trend in childhood pertussis cases has been primarily contributed to decreased vaccine usage, while the increase in adult pertussis cases is contributed to waning vaccine-induced immunity and the lack of a vaccine approved for use in adults. In the assay, we detect IgG and IgA antibodies to B. pertussis in human serum.

Clinical Significance: Brucellosis is an important zoonosis of public health in many countries. Due to the fact that clinical presentation of this disease varies so greatly, diagnosis can really only be made based on laboratory methods. Brucella melitensis is the species that primarily causes infection in humans. Human brucellosis, also known as ‘undulant fever’ or ‘Bang’s disease’ can change from an occupational disease for farmers, veterinarians, and other animal health professionals to a food-borne disease when people consume non-pasteurized milk and cheeses made with raw milk from infected cattle. Human symptoms of brucellosis infection include fever, night sweats, undue fatigue, anorexia, weight loss, headache, and arthralgia. Our PCR-based testing permits the identification of four species of Brucella—Brucella abortus, B. melitensis, B. ovis, and B. suis. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Chlamydophila are obligate intracellular parasites. Chlamydophila pneumoniae, also known as TWAR, is the most recently identified of the Chlamydophila species. It is a common cause of infection throughout the world. Although first isolated in 1965, it was not established as a human pathogen until it was obtained from a respiratory specimen in 1983. Infection is spread via exposure to respiratory secretions. It has been associated with community acquired acute respiratory infection, adult onset asthma, atherosclerotic cardiovascular disease, arthritis, and chronic fatigue syndrome.

Serum required

Clinical Significance: Chlamydophila pneumoniae seropositivity rates are very low in children under 5 years of age. By the time most people reach early adulthood, 50% are seropositive with rates reaching approximately 75% in the elderly. C. pneumoniae specific IgM antibodies appear approximately 3 weeks after onset of illness; whereas, C. pneumoniae-specific IgG antibodies begin to appear about 6-8 weeks after onset. Detection of antibodies allows diagnosis of an infection when other methods, such as culture or antigen detection, are impractical or yield negative results.

Clinical significance: There are three subtypes associated with causing disease in humans. C. pneumoniae causes pneumonia, sinusitis, bronchitis, pharyngitis and has been associated with adult onset asthma, atherosclerotic cardiovascular disease, arthritis, and chronic fatigue syndrome. C. trachomatis is a sexually transmitted disease that also causes conjunctivitis, pneumonia, proctitis, and lymphogranuloma venerium. It is also the cause of ocular trachoma, the leading cause of preventable blindness. Sensitive screening methods are necessary for early detection of Chlamydial infections. Rapid treatment could control and decrease the spread of the disease. MDL has developed a rapid and sensitive PCR-based method for the simultaneous detection and differentiation of Chlamydia sub-species from specimens. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Chlamydia trachomatis is the causative agent of the disease Chlamydia. It is the most common sexually transmitted bacterial agent. In women it causes cervicitis, urethritis, endometritis and salpingitis. In more complicated cases it may result in tubal scarring, infertility, and ectopic pregnancy. In men it causes urethritis and proctatitis. If left untreated, Chlamydia may develop into lymphogranuloma venereum. Other forms of infection also seen are trachoma, the most preventable form of blindness, and conjunctivitis in neonates. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Five subspecies of Francisella are found in the Northern hemisphere, but only F. tularensis subsp. tularensis and subsp. holarctica cause disease in humans. F. tularensis is the causative agent of tularemia, a zoonotic disease of humans, rabbits, rodents, and hares. It is typically transmitted by inhalation, the bite of an infected tick, contact with infected animal products or by the ingestion of contaminated water. Clinical manifestations of tularemia vary depending on the virulence of the strain and the route of inoculation. Inhalation results in the pneumonic form. Acquisition through a tick bite or from contact with an infected animal, results in the ulceroglandular form of the disease. Francisella can also be contracted through the conjuctiva, causing the oculoglandular form of tularemia. Less commonly, ingestion of contaminated foods or water may result in clinical symptoms. Once the bacterium enters the body, it travels to the draining lymph nodes and then spreads to the liver, lungs, and spleen of infected humans or animals, where it replicates to high numbers. In this assay DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Helicobacter pylori resides within the mucous membrane of the gastric epithelium and occasionally the duodenal or esophageal mucosal epithelium as well. It can lead to inflammation of the mucosa and, if untreated, chronic superficial gastritis. This inflammation process has been linked to peptic ulceration and gastric cancer. Helicobacter pylori is now established as the most common cause of gastritis. In this procedure, we perform a PCR assay for the sensitive and specific detection of H. pylori. The assay is based on the DNA sequence of a species-specific protein antigen, which is present in all strains of H. pylori tested, and whose coding sequence did not hybridize to the DNA of numerous enteric bacteria. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Infection with Helicobacter pylori is the leading cause of gastric cancers. It can also present clinically as a variety of gastrointestinal diseases including duodenal and gastric ulcers, malt lymphoma, gastric cancer and non-gastric dyspepsia. With approximately 50% of the world’s population colonized with this organism, concern for the diagnosis and subsequent treatment of H. pylori infection is growing. Some diseases not associated with the gastrointestinal tract (i.e. liver disease, acne rosacea, chronic urticaria, atherosclerosis, and iron deficiency anemia) may be associated with H. pylori infection. Infection by H. pylori can also lead to loss of normal gastric function, including the ability to absorb micronutrients such as Vitamin B12, folic acid, beta-carotene and iron. In the assay, we detect IgG and IgA antibodies to H. pylori in human serum.

