LABORATORY NETWORK FOR HIV INFECTION IN ETHIOPIA

ABSTRACT: One of the main objectives of the Short Tern Plan of the Ethiopian AIDS Control Programme was the establishment of screening laboratories in blood banks in the country and strengthening the Immunology Laboratory of the National Research Institute of Health. As a result, HIV screening laboratories were established in all five blood banks and the National Referral Laboratory for AIDS (NRLA) was established during the first half of the short tenn plan. Based on the Medium Term Plan of the programme which envisaged establishment of HIV screening laboratories in all regional hospitals where a substantial amount of blood transfusion took place, HIV screening laboratories were established. To date there are 24 HIV screening laboratories throughout the country .Nineteen of these laboratories use ELISA tests and 5 use simple/rapid assays. There is a well established quality control and supervision system where each laboratory is visited twice a year and characterized panels of sera are sent to each laboratory three times a year from the NRLA. The plan of the National AIDS Control Programme is to establish screening laboratories in all establishments where blood transfusion is carried out

In vitro demonstration of intestinal absorption mechanisms of different sugars using 3d organotypic tissues in a fluidic device

Intestinal permeability is crucial in regulating the bioavailability and, consequently, the biological effects of drugs and compounds. However, systematic and quantitative studies of the absorption of molecules are quite limited due to a lack of reliable experimental models able to mimic human in vivo responses. In this work, we present an in vitro perfused model of the small intestinal barrier using a 3D reconstructed intestinal epithelium integrated into a fluid-dynamic bioreactor (MIVO\uae) resembling the physiological stimuli of the intestinal environment. This platform was investigated in both healthy and induced pathological conditions by monitoring the absorption of two non-metabolized sugars, lactulose and mannitol, frequently used as indicators of intestinal barrier dysfunctions. In healthy conditions, an in vivo-like plateau of the percentage of absorbed sugars was reached, where mannitol absorption was much greater than lactulose absorption. Moreover, a model of pathologically altered intestinal permeability was generated by depleting extracellular Ca2+ using a calcium-specific chelator. After calcium depletion, the pattern of sugar passage observed under pathological conditions was reversed only in dynamic conditions in the MIVO\uae chamber, due to the dynamic fluid flow beneath the membrane, but not in static conditions. Therefore, the combination of the MIVO\uae with the EpiIntestinal\u2122 platform can represent a reliable in vitro model to study the passage of molecules across the healthy or pathological small intestinal barrier by discriminating the two main mechanisms of intestinal absorption

ELISA FALSE POSITIVITY IN RELATION TO HIV -1 PREVALENCE IN ETHIOPIA

ABSTRACT: A close investigation of data accumulated over several years at the National Referral Laboratory for AIDS (NRLA), revealed a certain pattern in the number of false positive results that occur in population groups with a given prevalence of HIV -1 infection. To provide more accurate information regarding this observation 8850 serum samples from females with multi-partner sexual contact (MPSC) residing in different regions of Ethiopia with varying HIV -1 prevalence rates, were collected and tested using 1st and 2nd generation enzyme immunoassays (EIA) and a western blot. The results obtained from this study suggest that the rate of the occurrence of false positive enzyme linked imrnuno-sorbent assay (ELISA) results during laboratory testing for HIV -1 antibody is (regardless of the quality of antigen used) inversely proportional to the prevalence of HIV-l in a given population group

HIV-1 INFECTION AMONG EMPLOYEES OF THE ETHIOPIAN FREIGHT TRANSPORT CORPORATION

SUMMARY: In the study on HIV-l infection conducted in July 1988, 995 long distance truck drivers, their assistants, and lorry technicians employed by the Ethiopian Freight Transport Corporation (EFTC) were enrolled. 89.4% of trips made by the drivers were along the Addis Ababa -Assab road. The HIV prevalence rates were 13% among 468 drivers, 12.9% among 209 drivers assistants, and 4.1% among 318 technicians. The prevalence rate among those who served for < 5 yrs was 4.7% (n = 297) .Those who served longer in the Corporation (82.9% of whom are drivers) had a mean prevalence rate of 12.5% (n=698). Drivers had more sexual partners and more frequently experienced sexually transmitted diseases than the technicians. The study indicated that the long distance truck drivers in Ethiopia practiced frequent contacts with female sex workers. They were at a significantly higher risk to acquire HIV infection than the technicians employed at the same corporation

Interaction of Dendritic Cells with Skin Endothelium: A New Perspective on Immunosurveillance

The goal of this study was to determine the mechanisms by which dendritic cells (DCs) in blood could interact with endothelium, a prerequisite to extravasation into tissues. Our results indicate that DCs express both HECA-452–reactive and nonreactive isoforms of P-selectin glycoprotein ligand 1 (PSGL-1) and can tether and roll efficiently on E- and P-selectin under flow conditions in vitro. Freshly isolated blood DCs were further observed to roll continuously along noninflamed murine dermal endothelium in vivo. This interaction is strictly dependent on endothelial selectins, as shown by experiments with blocking antibodies and with E- and P-selectin–deficient mice. We hypothesize that DCs in blood are constitutively poised at the interface of blood and skin, ready to extravasate upon induction of inflammation, and we showed that cutaneous inflammation results in a rapid recruitment of DCs from the blood to tissues. We propose that this is an important and previously unappreciated element of immunosurveillance

Chip-based human liver-intestine and liver-skin co-culture : A first step toward systemic repeated dose substance testing in vitro

