Clinical Review

New screening tests: HSV, CMV, HBV, HCV, parvovirus, and HIV

OBG Manag. 2005 October;17(10):46-53

Tips on choosing the right tests and getting valid results

References

1. Heyman B. Regulation of antibody responses via antibodies, complement and Fc receptors. Annu Rev Immunol. 2000;18:709-737.

2. Ashley RL. Sorting out the new HSV type specific antibody tests. Sex Transm Infect. 2001;77:232-237.

3. Bodeus M, Van Ranst M, Bernard P, Hubinont C, Goubau P. Anticytomegalovirus IgG avidity in pregnancy: a 2-year prospective study. Fetal Diagn Ther. 2002;17:362-366.

4. Ashley-Morrow R, Krantz E, Wald A. Time course of seroconversion by HerpeSelect ELISA after acquisition of genital herpes simplex virus type 1 (HSV-1) or HSV-2. Sex Transm Dis. 2003;30:310-314.

5. Wald A, Huang ML, Carrell D, Selke S, Corey L. Polymerase chain reaction for detection of herpes simplex virus (HSV) DNA on mucosal surfaces: comparison with HSV isolation in cell culture. J Infect Dis. 2003;188:1345-1351.

6. Eggers M, Metzger C, Enders G. Differentiation between acute primary and recurrent human cytomegalovirus infection in pregnancy, using a microneutralization assay. J Med Virol. 1998;56:351-358.

7. Maine GT, Lazzarotto T, Landini MP. New developments in the diagnosis of maternal and congenital CMV infection. Expert Rev Mol Diagn. 2001;1:19-29.

8. Bodeus M, Hubinont C, Bernard P, Bouckaert A, Thomas K, Goubau P. Prenatal diagnosis of human cytomegalovirus by culture and polymerase chain reaction: 98 pregnancies leading to congenital infection. Prenat Diagn. 1999;19:314-317.

9. Dinsmoor MJ. Hepatitis in the obstetric patient. Infect Dis Clin North Am. 1997;11:77-91.

10. Duff P. Hepatitis in pregnancy. Semin Perinatol. 1998;22:277-283.

11. Pawlotsky JM. Use and interpretation of virological tests for hepatitis C. Hepatology. 2002;36(suppl 1):S65-S73.

12. Dienstag JL. Sexual and perinatal transmission of hepatitis C. Hepatology. 1997;26(suppl 1):S66-S70.

13. Jordan JA. Diagnosing human parvovirus B19 infection: guidelines for test selection. Mol Diagn. 2001;6:307-312.

14. Brown KE. Parvovirus B19. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 6th ed. Philadelphia: Elsevier; 2005.

15. Katta R. Parvovirus B19: a review. Dermatol Clin. 2002;20:333-342.

16. Beelaert G, Vercauteren G, Fransen K, et al. Comparative evaluation of eight commercial enzyme linked immunosorbent assays and 14 simple assays for detection of antibodies to HIV. J Virol Methods. 2002;105:197-206.

17. Schramm W, Angulo GB, Torres PC, Burgess-Cassler A. A simple saliva-based test for detecting antibodies to human immunodeficiency virus. Clin Diagn Lab Immunol. 1999;6:577-580.

18. Makuwa M, Souquiere S, Niangui MT, et al. Reliability of rapid diagnostic tests for HIV variant infection. J Virol Methods. 2002;103:183-190.

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Fast Track

Erroneous assumption: IgM is found only in acute infection and disappears within 3 months

Viral cultures for herpes simplex have very low sensitivity; only positive results are clinically useful

A woman is a hepatitis B carrier if the virus’ surface antigen persists 6 months after primary infection

A positive hepatitis C antibody test must be confirmed by nucleic amplification or recombinant immunoblot assay

Screen all women for HIV who are sexually active, diagnosed with another STD, or pregnant

It can take up to 1 year for a patient to seroconvert after acute HIV infection

IN THIS ARTICLE

Signs of a hepatitis B carrier
Sensitivity and specificity of viral screening tests
Who should be screened for HIV?

Technology makes many things possible, but not without imposing new responsibilities. When it comes to viral infections, diagnosis through serology testing, antigen assays, or amplification techniques such as polymerase chain reaction (PCR) now is possible for a number of diseases, including:

herpes simplex virus (HSV),
cytomegalovirus (CMV),
hepatitis B and C viruses (HBV, HCV),
parvovirus B19 (B19), and
human immunodeficiency virus (HIV).

The responsibilities that come along with this ability: keeping up to date and selecting the most sensitive and specific test possible. This article reviews the latest tests and offers advice on their use in detecting 6 viruses.

How to pick the right test

When a patient’s presentation suggests viral infection, when something in her history raises a red flag, or when she reports possible exposure to a virus, the right test is critical to the diagnosis. The right test also helps prevent false positives and avoid confusion—but which test is best?

Which immunoglobulins matter?

Many of us have been taught that immunoglobulin M (IgM) correlates with acute infection, but that is not necessarily the case. Because of its high molecular weight, IgM is found most commonly in the intravascular compartment and is not transported to the fetus. IgM usually becomes apparent early during the course of infection. It has a half-life of 10 days and usually—but not always—regresses to undetectable levels over a few months.

The misconception that IgM is found only in acute infection and disappears within 3 months causes many clinicians to test for it and to misinterpret the results. In many cases, IgM fails to develop after acute infection. In others, it may persist for as long as 2 years after primary infection. It also can be detected with recurrent or reactivated infections.¹

Immunoglobulin G (IgG) has a longer half-life (21 days) and is the most common immunoglobulin in humans. It is found in tissues and serum and readily crosses the placenta. It can be detected shortly after acute infection, exhibiting a steep rise and fall over several weeks after primary infection. IgG also is a sign of past infection.¹

Telltale sign of acute infection

It now seems clear that an IgG antibody produced within the first months after primary infection binds to its antigen poorly. After this initial period, the IgG binds with greater intensity (ie, higher avidity) to that specific antigen (virus). Assays that measure this binding intensity are called avidity assays and are expressed as a percentage of IgG bound to the antigen after treatment with denaturing agents.

Avidity assays have been developed and studied for a variety of viruses.² The detection of low-avidity IgG can be considered a more reliable sign of acute infection than IgM.

Herpes simplex virus

SERENA’S CASE

Monthly irritation and a vulvar lesion

Serena, 22, complains of irritation and pruritus that precede her period each month. She has tried treating herself with over-the-counter and prescription antifungal medication, without much relief. She presents to your office as an add-on patient and reports that the irritation started 1 day ago and usually lasts 7 days. Physical examination reveals a small area on the left vulva that is inflamed, with 2 small fissures. You obtain a vaginal pH, but it is normal, and there are negative findings on the wet prep.

In view of Serena’s history of recurrent symptoms and atypical lesions, recurrent herpes is a likely diagnosis, so you culture the lesion and order IgG type-specific serology for HSV 1 and 2. The culture is negative, but serology is positive for the HSV-2 antibody. Thus, serology confirms genital herpes.

Although Serena’s culture was negative, false-negative cultures are common with HSV, and serology testing usually is necessary to make the diagnosis of recurrent genital herpes.

HSV-2 is widespread: About 1 in 4 adults is infected. Of these, fewer than 1 in 10 is aware he or she has the virus. Thus, it makes sense to test for HSV-2 when physical findings suggest that it may be present.