Clinical significance: L. pneumophila, a rod-shaped, gram negative bacterium, is the causative agent of Legionella, also referred to as Legionnaire's disease, and Pontiac fever. Legionella pneumophila is involved in more than 95% of cases of severe atypical pneumonia. This disease is most often contracted by inhaling mist from L. pneumophila contaminated water sources. Thus far, no cases of person-to-person transmission have been documented. It is commonly seen in immunocomprimised patients, transplant patients, and people with impaired pulmonary function, such as heavy smokers. Traditional isolation of the organism from bronchoalveolar lavage (BAL) specimens is very invasive and time consuming. In addition, it has been demonstrated that certain strains cannot be cultured. Traditional serological means of diagnosis is often difficult due to the delay in seroconversion with respect to timing of the onset of illness. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Mycoplasmas are small (0.2 – 0.3 nm), membrane-bound organisms capable of independent self-replication. The most prevalent strains recoverable from the genital tract are Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium. Infants can become colonized with genital mycoplasmas during birth. M. hominis has been linked to pyelonephritis, pelvic inflammatory disease (PID), spontaneous abortion, and postpartum septicemia and fever. Genital mycoplasma infections are usually diagnosed by culture. However, it can take 2 to 5 days to culture M. hominis. In this assay, DNA is extracted from the specimen and subjected to PCR amplification

Clinical significance: Mycoplasma species are the smallest and genetically simplest self-replicating bacteria. Mycoplasma species are ubiquitous in nature and are widely distributed throughout the animal kingdom. They have recently been associated with certain acute and chronic illnesses. They can function as causative agents, cofactors, and opportunistic infections. M. penetrans has been isolated from the urogenital tract and from HIV patients. It is a potential cofactor in AIDS progression. Mycoplasmas have been associated with respiratory illness, urogenital disease, immunosuppressive disease such as HIV infection, cardiac diseases, arthritic syndromes, tick-borne illness, and chronic fatigue syndrome. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: T. pallidum is the causative agent of the sexually transmitted disease syphilis. The diagnosis of syphilis is complicated because T. pallidum is one of the few major bacterial pathogens of humans that cannot be cultivated on artificial medium. Syphilis progresses in stages. The initial infection manifests as a lesion or chancre at the site of inoculation. The second stage consists of flu-like symptoms, anorexia, swelling of the lymph nodes, and a generalized rash of the mucous membranes and skin that usually appears as brown sores roughly the size of a penny. The palms of the hands and soles of the feet are almost always covered by the rash. If untreated, syphilis may lapse into a latent stage during which the disease is no longer contagious and no symptoms are present. Late syphilis can cause the destruction of virtually any organ or tissue including the heart, eyes, brain, nervous system, bones, and joints. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Ureaplasma, of the family Mycoplasmataceae, are among the smallest free-living bacteria. Colonization, the presence and multiplication of microorganisms without tissue invasion or damage, usually begins at birth with passage through an infected mother’s birth canal. As a result of sexual contact, the incidence of genital Ureaplasmas increases after puberty. In some pregnant women, Ureaplasma infections are considered to be the cause of chorioamnionitis and premature delivery. They are frequently transmitted from mothers to their infants, which may cause a variety of disorders including pneumonia, persistent pulmonary hypertension, and chronic infection of the central nervous system. It has also been associated with infectious or septic arthritis. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

The genus Yersinia encompasses a group of gram-negative, non-motile, and rod-shaped bacteria. Three (Y. pestis, Y. enterocolitica, and Y. pseudotuberculosis) of the eleven species in this genus are human pathogens. Y. enterocolitica and Y. pseudotuberculosis are responsible for an estimated 17,000 cases of yersiniosis (hallmarked by enteritis) per year in the U.S. In addition, approximately 20% of patients with ankylosing spondylitis, Reiter’s disease, or reactive arthritis are culture positive for Yersinia species. Cases of Y. pestis, the causative agent of the plague, are more rare with an estimated 13 cases per year in the U.S. Infection with Y. enterocolitica typically occurs in young children. Patients may present with fever, abdominal pain, and acute enteritis. In the assay, we detect IgG and IgA antibodies to Yersinia species in human serum.

