Roberto Novati

A comparision of brain biopsy and CSF-PCR in the diagnosis of CNS lesions in AIDS patients

Abstract Twenty patients with AIDS who had intracranial lesions underwent both brain biopsy and cerebro-spinal fluid (CSF) examination to compare histological diagnosis with the polymerase chain reaction (CSF-PCR) for the identification of infectious agents. CSF-PCR was performed for herpes simplex virus, varicella zoster virus, cytomegalovirus (CMV), JC virus (JCV), Epstein-Barr virus (EBV), Toxoplasma gondii and Mycobacterium tuberculosis. A definitive diagnosis was obtained by brain biopsy in 14 patients (2 with astrocytoma, 12 with brain infection). CSF-PCR was positive for EBV DNA in 3 of 3 cases of primary cerebral lymphoma, positive for JCV DNA in 6 of 7 biopsy-proven (and one autopsy-proven) cases of progressive multifocal leukoencephalopathy (PML). CSF-PCR was positive for CMV DNA in one biopsy-proven and one autopsy-proven case of CMV encephalitis (the former also had PML) and positive for M. tuberculosis DNA in one case of tuberculous encephalitis. None of the five toxoplasmic encephalitis cases (one definite, four presumptive) were T. gondii DNA positive. There was close correlation between histology and CSF-PCR for CMV encephalitis, PML and PCL. Antitoxoplasma therapy affected the sensitivity of both histological and CSF-PCR methods.

Detection of hepatitis C virus genomic sequences in the cerebrospinal fluid of HIV‐infected patients

To assess the presence of hepatitis C virus (HCV) in the central nervous system (CNS), HCV‐RNA was sought in paired serum and cerebrospinal fluid (CSF) samples of 21 HIV/HCV‐positive patients: HCV‐RNA was detected in the serum of 19/21 patients (90.4%), and in the CSF of five of the 19 serum‐positive patients. The presence of HCV‐RNA was confirmed in follow‐up CSF samples available for three of these five patients. An identical HCV genotype was found in the paired serum/CSF samples. No correlation was found between the different genotypes and the presence of HCV in CSF of the individual patients.

Access to antiretroviral treatment, incidence of sustained therapy interruptions, and risk of clinical events according to sex: Evidence from the I.Co.N.A. study

Objectives of the study were to assess the differences between sexes in the likelihood of starting antiretroviral therapy (ART), in rates of sustained discontinuation from highly active antiretroviral therapy (HAART), and in clinical progression. In a multicenter cohort study (I.Co.N.A. Study), 2323 men and 1335 women previously naive to antiretrovirals were enrolled. As of September 2002, 807 women and 1480 men started ART. The median time to starting ART was 28 weeks for women and 17 weeks for men (P = 0.0003 by log-rank test). This difference was no longer significant after adjusting for either HIV RNA (P = 0.21) or CD4 count (P = 0.28) at enrollment. Women tend to start HAART less frequently than mono/dual ART after adjusting for potential confounders (odds ratio = 0.78, 95% confidence interval [CI]: 0.60-1.01; P = 0.06). Women who started HAART were 1.4 times more likely than men (95% CI: 1.00-1.99; P = 0.05) to interrupt at least 1 drug because of toxicity. Twenty-one percent of women and 19% of men interrupted HAART altogether for more than 3 months (P = 0.3). Clinical progression was observed in 53 women (22.6%) and 137 men (23.4%; P = 0.56). Risk of developing a clinical event was found to be no different between women and men (relative hazard = 0.84, 95% CI: 0.56-1.26; P = 0.40).

Rheumatoid factors and circulating immune complexes in HIV-infected individuals

We studied serological aspects of autoimmunity in patients with AIDS, AIDS-related complex (ARC) and in individuals at risk for AIDS. Immunoglobulin (Ig) M, IgG and IgA rheumatoid factors (RF) were quantified by enzyme-linked immunosorbent assay (ELISA), Ig by radial immunodiffusion, and circulating immune complexes (CIC) by the CIC-conglutinin and CIC-complement 1q (C1q) assays. Mean IgM RF levels were normal in AIDS patients, but those of ARC patients were higher and more frequent than the levels defined by agglutination methods. Similar observations were made for intravenous drug users (IVDU) and for both HIV-seropositive and HIV-seronegative homosexual men. Mean IgG RF levels were normal in AIDS and ARC patients but high in homosexual men and, to a lesser degree, in IVDU. IgA RF levels were high in many AIDS and ARC patients, in homosexual men, and in haemophiliac and control groups. The selective increase of the IgA isotype in AIDS was confirmed by the Ig results, which also showed an IgG increase in all groups. IgM were mainly high in people with ARC. CIC were detected in 68% of ARC patients by both methods, and in 55% of AIDS patients by CIC-Clq. A high incidence of positive samples in all at-risk populations, but particularly in seronegative individuals, was observed using CIC-conglutinin. CIC-C1q also revealed larger amounts of CIC in HIV-seronegative individuals, mainly in homosexual men. The study of these humoral aspects of autoimmunity provides useful information on the impairment of B-cells in patients with AIDS and ARC.(ABSTRACT TRUNCATED AT 250 WORDS)

T-cell subsets and serum immunoglobulin levels in infants born to HIV-seropositive mothers: A longitudinal evaluation

T-lymphocyte subsets and serum immunoglobulins were assayed in 27 neonates and 12 infants younger than 6 months, all born to HIV-seropositive mothers. No differences in T-lymphocyte subsets between the 27 seropositive and 34 seronegative infants were found at birth. Twelve seroreverted and 14 infected children were followed. CD4+ cell counts were significantly lower in the latter at 3 and 24 months of age. Serum immunoglobulin levels and CD8+ percentages became higher in the infected group, starting from the sixth month, while CD4+ percentages and CD4+/CD8+ ratios became lower, starting from the twelfth month.

