Herpes simplex virus type 2 infections of the central nervous system: A retrospective study of 49 patients.

Herpes simplex virus type 2 (HSV-2) infections of the central nervous system (CNS) are rare with meningitis as the most common clinical presentation. We have investigated the clinical spectrum of CNS infections in 49 adult consecutive patients with HSV-2 genome in the cerebrospinal fluid (CSF). HSV-2 in the CSF was determined by polymerase chain reaction (PCR), and patients were diagnosed as encephalitis or meningitis according to predefined clinical criteria by retrospective data information from consecutive clinical journals. The annual crude incidence rate of HSV-2 CNS disease was 0.26 per 100,000. 43 (88%) had meningitis of whom 8 (19%) had recurring lymphocytic meningitis. Six patients (12%) had encephalitis. 11 of 49 patients (22%) had sequelae recorded during follow-up. None died as a result of HSV-2 CNS disease. Thus, the clinical presentation of HSV-2 infection of the CNS is mainly meningitis but encephalitis does occur and neurological sequelae are common. Recurring lymphocytic meningitis is associated with reactivation of HSV-2 and the condition might be underdiagnosed.

Varicella zoster in Guinea-Bissau: intensity of exposure and severity of infection.

OBJECTIVE: To describe the epidemiology of and risk factors for severe chickenpox in Guinea- Bissau. METHODS: A prospective household study in a semiurban area of the capital. Severity was assessed by number of pox, fever response and presence of pneumonia. Severity was compared for the first case in a house, that is, the index case, and the secondary cases infected at home. RESULT: We identified 1539 cases of chickenpox. The median age was lower for boys and secondary cases (both P < 0.03); 44.6% of children were 1-4 years of age. The likely minimum interval between index and secondary cases was 10 days; most secondary cases occurred 14-17 days after the index case. The length of the incubation period was related to the intensity of exposure (P < 0.01). The number of pox was higher for secondary cases (P < 0.01) and was related to intensity of exposure (P < 0.01). Secondary cases had higher fever and more frequently pneumonia (relative risk, 2.17; 95% confidence interval, 1.54-3.08). Children with pneumonia were younger and had more pox. Nutritional status was not related to severity. CONCLUSIONS: Age and intensity of exposure are important determinants for severity of chickenpox infection. The length of the incubation period depends on intensity of exposure, suggesting that the dose of infection might be important.

T-lymphocyte subsets and eosinophil counts in acute and convalescence chickenpox infection: a household study in Guinea-Bissau.

OBJECTIVE: To investigate changes in T-lymphocyte subsets, CD4+ and CD8+ lymphocytes, WBC, lymphocytes and eosinophil granulocytes during the acute and the convalescence phase of chickenpox infection. METHODS: During an epidemic of chickenpox, a household study was performed in a semi-urban area of Bissau, Guinea-Bissau. Varicella antibodies were determined to assess diagnostic certainty. To determine the timing of changes, haematological markers and T-cell subsets (immunocytochemical method) were analysed in the acute phase, 0-9 days after the rash, and in the convalescence phase, 35-45 days after the rash. RESULTS: In the acute phase, the CD4 percentage, CD4/CD8 ratio, and neutrophil percentage declined, whereas the CD8 percentage, WBC, CD4 and CD8 counts, and the lymphocyte percentage increased over the same period, most markedly for the CD8 count. The eosinophil percentage increased significantly with time from onset of rash. Between acute and convalescence samples there was an increase in CD4 percentage, CD4/CD8 ratio, and CD4 count, and a marked decrease in CD8 percentage and CD8 count. The changes were not significant for WBC, lymphocyte percentage, neutrophil percentage, and monocyte percentage, but eosinophil percentage was significantly increased 5-7 weeks after the onset of rash. The haematological changes were related to number of pox and intensity of exposure; a high eosinophil percentage was associated with less severe disease, i.e. less pox. CONCLUSION: We report significant changes in T-lymphocyte subsets during the acute phase of chickenpox infection, including a suppression of CD4+ T-cells and an augmentation of CD8+ T-cells. The levels were normalized 1 month later except for eosinophils, and we found no persistent CD4 suppression after chickenpox. An increased number of eosinophils in the peripheral blood was demonstrated early in the acute phase of the disease, and remained elevated in the convalescence phase.