Clinical significance: Candida dubliniensis is associated with oral candidiasis and has been recovered from the vaginal tract of women. Although it is closely related to C. albicans, its differences in virulence and its ability to develop resistance to antifungal agents makes it very clinically relevant. The use of molecular techniques, such as Real-Time PCR, enables the clinician to differentiate C. dubliniensis from other species of Candida to facilitate diagnosis and proper treatment.

Clinical significance: C. glabrata accounts for 7% of all vaginal fungal infections and about 15% of vaginal yeast isolates. It has been isolated from patients with septicemia, pyelonephritis, pulmonary infections, and endocarditis. C. glabrata has recently emerged as an important nosocomial infection as well. It is of special importance because of its innately increased resistance to antifungal agents, specifically the azoles. It is thought that the widespread use of topical antifungals, especially in short courses, may contribute to selection for non-albicans yeasts, which are less susceptible to these agents than C. albicans. C. glabrata is of particular concern to immuncompromised individuals. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Candida kefyr is one of the six strains of Candida, of approximately 154 species, that is commonly associated with infections of humans. This species, previously reported in the literature by the obsolete name of Candida pseudotropicalis, has been reported as an emerging pathogen. Candidiasis has a wide clinical spectrum, capable of affecting almost any organ or system in the body. Infections range from localized, superficial infections to dissemination in the blood stream. Considered to be a relatively rare infection, found in approximately 1% of fungal isolates, reported infections include burn wounds, blood and vaginal infections. More recently, the frequency of C. kefyr infections has increased within oncohematologic patients, particularly those with neutropenic, myeloid and lymphoblastoid leukemias.

Clinical significance: Candida krusei has recently emerged as an important nosocomial infection. It is of special importance because of its innately increased resistance to antifungal agents, specifically fluconazole. It is thought that the widespread use of antifungals, especially in short courses, may contribute to selection for non-albicans yeasts, which are less susceptible to these agents than C. albicans. C. krusei is of particular concern to immuncompromised individuals. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Pneumocystis carinii is an opportunistic pathogen which can cause a fatal pneumonia in patients under immunosuppressed or immune deficient conditions due to AIDS, cancer, chemotherapy, or immunosuppressive therapy for organ transplantation. Traditionally, the clinical samples for diagnosis of P. carinii infection by microscopic analysis are mostly from samples of open lung biopsy and bronchoscopic alveolar lavage. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: B. henselae is the causative agent of cat scratch disease (CSD) as well as other conditions. It is commonly seen in immunocomprimised patients, particularly those suffering from HIV infection. The classic clinical presentation of CSD is a self-limiting regional lymphadenopathy, usually caused by a cat scratch or bite. The disease starts with a lesion at the site of infection, which may become a papule. Transmission of the disease has been linked to cats and is also suspected to occur via fleas and ticks. Recently, Bartonella has been detected in immunocompromised patients as well as in Ixodes scapularis ticks, the same ticks that transmit Lyme disease. Evidence is mounting that Bartonella species are also transmitted from ticks to humans and can contribute to the disease manifestations of Lyme disease. Patient serum is analyzed by ELISA for the presence of Bartonella henselae-specific IgG and IgM antibodies.

Clinical significance: Ehrlichia is the causative agent of Ehrlichiosis. This obligate intracellular bacteria is transmitted by the Ixodes tick, the same vector implicated in Lyme disease and Babesiosis. Human Ehrlichiosis was described in the United States for the first time in 1986. Unusual inclusions are noted in patient’s mononuclear cells and were later recognized as being characteristic of the genus Ehrlichia. Human Ehrlichiosis has a fatality rate approaching 5% if treatment with the appropriate antibiotic is not administered in a timely fashion. Two types of human Ehrlichiosis have been recognized, depending on the type of infected blood cells. Human monocytotropic Ehrlichiosis (HME) is caused by infection of mononuclear cells and Human Granulocytic Ehrlichiosis (HGE) is caused by infection of granulocytes. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Serum required

Clinical significance: This assay utilizes a synthetic peptide (C6 peptide) which is derived from the VisE protein of B. burgdorferi. This peptide has been shown to be both specific and highly immunogenic. The peptide sequence is conserved and equally antigenic in humans infected with Borrelia burgdorferi or with European genospecies including B. afzelii and B. garinii. As the antigen represents a defined sequence within the protein, potential cross-reactivity in individuals with unrelated and partially related antigens found in other organisms is greatly reduced. Likewise, cross-reactivity in individuals vaccinated with licensed recombinant OspA Lyme disease vaccine (Lymerix) is not observed.

