Laboratory Diagnosis and Characteristics of Breakthrough Varicella in Children

Abstract

The atypical features of varicella in vaccinated persons (breakthrough varicella [BTV]) present diagnostic challenges. We examined varicella-zoster virus (VZV) polymerase chain reaction (PCR) and immunoglobulin (Ig) M and IgG serologic test results for confirming BTV cases. Among 33 vaccinated children with varicella-like rash, we identified wild-type VZV in 58% overall and in 76% of those with adequate tissue specimens; no vaccine-type virus was found. Of the 12 subjects with PCR-confirmed BTV and acute-phase serum samples, 9 had detectable IgM, and all had highly elevated acute-phase IgG titers. Six subjects with negative PCR results had lower IgG titers and negative IgM results. Although PCR is the preferred method for laboratory confirmation of BTV, a positive serum varicella IgM test result should also be considered to be diagnostic in a suspected BTV case; however, a negative IgM test result cannot be used to rule out the diagnosis. The value of highly elevated IgG titers needs further evaluation. Larger studies are needed to confirm these results.

Ege Üniversitesi Tıp Fakültesi Hastanesine başvuran hastalarda Varisella Zoster Virüs serolojik test sonuçlarının değerlendirilmesi

“…Çalışmamızda, yaş-ları 1 ile 95 arasında değişen (ortalama değer 23.05 yaş) hasta grubunda Varisella IgG olumlu- VZV enfeksiyonu mikrobiyolojik tanısında farklı laboratuvar yöntemleri kullanılmaktadır. Hastalığın erken döneminde veziküllerin PCR ile test edilmesinin tanıda duyarlı ve özgül olduğu gösterilmiştir (11,12) . Yine oral sürüntü örnekle-rinin de PCR ile test edilmesi oldukça duyarlı bir yöntem olarak bildirilmektedir (13) .…”

Microbiology laboratory and the management of mother-child varicella-zoster virus infection

“…The gpELISAs are ELISAs that use the external glycoproteins (typically gE, gB, gH) as antigens of the solid phase [219,339,371,[404][405][406][407][408][409][410][411][412] . They are sensitive enough to detect low antibody levels after vaccination, and have been used to evaluate the level of protection [407] : In one study, 95% of the vaccinated subjects had a gpELISA value of ≥ 5 U/ mL six weeks after immunisation, whereas those with values of < 5 were at three times greater risk of developing BV [413] .…”

“…IgM and IgA antibodies have been used as indicators of recent or current infection, but they may also be present during re-infections and reactivations [30,64,153,410] . In general, neither direct or capture IgM tests are as sensitive as molecular biology tests [5,30,410,443,446] , and they may also be non-specific in the presence of high IgG titres [5,30,348] .…”

“…IgM and IgA antibodies have been used as indicators of recent or current infection, but they may also be present during re-infections and reactivations [30,64,153,410] . In general, neither direct or capture IgM tests are as sensitive as molecular biology tests [5,30,410,443,446] , and they may also be non-specific in the presence of high IgG titres [5,30,348] . It is probable that the time of sampling may be important because Leung et al [474] found that only 25% of their PCR-positive patients with varicella showed IgM in samples taken 0-3 d after the onset of the rash, whereas other authors found that the percentage rose to 48% after four days [85] or 77% after 1-7 d [410] .…”

“…However, it may be of help when assessing seroconversion or a 4-fold increase in titre between acute and convalescent serum samples taken 7-10 d apart, although the need for two samples postpones the diagnosis [74,408,410] . Furthermore, people with a history of varicella or vaccination may have higher levels of basic IgG, and a 4-fold increase may therefore not be noticeable in the case of re-infection or BV [30] , especially in the elderly [30,474] , and IgG may sometimes no longer be present after two weeks of rash, thus lengthening seroconversion times [481] .…”