Screening for neurocognitive impairment in HIV-positive adults aged 50 years and older: Montreal Cognitive Assessment relates to self-reported and clinician-rated everyday functioning.

As the HIV+ population ages, the risk for and need to screen for HIV-associated neurocognitive disorders (HAND) increases. The aim of this study is to determine the utility and ecological validity of the Montreal Cognitive Assessment (MoCA) among older HIV+ adults. A total of 100 HIV+ older adults aged 50 years or over completed a comprehensive neuromedical and neurocognitive battery, including the MoCA and several everyday functioning measures. The receiver operating characteristic curve indicates ≤26 as the optimal cut-off balancing sensitivity (84.2%) and specificity (55.8%) compared to "gold standard" impairment as measured on a comprehensive neuropsychological battery. Higher MoCA total scores are significantly (p < .01) associated with better performance in all individual cognitive domains except motor abilities, with the strongest association with executive functions (r = -0.49, p < .01). Higher MoCA total scores are also significantly (p <.01) associated with fewer instrumental activities of daily living declines (r = -0.28), fewer everyday cognitive symptoms (r = -0.25), and better clinician-rated functional status (i.e., Karnofsky scores; r = 0.28); these associations remain when controlling for depressive symptoms. HIV+ individuals who are neurocognitively normal demonstrate medium-to-large effect size differences in their MoCA performance compared to those with asymptomatic neurocognitive impairment (d = 0.85) or syndromic HAND (mild neurocognitive disorder or HIV-associated dementia; d = 0.78), while the latter two categories do not differ. Although limited by less than optimal specificity, the MoCA demonstrates good sensitivity and ecological validity, which lends support to its psychometric integrity as a brief cognitive screening tool among older HIV+ adults.

Mutant p53 protein in serum could be used as a molecular marker in human breast cancer.

p53 wild-type is a tumor suppressor gene involved in DNA gene transcription or DNA repair mechanisms. When damage to DNA is unrepairable, p53 induces programmed cell death (apoptosis). The mutant p53 gene is the most frequent molecular alteration in human cancer, including breast cancer. Here, we analyzed the genetic alterations in p53 oncogene expression in 55 patients with breast cancer at different stages and in 8 normal women. We measured by ELISA assay the serum levels of p53 mutant protein and p53 antibodies. Immunohistochemistry and RT-PCR using specific p53 primers as well as mutation detection by DNA sequencing were also evaluated in breast tumor tissue. Serological p53 antibody analysis detected 0/8 (0%), 0/4 (0%) and 9/55 (16.36%) positive cases in normal women, in patients with benign breast disease and in breast carcinoma, respectively. We found positive p53 mutant in the sera of 0/8 (0.0%) normal women, 0/4 (0%) with benign breast disease and 29/55 (52.72%) with breast carcinoma. Immunohistochemistry evaluation was positive in 29/55 (52.73%) with mammary carcinoma and 0/4 (0%) with benign breast disease. A very good correlation between p53 mutant protein detected in serum and p53 accumulation by immunohistochemistry (83.3% positive in both assays) was found in this study. These data suggest that detection of mutated p53 could be a useful serological marker for diagnostic purposes.

Serum antibodies in canine echinococcosis.

Specific IgG, IgA and IgE antibodies against E. granulosus protoscolex antigen were detected by enzyme-linked immunosorbent assay (ELISA) in sera from dogs experimentally or naturally infected with E. granulosus. The specificities of the IgG, IgA and IgE ELISAs were 100, 100 and 97.3%, respectively. Sera from 626 dogs of different categories and geographic regions in Australia, Uruguay and Kenya were tested. There were distinct differences in antibody responses in experimentally infected canids and in the number of naturally infected dogs found seropositive, depending on geographic region. The overall sensitivities of the ELISA (IgG, IgA and IgE) ranged between 73 and 84%, except for one geographic region where it was 54%. Genetic differences of the dogs and/or antigenic variations of the parasite appear to be responsible for the variations in specific antibody levels in infected dogs. In average, approximately one third of dogs from hyperendemic hydatid regions, without E. granulosus worms at autopsy or negative for E. granulosus infection by arecoline testing, were seropositive for anti-E. granulosus antibodies, suggesting previous infection with or exposure to the parasite. The results of this study demonstrate that, although the diagnosis of current intestinal E. granulosus infection on an individual dog basis is not always reliable by serology, serum antibody ELISA is useful as an epidemiological/educational tool for seroprevalence studies on canine echinococcosis.

Human cystic echinococcosis in a Uruguayan community: a sonographic, serologic, and epidemiologic study.

A prevalence and transmission study of human cystic echinococcosis (CE), due to infection with the dog tapeworm Echinococcus granulosus, was undertaken in the village of La Paloma in central Uruguay. The human population was registered and screened for CE by abdominal ultrasound scan as well as a number of serologic tests. Dogs were screened for E. granulosus infection by arecoline purgation as well as specific coproantigen testing. The total prevalence of human CE (new cases and those with a previous history) was 5.6% (64 of 1,149); 3.6% (40) of the cases were new ultrasound detected asymptomatic cases (mean age = 45 years). Age prevalence increased from 1.1% in the 4-6-year-old group to > 11% in the > 60-year-old group; the 20-29-year-old group had a significantly higher CE rate of 7.4%, compared with younger and older age groups, and there was no difference between sexes. A CE rate of 3.9% (20 of 514) was also recorded by ultrasound for new cases in the population residing outside the village. Most of the hydatid cysts were located in the liver presenting as either univesicular cysts or a solid mass, and of those 71% and 63%, respectively, with such cyst presentations were seropositive against E. granulosus cyst fluid antigens. Two of eight individuals who were filter paper blood spot seropositive, but ultrasound scan negative, were subsequently diagnosed respectively with pulmonary hydatidosis after radiography, and hepatic hydatidosis after computed tomography scan. Of 36 households with a CE patient, 32 were single cases while four households each harbored two CE cases. This did not represent a clustered distribution within families (23 of 117). Almost 20% of the dogs from La Paloma were found infected with E. granulosus after purge examination, with a mean worm number of 67 (range = 1-1,020). An additional eight dogs that were purge negative were Echinococcus coproantigen positive. The study showed that human CE is highly endemic in Uruguay, with one of the highest local prevalence rates in the world. Transmission appears to occur readily within well-developed towns, as well as on rural sheep ranches. Mass screening by ultrasound scanning with confirmatory serologic testing is an effective approach to case detection at the community level.

