Adeno-associated virus and development of cervical neoplasia

Evidence from several sources has suggested that adeno-associated virus (AAV) infection might protect against cervical cancer, in part, by interfering with human papillomavirus (HPV)-induced tumorigenesis. Detection of AAV type 2 (AAV-2) DNA in cervical tissues has been reported. However, there have been few in vivo studies of women with cervical HPV infection or neoplasia, and these have reported inconsistent results. Therefore, we used polymerase chain reaction (PCR) assays targeted to the AAV-2 rep and cap genes to test tissue specimens from women in an epidemiological study of cervical neoplasia in Jamaica. We tested 105 women with low-grade cervical intraepithelial neoplasia (CIN-1), 92 women with CIN-3/carcinoma in situ or invasive cancer (CIN-3/CA), and 94 normal subjects. PCR amplification of human beta-globin DNA was found in almost all cervical specimens, indicating that these materials were adequate for PCR testing. The prevalence of HPV DNA, determined by HPV L1 consensus primer PCR was, as expected, strongly associated with presence and grade of neoplasia. Each of the AAV PCR assays detected as few as 10 copies of the virus genome. However, none of the 291 cervical specimens from Jamaican subjects tested positive for AAV DNA. Negative AAV PCR results were also obtained in tests of cervical samples from 79 university students in the United States. Exposure to AAV was assessed further by serology. Using a whole virus AAV-2 sandwich enzyme-linked immunosorbent assay, we found no relationship between AAV antibodies and presence or grade of neoplasia in either the Jamaican study subjects or women enrolled in a U.S. cervical cancer case (n = 74) - control (n = 77) study. Overall, the data provide no evidence that AAV infection plays a role in cervical tumorigenesis or that AAV commonly infects cervical epithelial cells.(Au)

Nephrotic syndrome and human parvovirus infection in homozygous sickle-cell disease: a temporal association - abstract

Proteinuria of sufficient severity to manifest the nephrotic syndrome and renal impairment has been associated with human parvovirus (B19) infection in 7 patients with homozygous sickle-cell (SS) disease. In most patients, the proteinuria resolved but renal impairment remained. The glomerular histology showed evidence of segmental proliferative glomerulonephritis in 4 out of 5 biopsies. Most events occurred within 2 weeks of B19 associated aplastic crisis, and the mechanism is at present unknown. This association may add to the pathogenic significance of B19 infection in SS disease (AU)

Management of sickle cell disease; lessons from the Jamaican Cohort Study

Sickle cell disease is enormously variable in its expression and outcome. In addition to this intrinsic variablity are the problems of symptomatic selection biasing observations towards the sever end of a wide clinical spectrum and a truly changing natural history as a result of better management. Against this background, there was a need for a description of the disease in a truly representative sample of patients and this objective has been approached in the Jamaican Cohort Study of Sickle Cell Disease. Initiated in 1973, this study is based on all cases of sickle cell disease detected among 100,000 consecutive normal deliveries in Kingston, Jamaica. All affected children as well as age matched normal controls have been followed prospectively and are currently ages 11 to 19 years. The following review is based on lessons learnt from this cohort study. It is not intended to be a comprehensive survey of knowledge of sickle cell disease and does not address major contributions from studies elsewhere. In some ways, therefore, the review may appear unbalanced because of this specific objective. However, a great deal has been learnt about the evolution of the abnormal haematology of sickle cell disease and its relationship to clinical features. The causes of early mortality in sickle cell disease in Jamaica are described and the major complications such as acute splenic sequestration, pneumococcal septicaemia, aplastic crisis, hypersplenism, and acute chest syndrome have been addressed with varying success. Overall survival to the age of 19 years has been 75 percent and it is planned that the study should continue to define the problems of late adolescence and early adult life (AU)

Parvovirus infection and the aplastic crisis of sickle cell disease - abstract

The aplastic crisis is a temporary self-limited erythropietic maturation arrest which, because of the short red cell survival in homozygous sickle-cell (SS) disease, results in rapid fall in haemoglobin level. These aplastic crises occur in epidemics, predominantly affect children, frequently involve siblings simultaneously, and often follow an upper respiratory tract type of infection. Recent evidence suggests that these events may follow human parvovirus (HPV) infection and the role of HPV infection has been examined in the last three epidemics of aplastic crises observed among SS patients in Jamaica. Eighteen patients were affected in the 1973-1975 epidemics, 45 in the 1979-1981 epidemic, and 41 so far in an epidemic in 1984-1985. Serological studies have been possible in 73 patients and in 69 (95 percent) there was evidence consistent with recent HPV infections. This infection appears to confer long-lasting immunity, and recurrent attacks of aplastic crisis have never been described. These data suggest that a parvovirus vaccine may be beneficial in the prevention of aplastic crises (AU)