In-utero infection with HIV-1 associated with suppressed lymphoproliferative responses at birth.

In-utero exposure to HIV-1 may affect the immune system of the developing child and may induce HIV-1-specific immune responses, even in the absence of HIV-1 infection. We evaluated lymphoproliferative capacity at birth among 40 HIV-1-uninfected infants born to HIV-1-infected mothers and 10 infants who had acquired HIV-1 in utero. Cord blood mononuclear cells were assayed using [(3) H]-thymidine incorporation for proliferation in response to HIV-1 p55-gag and the control stimuli phytohaemagglutinin (PHA), Staphylococcus enterotoxin B (SEB) and allogeneic cells. In response to HIV-1 p55-gag, eight (20%) HIV-1-exposed, uninfected (EU) infants had a stimulation index (SI) ≥ 2 and three (30%) in-utero HIV-1 infected infants had SI ≥2. The frequency and magnitude of responses to HIV-1 p55-gag were low overall, and did not differ statistically between groups. However, proliferative responses to control stimuli were significantly higher in EU infants than in infants infected in utero, with a median SI in response to PHA of 123 [interquartile range (IQR) 77-231] versus 18 (IQR 4-86) between EU and infected infants, respectively (P < 0·001). Among infected infants, gestational maturity was associated with the strength of HIV-1 p55-gag response (P < 0·001); neither maternal nor infant HIV-1 viral load was associated. In summary, EU and HIV-1-infected infants mounted HIV-1-specific lymphoproliferative responses at similar rates (20-30%), and although global immune function was preserved among EU infants, neonatal immune responses were significantly compromised by HIV-1 infection. Such early lymphoproliferative compromise may, in part, explain rapid progression to AIDS and death among HIV-1-infected infants.

A highly sensitive rapid diagnostic test for Chagas disease that utilizes a recombinant Trypanosoma cruzi antigen.

Improved diagnostic tests for Chagas disease are urgently needed. A new lateral flow rapid test for Chagas disease is under development at PATH, in collaboration with Laboratorio Lemos of Argentina, which utilizes a recombinant antigen for detection of antibodies to Trypanosoma cruzi. To evaluate the performance of this test, 375 earlier characterized serum specimens from a region where Chagas is endemic were tested using a reference test (the Ortho T. cruzi ELISA, Johnson & Johnson), a commercially available rapid test (Chagas STAT-PAK, Chembio), and the PATH-Lemos rapid test. Compared to the composite reference tests, the PATH-Lemos rapid test demonstrated an optimal sensitivity of 99.5% and specificity of 96.8%, while the Chagas STAT-PAK demonstrated a sensitivity of 95.3% and specificity of 99.5%. These results indicate that the PATH-Lemos rapid test shows promise as an improved and reliable tool for screening and diagnosis of Chagas disease.

Pro-apoptotic effects of tau mutations in chromosome 17 frontotemporal dementia and parkinsonism.

It was recently discovered that mutations of tau cause hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Here we report that cultured SH-SY5Y human neuroblastoma cells transfected with mutated tau genes are more vulnerable to apoptotic stimulus. Two kinds of mutations of tau causing FTDP-17 were examined in the present study: one was in exon 10 (N279K) and the other was in exon 12 (V337M). SH-SY5Y cells transfected with either mutated tau were more vulnerable to serum withdrawal, whereas cells transfected with the wild-type tau or vector alone showed no significant change in apoptotic vulnerability. The increase in the intracellular calcium concentration by the serum withdrawal was significantly greater in the SH-SY5Y cells transfected with mutated tau genes than in cells transfected with the wild-type tau or vector alone. These results suggest that mutations of tau might cause FTDP-17 by these pro-apoptotic functions by disrupting the intracellular calcium homeostasis.