An international external quality assessment of nucleic acid amplification of herpes simplex virus.

BACKGROUND: There is an increasing awareness of the need for external quality control of diagnostic virology. OBJECTIVES: To assess the quality of nucleic acid amplification tests (NAT) of herpes simplex within Europe. STUDY DESIGN: Herpes simplex virus (HSV) proficiency panels were produced at the Swedish Institute for Infectious Disease Control on behalf of the European Union Concerted Action for Quality Control of Nucleic Acid Amplification in 1999 and 2000. Nine reference laboratories evaluated the production process. Each panel consisted of 12 coded samples with various concentrations of inactivated, freeze-dried HSV type 1 (HSV-1), and HSV type 2 (HSV-2), or negative controls. Positive samples included HSV-1 and HSV-2 in a range of concentrations (2 x 10(2) to 2 x 10(7) genome copies per ml) similar to those found in cerebrospinal fluids from patients with HSV encephalitis. RESULTS: Sixty-six participants reported a total of 76 data sets for panel 1, and 71 reported 78 data sets for panel 2. The majority of the participants employed qualitative 'in-house' polymerase chain reaction (PCR) methods, either in a single, nested or semi-nested format. For panel 2, 9 laboratories reported use of 'real-time' PCR in contrast to 3 for panel 1. Three laboratories submitted quantitative results on both panels. Thirty percent of the data sets had correct results for the entire panel 1. In 6 data sets (8%) a total of 11 false positive results were reported. For panel 2, 28% of the data sets had correct result. Nineteen false positive results were reported in 14 data sets (18%), but most of the incorrect results reflected a lack of test sensitivity. CONCLUSIONS: The relatively high frequency of false positive results and the large number of false-negative results, albeit at low copy number, stress the need for improvement in the quality of HSV NAT and for external quality control programmes.

A mu-capture immunoassay for detection of human herpes virus-6 (HHV-6) IgM antibodies in human serum.

BACKGROUND: Human herpes virus-6 (HHV-6) was first isolated in 1986. It has been shown to cause exanthema subitum and has been associated with various other diseases. HHV-6 infection is widespread, and more than 90% of the population have antibodies against HHV-6 at the age of 2 years. Once acquired, the virus remains latent in the body. This makes it difficult to draw any conclusions about a causal relationship between the demonstration of HHV-6 and a specific disease. OBJECTIVES: This work was to develop a mu-capture HHV-6 IgM enzyme linked immuno sorbent assay (ELISA) for use in routine diagnosis and for wide scale patient population analysis. STUDY DESIGN: A mu-capture HHV-6 IgM ELISA was established. A total of 682 sera consisting of 585 sera from Danish blood donors and 97 sera from patients with autoimmune antibodies were analysed in the HHV-6 IGM ELISA. One hundred and ninety-two sera had earlier been analysed for total HHV-6 antibody content in a competitive ELISA, 94 sera were analysed for cytomegalovirus (CMV) IgM and 57 sera for Epstein Barr virus (EBV) antibodies, using different ELISA assays. The results for 12 primary infections with HHV-6 are also reported. RESULTS: A HHV-6 IgM optical density (OD)-ratio was calculated according to a constant positive control. An empirical cut off of 0.5 HHV-6 IgM OD-ratio was chosen (with regard to the 10 HHV-6 seroconverters), which resulted in a specificity of 97.5% of the HHV-6 IgM ELISA. Two of the three donor sera with HHV-6 IgM OD-ratios more than 1.05 had total HHV-6 antibody titers significantly above the group with IgM OD-ratios below 0.7 consisting with HHV-6 reactivation. There was no cross reactions to EBV or CMV IgM positive sera. CONCLUSION: The HHV-6 IgM ELISA seems valid to diagnose primary HHV-6 infection in particular in combination with the HHV-6 total antibody assay.