Systemic repeated dose safety assessment and systemic efficacy evaluation of substances are currently carried out on laboratory animals and in humans due to the lack of predictive alternatives. Relevant international regulations, such as OECD and ICH guidelines, demand long-term testing and oral, dermal, inhalation, and systemic exposure routes for such evaluations. So-called “human-on-a-chip” concepts are aiming to replace respective animals and humans in substance evaluation with miniaturized functional human organisms. The major technical hurdle toward success in this field is the life-like combination of human barrier organ models, such as intestine, lung or skin, with parenchymal organ equivalents, such as liver, at the smallest biologically acceptable scale. Here, we report on a reproducible homeostatic long-term co-culture of human liver equivalents with either a reconstructed human intestinal barrier model or a human skin biopsy applying a microphysiological system. We used a multi-organ chip (MOC) platform, which provides pulsatile fluid flow within physiological ranges at low media-to-tissue ratios. The MOC supports submerse cultivation of an intact intestinal barrier model and an air–liquid interface for the skin model during their co-culture with the liver equivalents respectively at 1/100.000 the scale of their human counterparts in vivo. To increase the degree of organismal emulation, microfluidic channels of the liver–skin co-culture could be successfully covered with human endothelial cells, thus mimicking human vasculature, for the first time. Finally, exposure routes emulating oral and systemic administration in humans have been qualified by applying a repeated dose administration of a model substance – troglitazone – to the chip-based co-cultures.BMBF/0315569/GO-Bio 3: Multi-Organ-Bioreaktoren für die prädiktive Substanztestung im Chipforma

HIV-1 INFECTION AND RELATED RISK FACTORS AMONG FEMALE SEX WORKERS IN URBAN AREAS OF ETHIOPIA

SUMMARY: A total of 6234 female sex workers practicing multi-partner sexual contacts (MPSC) from 23 urban areas of the country were tested for Human Immuno deficiency Virus type 1 (HIV1) infection, in 1988. The sample size ranged from 99 persons in Moyale, to 386 in Asmara. The mean age of the individuals studied was 24.2 years (ranging from 21.5 years to 27.1 years in the different towns). The HIV-1 prevalence rates varied from 1.3% (n=318) in Massawa, to 38.1% (n=312) in Dessie town; the mean for all towns being 17%. The highest prevalence rates were found in the towns along the road from Addis Ababa to Assab, in Bahr-Dar , Dessie and Mekele. The lowest prevalence rates were recorded in three towns of northern Ethiopia. This study indicated that Hiv-1 is widely spread in the urban areas of Ethiopia affecting female sex workers mainly in the 15-29 years age group. Previous episodes of other sexually transmitted diseases, and frequent change of sexual partners were identified as possible risk factors for HIV infection. Frequent mobility of these females may have played a significant role in HIV transmission between the towns

HIV -1 INFECTION AND SOME RELATED RISK FACTORS AMONG FEMALE SEX WORKERS IN ADDIS ABABA

SUMMARY: A sero-epidemiological survey on HIV-l infection was carried out in July 1989, among four groups of female sex workers randomly selected in Addis Ababa. The four groups were comprised of: bar girls, tej (traditional wine) sellers, tella (traditional beer) sellers and females in red light houses. Sera were tested by ELISA and confirmed y western blot. The mean age of the 2617 females studied was 31.2 years, and the prevalence rate for HIV-1 was 24.7%. Persons in the 15-24 age group were affected more frequently. The highest prevalence (43.8%) was found among the females in red light houses. Females with relatively larger number of sexual partners and those who had previous exposure to STDs, had a higher prevalence of the infection. The survey revealed that HIV-1 is highly prevalent among females practicing multi-partner sexual contact (MPSC) in Addis Ababa, and the infection concentrates in the central areas of the city

Chemokine receptor CCR2 is expressed by human multiple myeloma cells and mediates migration to bone marrow stromal cell-produced monocyte chemotactic proteins MCP-1, -2 and -3

The restricted bone marrow (BM) localisation of multiple myeloma (MM) cells most likely results from a specific homing influenced by chemotactic factors, combined with the proper signals for growth and survival provided by the BM microenvironment. In analogy to the migration and homing of normal lymphocytes, one can hypothesise that the BM homing of MM cells is mediated by a multistep process, involving the concerted action of adhesion molecules and chemokines. In this study, we report that primary MM cells and myeloma derived cell lines (Karpas, LP-1 and MM5.1) express the chemokine receptor CCR2. In addition, we found that the monocyte chemotactic proteins (MCPs) MCP-1, -2 and -3, three chemokines acting as prominent ligands for CCR2, are produced by stromal cells, cultured from normal and MM BM samples. Conditioned medium (CM) from BM stromal cells, as well as MCP-1, -2 and -3, act as chemoattractants for human MM cells. Moreover, a blocking antibody against CCR2, as well as a combination of neutralizing antibodies against MCP-1, -2 and -3, significantly reduced the migration of human MM cells to BM stromal cell CM. The results obtained in this study indicate the involvement of CCR2 and the MCPs in the BM homing of human MM cells. (C) 2003 Cancer Research UK

C. albicans Colonization of Human Mucosal Surfaces

Background: Candida albicans is a low level commensal organism in normal human populations with the continuous potential to expand and cause a spectrum of clinical conditions. Methodology/Principal Findings: Using ex vivo human organ cultures and populations of primary human cells, we have developed several related experimental systems to examine early-stage interactions between C. albicans and mucosal surfaces. Experiments have been conducted both with exogenously added C. albicans and with overtly normal human mucosal surfaces supporting pre-existing infections with natural isolates of Candida. Under different culture conditions, we have demonstrated the formation of C. albicans colonies on human target cells and filament formation, equivalent to tissue invasion. Conclusions/Significance: These organ culture systems provide a valuable new resource to examine the molecular and cellular basis for Candida colonization of human mucosal surfaces