Allyson M. Haislip

Lassa Fever in Post-Conflict Sierra Leone

Background Lassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is a major public health threat in West Africa. When the violent civil conflict in Sierra Leone (1991 to 2002) ended, an international consortium assisted in restoration of the LF program at Kenema Government Hospital (KGH) in an area with the worlds highest incidence of the disease. Methodology/Principal Findings Clinical and laboratory records of patients presenting to the KGH Lassa Ward in the post-conflict period were organized electronically. Recombinant antigen-based LF immunoassays were used to assess LASV antigenemia and LASV-specific antibodies in patients who met criteria for suspected LF. KGH has been reestablished as a center for LF treatment and research, with over 500 suspected cases now presenting yearly. Higher case fatality rates (CFRs) in LF patients were observed compared to studies conducted prior to the civil conflict. Different criteria for defining LF stages and differences in sensitivity of assays likely account for these differences. The highest incidence of LF in Sierra Leone was observed during the dry season. LF cases were observed in ten of Sierra Leones thirteen districts, with numerous cases from outside the traditional endemic zone. Deaths in patients presenting with LASV antigenemia were skewed towards individuals less than 29 years of age. Women self-reporting as pregnant were significantly overrepresented among LASV antigenemic patients. The CFR of ribavirin-treated patients presenting early in acute infection was lower than in untreated subjects. Conclusions/Significance Lassa fever remains a major public health threat in Sierra Leone. Outreach activities should expand because LF may be more widespread in Sierra Leone than previously recognized. Enhanced case finding to ensure rapid diagnosis and treatment is imperative to reduce mortality. Even with ribavirin treatment, there was a high rate of fatalities underscoring the need to develop more effective and/or supplemental treatments for LF.

Use of antipolymer antibody assay in recipients of silicone breast implants

BACKGROUND Local complications (encapsulation, rashes, rupture, and leakage) can occur after placement of silicone gel-containing breast implants (SBI). Whether SBI exposure results in systemic manifestations in some recipients is controversial. We have carried out a blinded study to assess whether there is any difference between SBI recipients and non-exposed controls in the proportions positive for serum antibodies directed against polymeric substances. METHODS We recruited female SBI recipients (including those without symptoms) who presented to a single rheumatology clinic. A physician global assessment was used to classify SBI recipients who did not meet criteria for specific autoimmune diseases according to the severity of local and systemic signs and symptoms. Controls were recruited from among clinic staff and their acquaintances. Results of the antipolymer antibody (APA) assay were compared with those of an assay for antinuclear antibodies (ANA) and with the severity of the signs and symptoms. FINDINGS Positive APA results were found in one (3%) of 34 SBI recipients with limited symptoms, two (8%) of 26 with mild symptoms, seven (44%) of 16 with moderate symptoms, and 13 (68%) of 19 with advanced symptoms. Four (17%) of 23 healthy non-SBI-exposed controls and two (10%) of 20 non-exposed women with classic autoimmune diseases were positive for APA. Thus, women with moderate or advanced symptoms were significantly more likely than those with limited or mild symptoms, or non-exposed controls to have APA (p < 0.001). The proportion with positive ANA results was higher for women with classic autoimmune diseases 14 (70%) of 20 than for any SBI-exposed subgroup (0-33%). INTERPRETATION The APA assay can objectively contribute to distinguishing between SBI recipients with limited or mild signs and symptoms. SBI recipients with more severe manifestations, and patients with specific autoimmune diseases. Further studies will be needed to define the signs and symptoms associated with exposure to SBI.

Alterations in intracellular potassium concentration by HIV-1 and SIV Nef.

BackgroundHIV-1 mediated perturbation of the plasma membrane can produce an alteration in the transmembrane gradients of cations and other small molecules leading to cell death. Several HIV-1 proteins have been shown to perturb membrane permeability and ion transport. Xenopus laevis oocytes have few functional endogenous ion channels, and have proven useful as a system to examine direct effects of exogenously added proteins on ion transport.ResultsHIV-1 Nef induces alterations in the intracellular potassium concentration in CD4+ T-lymphoblastoid cells, but not intracellular pH. Two electrode voltage-clamp recording was used to determine that Nef did not form ion channel-like pores in Xenopus oocytes.ConclusionThese results suggest that HIV-1 Nef regulates intracellular ion concentrations indirectly, and may interact with membrane proteins such as ion channels to modify their electrical properties.

Down-regulation of cell surface CXCR4 by HIV-1.

BackgroundCXC chemokine receptor 4 (CXCR4), a member of the G-protein-coupled chemokine receptor family, can serve as a co-receptor along with CD4 for entry into the cell of T-cell tropic X4 human immunodeficiency virus type 1 (HIV-1) strains. Productive infection of T-lymphoblastoid cells by X4 HIV-1 markedly reduces cell-surface expression of CD4, but whether or not the co-receptor CXCR4 is down-regulated has not been conclusively determined.ResultsInfection of human T-lymphoblastoid cell line RH9 with HIV-1 resulted in down-regulation of cell surface CXCR4 expression. Down-regulation of surface CXCR4 correlated temporally with the increase in HIV-1 protein expression. CXCR4 was concentrated in intracellular compartments in H9 cells after HIV-1 infection. Immunofluorescence microscopy studies showed that CXCR4 and HIV-1 glycoproteins were co-localized in HIV infected cells. Inducible expression of HIV-1 envelope glycoproteins also resulted in down-regulation of CXCR4 from the cell surface.ConclusionThese results indicated that cell surface CXCR4 was reduced in HIV-1 infected cells, whereas expression of another membrane antigen, CD3, was unaffected. CXCR4 down-regulation may be due to intracellular sequestering of HIV glycoprotein/CXCR4 complexes.