IgG1 and IgG4 serum antibody responses in asymptomatic and clinically expressed cystic echinococcosis patients.

IgG1 and IgG4 subclass antibody responses were investigated in two clinically different groups of hepatic cystic echinococcosis (CE) patients. One group consisted of surgically proven CE cases (clinically expressed hospitalized cases) and a second group comprised asymptomatic CE patients (first time community detected cases) diagnosed by portable ultrasound and serology in four different endemic communities. Fifty eight sera from surgically proven CE patients and 133 sera from asymptomatic ultrasound diagnosed CE cases were screened by ELISA using purified human hydatid cyst fluid antigen B for total specific IgG, IgG1 and IgG4 antibodies. Fifty sera from healthy individuals from within endemic regions were used as control negatives. Compared to control negatives total IgG antibody levels were elevated in both surgically proven (85%) and asymptomatic CE cases (77%) but there was no significant difference between the two groups. IgG1 subclass antibody levels were also elevated in both surgically proven (55%) and asymptomatic cases (58%) compared to endemic controls and similarly the difference in this response was not significant between these two groups. In contrast the prevalence of IgG4 antibodies in surgically confirmed chronic CE patients was greater (71%) than the respective IgG1 antibody levels (55%). The greatest difference in specific antibody response, between advanced surgically confirmed CE patients and ultrasound detected asymptomatic CE cases, was observed for IgG4 antibody levels which were detected in 71% of symptomatic compared to only 23% of asymptomatic patients (P < 0.0001). These observations confirm that IgG4 is an important diagnostic parameter for clinically expressed cystic echinococcosis in humans and suggest that a switch from a predominant IgG1 response to IgG4 might occur in CE patients as the disease progresses.

Immunological assessment of exposure to Echinococcus granulosus in a rural dog population in Uruguay.

An ELISA was used to screen a dog population in Uruguay (Sarandi Del Yi, Durazno District) for the prevalence of specific serum antibodies (IgG, IgA and IgE) to Echinococcus granulosus. The sensitivity (61%) and specificity (97%) of the ELISA were determined using well-defined serum groups. A total of 408 dogs from Sarandi del Yi and environs were screened serologically, and 29.7% (8.6-13.8% for each antibody class) of dogs had positive levels of antibody to E. granulosus. This antibody prevalence (exposure) was significantly higher than the percentage of dogs found to be positive for E. granulosus worms by arecoline purgation (7.6%). This level of exposure to E. granulosus determined by ELISA is considered unacceptable from a public health perspective. Measures will now focus on obtaining data on the true prevalence of current infection in this dog population and on determining the transmission patterns of the disease in this endemic region.

Diagnosis of canine echinococcosis: comparison of coproantigen and serum antibody tests with arecoline purgation in Uruguay.

Echinococcus granulosus is one of the most important and widespread of the helminth zoonoses. Diagnosis of E. granulosus infection in dogs currently relies on arecoline dosing and detailed examination of the purge for adult worms. Two immunodiagnostic tests (ELISA) based on genus specific coproantigen detection or serum antibody (IgG, IgA and IgE) detection were compared against arecoline purgation for the detection of Echinococcus in naturally infected dogs in Uruguay. The coproantigen ELISA had a sensitivity of 76.9% compared with 34.6% for the serum IgG ELISA when assessed against 26 purge positive dogs (purge worm count range 1-4331). Coproantigen reactivity was positively correlated (r = 0.65) to purge worm count, with a threshold at over 20 worms. There was no positive correlation of antibody levels with worm counts. In 26 matched Echinococcus positive dog samples, the overall sensitivity of serological detection increased to 69.2% when seroreactivity for IgA and IgE antibodies were included and to 96.2% for both coproantigen and antibody assays combined. The detection of current infection of individual dogs with E. granulosus by coproantigen ELISA has the potential to replace arecoline purgation, while specific serum antibody detection should be useful in assessing Echinococcus exposure in dog populations.

Echinococcus granulosus infections of dogs in the Durazno region of Uruguay.

The prevalence and distribution of Echinococcus granulosus in domestic dogs was examined in three dog populations in the Durazno region of Uruguay. The prevalence was 19.7 per cent in 704 dogs successfully purged with arecoline hydrobromide. Higher prevalences were detected in dogs from the rural area (30.0 per cent) and the village of La Paloma (25.9 per cent) than in the town of Sarandi del Yi (7.9 per cent). The frequency distribution of E granulosus was overdispersed (k, the negative binomial parameter = 0.08), with only a few animals harbouring heavy infections. The results of a questionnaire showed that the prevalence was greatest in male dogs, in dogs that were not kennelled, in dogs that had access to fields and in dogs that were not dosed with praziquantel. Dogs that were given raw sheep offal by their owners were no more likely to be parasitised than other dogs; this may reflect the inaccuracy of the owners' replies, or that the dogs were being infected outside their home.