Neurobrucellosis with spinal cord abscess of the dorsal tract: a case report

Neurologic manifestations of brucellosis occur in 2-5% of patients.l.* The clinical pictures of neurobrucellosis are characteristically protean: they include meningoencephalitis, meningovascular complications, parenchymatous dysfunctions, peripheral neuropathy/radiculopathy and various degrees of behavioral abnormalities, sometimes leading to acute psychosis. From the clinical series available, meningitis has been referred as the most frequent presentation of neurobrucellosis, occurring in at least the 50% of cases;‘,” meningitis is most often acute, but subacute or chronic presentations are not rare and may lead to disseminated encephalomyelitis with diffuse central nervous system (CNS) demyelinization.3*4 In contrast, Bruceh abscess formation within the CNS has been described up to now in just one child with multiple brain abscesses.’ We here report the first case of neurobrucellosis with intramedullary abscess in an adult. A 24-year-old man from Sicily was admitted to the regional Hospital for high degree continuous fever and night sweats; fever had lasted for about two months and had been treated with a one-week course of oral prednisolone, before the patient was admitted to hospital. The patient remembered eating some fresh goat’s cheese in the recent past. Thus, brucellosis was suspected and the Brucella melitensis serum agglutination test (SAT) was performed. This was positive at a 1:SOO titer. A six-week cycle of rifampin 600 mglday and doxycycline 100 mg b.i.d. was given; both the fever and the agglutinins normalized. Six months later he complained of abrupt onset of fever, hypostenia of the left leg, and paresthesias of the right leg, with consequent impaired walking. A contrast-enhanced magnetic resonance imaging (MRI) of the brain and the spinal cord showed a focal lesion of 15 mm diameter within the dorsal tract of the spinal cord, near to the third intervertebral space; the abscess was surrounded by perilesional edema, had a partially liquid core and a ring enhancement was evident after Gadolinium in-

Maternal predictors of HIV vertical transmission

We performed a retrospective study of 57 HIV-positive pregnant women and their children to look for maternal parameters related to rates of vertical transmission of HIV. Sixteen (28%) infants were HIV-infected. There was no positive correlation between maternal risk factors for HIV and vertical transmission of HIV. Multiparity seemed to be related to a higher prevalence of vertical transmission, whereas neither preterm delivery nor cesarean section resulted in different rates of vertical transmission, although they tended to have some protective effect. Maternal beta 2-microglobulin and serum neopterin levels were not related to different rates of vertical transmission of HIV. CD4+ cell counts did so only when cut-off values of 400/mm3 were taken. All the women in CDC group IV and all the HIV p24 antigen-positive transmitted the infection to their infants, whereas only 7/48 women in CDC groups II and III (P = 0.000006) and 9/48 HIV p24 antigen negative women (P = 0.00006) gave birth to infected infants. No other maternal characteristics were associated with different rates of vertical transmission in a multivariate analysis restricted to women in CDC groups II and III and with HIV p24 antigen negativity.

Early diagnosis of HIV infection in infants.

Eighteen infants born to anti-HIV-positive mothers were tested bimonthly for immunoglobulin M (IgM) anti-HIV by Western blot and HIV p24 antigen (Ag) by enzyme-linked immunosorbent assay (ELISA) in order to determine the role of these markers in the early diagnosis of HIV infection. Twelve healthy infants were also studied as a control group. In 11 out of 18 children (61.1%) an IgM response was demonstrable, in 13 out of 18 (72.2%) IgM anti-HIV and/or p24 antigen (Ag) were detected. Two patterns of IgM response were identified: a precocious IgM positivity (group of five children positive at birth) and a later appearance of IgM, always within the third month (six cases). Early p24 antigenemia occurred in one infant. Three out of four children who developed antigenemia after birth were symptomatic within the sixth month. No clinical or immunological abnormalities were found among the three children who were persistently negative for both IgM anti-HIV and p24 Ag. Serial IgM anti-HIV and p24 Ag testing may be helpful in the early identification of HIV-infected patients.

Mother to child transmission of hepatitis C virus detected by nested polymerase chain reaction

Serum samples from eight pregnant women and their offspring were studied by nested polymerase chain reaction (PCR) for detection of hepatitis C virus (HCV) RNA to evaluate mother-to-child transmission of this virus. The mothers were all infected with human immunodeficiency virus (HIV); none showed symptoms of HCV infection. Anti-HCV antibodies were tested for by recombinant immunoblot assay. HCV viral sequences were found in five of the mothers and four of eight children, three of them at birth. Viremia was persistent in one infant who had chronic transaminase elevation and persistently remained anti-HCV-positive. The other three babies had intermittent viremia; all were asymptomatic and lost anti-HCV antibodies during follow-up. This loss of antibodies was also observed in PCR-negative infants. Thus, these results demonstrate transmission of HCV from mother to child by women coinfected with HCV and HIV. They indicate the usefulness of PCR for direct and early detection of HCV viremia in neonates.