Serum required

Clinical significance: This assay tests for the qualitative detection of total (IgG and IgM) antibodies to Borrelia burgdorferi in human serum. Detection of antibodies allows diagnosis of an infection when other methods, such as culture or antigen detection, are impractical or yield negative results. This test is the first of a two-step system to provide supportive evidence of exposure to B. burgdorferi, which could support a clinical diagnosis of Lyme disease. This assay should not be used as a sole criterion for diagnosis.

Serum required

Clinical Significance: Chlamydophila pneumoniae seropositivity rates are very low in children under 5 years of age. By the time most people reach early adulthood, 50% are seropositive with rates reaching approximately 75% in the elderly. C. pneumoniae specific IgM antibodies appear approximately 3 weeks after onset of illness; whereas, C. pneumoniae specific IgG antibodies begin to appear about 6-8 weeks after onset. Detection of antibodies allows diagnosis of an infection when other methods, such as culture or antigen detection, are impractical or yield negative results.

Clinical significance: There are three subtypes associated with causing disease in humans. C. pneumoniae causes pneumonia, sinusitis, bronchitis, pharyngitis and has been associated with adult onset asthma, atherosclerotic cardiovascular disease, arthritis, and chronic fatigue syndrome. C. trachomatis is a sexually transmitted disease that also causes conjunctivitis, pneumonia, proctitis, and lymphogranuloma venerium. It is also the cause of ocular trachoma, the leading cause of preventable blindness. Sensitive screening methods are necessary for early detection of Chlamydia infections. Rapid treatment could control and decrease the spread of the disease. MDL has developed a rapid and sensitive PCR-based method for the simultaneous detection and differentiation of Chlamydia sub species from specimens. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Cytomegalovirus (CMV), a member of the herpesvirus family, infects 50-85% of adults in the United States prior to age 40. CMV is also found throughout the world and is transmitted by person-to-person contact through infected body fluids such as saliva, blood, breast milk, and urine. The virus can also be vertically transmitted from mother to child. In most infected individuals, the virus remains dormant and does not cause any significant health issues. However, infection of pregnant women, individuals who work with infants and small children, and immunocompromised patients can be more serious. When symptoms do arise, they usually consist of a mononucleosis-like syndrome along with prolonged fever and hepatitis. In this assay DNA is extracted from the patient specimen and subjected to PCR amplification.

Serum required

Clinical significance: Antibody to viral capsid antigen (VCA) is the most valuable of the EBV specific antibody tests. IgM-VCA appears early in infection and typically disappears within 4-6 weeks. IgG-VCA appears in late acute phase, peaks at 2 to 4 weeks after onset of infection, and may persist throughout a patient’s lifetime. The presence of VCA-IgM antibody with the absence of antibody to EBNA after at least 4 weeks of infection is suggestive of primary infection. Past infection (4-6 months earlier) is usually determined by the presence of both VCA antibodies and EBNA antibodies. Differentiation of the VCA IgG and IgM antibodies is also useful for confirmation when the Monospot test is negative. Susceptibility to EBV infection is also determined by the absence of antibodies to viral capsid antigens.

Clinical significance: EBV is the causative agent of infectious mononucleosis, which occurs, primarily in late adolescence and early adulthood. It is characterized by malaise, fever, hepatosplenomegally, lymphadenopathy, and abdominal discomfort. EBV has also been associated with post-transplant lymphoma, Burkitt’s lymphoma, and nasopharyngeal carcinoma. Reactivations of this disease are suspected in chronic fatigue syndrome. EBV is one of the most common human viruses. It is estimated that worldwide up to as many as 80% to 90% of all adults have at one time been infected. Although it is normally a self-limiting infection, complications can occur such as splenomegaly, hepatitis, pericarditis, or central nervous system involvement. In certain rare instances it may be fatal. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Serum required

Clinical significance: HSV-1 classically presents as herpes gingivostomatitis, an infection of the oral mucosa. It can also cause conjunctivitis, keratitis, and herpetic whitlow. Almost all recurrent cold sores or fever blisters are due to HSV-1. However, genital herpes also can be caused by HSV-1. HSV has been isolated from virtually all visceral or mucocutaneous sites. HSV infections can affect the central nervous system causing aseptic meningitis, HSV encephalitis, and autonomic radiculopathy. Visceral HSV infections include esophagitis, pneumonitis, and disseminated infection. Definitive diagnosis of herpes infections is fundamental to the management of patients and the development of strategies to prevent transmission to partners and neonates. Detection of antibodies allows diagnosis of an infection when other methods, such as culture or antigen detection, are impractical or yield negative results.

