The role of IgG avidity determination in diagnosis of Epstein-Barr virus infection in immunocompetent and immunocompromised patients

There is a high degree of variability in the serologic response to Epstein-Barr virus (EBV) infection, especially in viral capsid antigen (VCA)-IgM antibodies. Therefore, additional tests are needed to confirm primary infection. We evaluated the value of IgG avidity determination in diagnosis of EBV infection in immunocompetent and immunocompromised patients. A total of 236 serum samples from immunocompetent patients with symptoms suggestive of EBV infection were tested for the presence of VCA-IgM/IgG antibodies and IgG avidity. Using IgG avidity, acute primary infection was confirmed in 56.7% of the immunocompetent patients with positive and in 1.8% of patients with negative VCA-IgM. Recent primary infection was documented in 8.9% of the IgM positive and 3.5% of the IgM negative patients. In patients with indeterminate serology (equivocal IgM), 6.7% were classified by avidity index (AI) as acute primary infection, 10.0% as post-acute and 83.3% as past infection cases. Concerning the 32 immunocompromised patients, recent primary infection was documented in 3 of the 14 IgM positive patients. High AI was detected in 11 of these patients, indicating an IgM response due to reactivation. Determination of IgG avidity in combination with classical serologic markers seems to be a reliable method to confirm primary infection both in immunocompetent and immunocompromised patients. It may be especially useful to differentiate cases of primary infection in patients with undetectable VCA-IgM antibodies or indeterminate routine EBV serology.     

The role of IgG avidity in diagnosis of cytomegalovirus infection in newborns and infants

To evaluate the value of IgG avidity in diagnosis of congenital cytomegalovirus (CMV) infection in newborns and infants we collected serum samples from 40 infants under 12 months of age with suspected congenital CMV infection. Sera were tested for IgM, IgG and IgG avidity. For 25 of them, virus isolation and/or polymerase chain reaction (PCR) on urine specimens were performed. Thirteen (32.5%) patients showed the presence of CMV IgM antibodies, 3 (7.5%) had equivocal IgM result, and 24 (60.0%) patients had IgG antibodies only. Using IgG avidity, CMV infection (low avidity index-AI) was documented in 61.5% IgM positive and 54.2% IgM negative patients. Eight of nine (88.8%) IgM positive patients were positive either on virus isolation or PCR. In IgM negative patients, 46.6% urine cultures were positive for CMV and 66.6% were PCR positive. According to age, IgG avidity demonstrated acute/recent primary CMV infection in 58.8% patients younger than three months compared with 91.7% and 81.8% in 3-6 and 6-12 months old babies, respectively. In conclusion, IgG avidity is useful in diagnosis of CMV infection either in IgM positive or IgM negative children older than 3 months of age. In infants less than 3 months, transplacentally derived maternal IgG antibodies of high avidity influence on the IgG avidity result. In these children, CMV infection should be confirmed by direct virologic methods such as virus isolation or PCR.     

Subacute sclerosing panencephalitis--the continuing threat

Clinical, epidemiological and laboratory findings of four patients with subacute sclerosing panencephalitis (SSPE), diagnosed in Croatia in 2002, were examined. Patient age at disease onset ranged from 5-11 years. All patients were vaccinated regularly with MMR-vaccine. Two patients had a history of measles infection at the age of six and seven months, respectively. In the other two patients, the disease started immediately after the varicella infection. Complement fixing antibody titre to the measles virus (MV) ranged from 1:1024 to 1:65536 in serum, and from 1:16 to 1:128 in cerebrospinal fluid (CSF). In CSF, no antibodies to varicella-zoster virus were found. Brain tissue samples were obtained at autopsy from two patients. In one patient, electron microscopy demonstrated intranuclear viral inclusions (MV nucleocapsids). MV antigen was detected in brain imprints using IFA in both of them. Viral RNA was found in brain tissue samples only, while plasma, serum and CSF were negative. Nucleotide sequence analysis showed that the viruses detected in brain tissue belong to the wild-type MV D6 genotype.     

Seroprevalence of Taenia solium infections in Croatian patients presenting with epilepsy

Epilepsy is one of the most common neurological disorders, while neurocysticercosis caused by Taenia solium infection of the central nervous system currently represents the leading cause of secondary epilepsy in Central and South America, East and South Asia, and sub-Saharan Africa. As a result of increased migration from these endemic regions, neurocysticercosis and subsequent epilepsy are becoming a growing public health problem in developed countries as well. In order to determine the prevalence of T. solium infection in patients with epilepsy in Croatia, a retrospective serological study was conducted. A total of 770 serum samples were tested for the presence of T. solium IgG antibodies using a commercial qualitative enzyme immunoassay. The Western blot technique was used as a confirmatory test for the diagnosis. The overall seroprevalence rate of T. solium infection in patients with clinically proven epilepsy was 1.5%. Although the results have shown that infection with this tapeworm is rare in Croatia, this study hopes to increase awareness about the importance of preventive measures and benefits of accurate and timely diagnosis. Intervention measures for infection control are crucial, namely sanitation improvement, control of domestic pig-breeding, detailed meat inspection, detection and treatment of tapeworm carriers, hand washing and health education.     

Subacute sclerosing panencephalitis in Croatia (1994-2004)

We studied five patients with SSPE during a 10-year period (1994-2004). The first clinical symptoms developed at the age of 5-11 years. All patients were vaccinated regularly against measles according to the official immunization schedule. One patient had measles at the age of 18 months. Two of them had a history of morbilliform rash (unrecognized measles) at the age of six and seven months, respectively. In two patients, with no history of measles before vaccination the disease started after varicella infection. Using complement-fixation (F) test and EIA, antibodies to measles virus (MV) were detected in the CSF and sera of all patients. The CF-antibody titers ranged from 1:1024 to 1:65536 in sera and from 1:16 to 1:128 in CSF samples. MV antigen was detected in brain imprints using IFA in two patients. Electron microscopic analysis revealed intranuclear viral inclusions (MV nucleocapsids). Using RT-PCR, viral RNA was found in both patients. Nucleotide sequence analysis showed that the viruses found in the brain tissue belonged to the wild-type MV D6 genotype [7].