Serum required

Clinical significance: The most painful and annoying recurrent genital herpes is due to HSV-2. It can also cause conjunctivitis, keratitis, herpetic whitlow, and herpes gingivostomatitis, an infection of the oral mucosa. HSV has been isolated from virtually all visceral or mucocutaneous sites. HSV infections can affect the central nervous system causing aseptic meningitis, HSV encephalitis, and autonomic radiculopathy. Visceral HSV infections include esophagitis, pneumonitis, and disseminated infection. Definitive diagnosis of herpes infections is fundamental to the management of patients and the development of strategies to prevent transmission to partners and neonates. Detection of antibodies allows diagnosis of an infection when other methods, such as culture or antigen detection, are impractical or yield negative results.

Clinical significance: HSV infection is epidemic in the United States. Genital herpes is the most common cause of genital ulcer disease in the developed world. HSV-1 classically presents as herpes gingivostomatitis, an infection of the oral mucosa. It can also cause conjunctivitis, keratitis, and herpetic whitlow. HSV-2 is the most common cause of genital ulcers in the United States. More than 95% of recurrent disease is due to HSV-2. The main application for HSV subtyping is with regard to the clinical issue of recurrent infection. Most painful and annoying recurrent genital herpes is due to HSV-2, and almost all recurrent cold sores or fever blisters are due to HSV-1. However, genital herpes also can be caused by HSV-1. This type of genital herpes is much less frequently recurrent and each recurrence usually lasts only a few days. It has been documented that as much as one third of herpes infections are due to HSV-1, particularly in adolescents and young adults.

Antigen detection systems for HSV are specific and sensitive when applied to the evaluation of genital lesions, but the titer of HSV present during asymptomatic reactivation is 10- to 100-fold less than the titer present during symptomatic episodes. Therefore, methods based on the detection of viral proteins are not likely to be as sensitive as DNA amplification assays. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Serum required

Clinical significance: Human Herpes Virus 6 is a member of the Herpesviridae family. HHV-6 isolates are classified into two variants, A and B. Although the two variants are very closely related, they have distinct differences in immunologic, biologic, epidemiologic, and molecular properties. Studies indicate that HHV-6 infects nearly all humans by 2 years of age. Although very valuable, serological studies do not differentiate between variants A and B.

Clinical significance: Human Herpes Virus 6 (HHV-6) is a member of the Herpesviridae family. HHV-6 isolates are classified into two variants, A and B. Although the two variants are very closely related, they have distinct differences in immunologic, biologic, epidemiologic, and molecular properties. HHV-6 variant B is the causative agent of the common childhood illness Roseola. HHV-6 variant B has also been associated with Multiple Sclerosis (MS) and other neurological disorders. Variant A is implicated in patients suffering from mononucleosis and HIV. A subset of individuals with chronic fatigue syndrome exhibit HHV-6 variant A infection. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Mycoplasmas are small (0.2 – 0.3 nm), membrane-bound organisms capable of independent self-replication. The most prevalent strains recoverable from the genital tract are Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium. Infants can become colonized with genital mycoplasmas during birth. M. hominis has been linked to pyelonephritis, pelvic inflammatory disease (PID), spontaneous abortion, and postpartum septicemia and fever. Genital mycoplasma infections are usually diagnosed by culture. However, it can take 2 to 5 days to culture M. hominis. In this assay, DNA is extracted from the specimen and subjected to PCR amplification

Clinical significance: Mycoplasma species are the smallest and genetically simplest self-replicating bacteria. Mycoplasma species are ubiquitous in nature and are widely distributed throughout the animal kingdom. They have recently been associated with certain acute and chronic illnesses. They can function as causative agents, cofactors, and opportunistic infections. M. penetrans has been isolated from the urogenital tract and from HIV patients. It is a potential cofactor in AIDS progression. Mycoplasmas have been associated with respiratory illness, urogenital disease, immunosuppressive disease such as HIV infection, cardiac diseases, arthritic syndromes, tick-borne illness, and chronic fatigue syndrome. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.