Systemic FasL and TRAIL neutralisation reduce leishmaniasis induced skin ulceration.

Cutaneous leishmaniasis (CL) is caused by Leishmania infection of dermal macrophages and is associated with chronic inflammation of the skin. L. aethiopica infection displays two clinical manifestations, firstly ulcerative disease, correlated to a relatively low parasite load in the skin, and secondly non-ulcerative disease in which massive parasite infiltration of the dermis occurs in the absence of ulceration of epidermis. Skin ulceration is linked to a vigorous local inflammatory response within the skin towards infected macrophages. Fas ligand (FasL) and Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expressing cells are present in dermis in ulcerative CL and both death ligands cause apoptosis of keratinocytes in the context of Leishmania infection. In the present report we show a differential expression of FasL and TRAIL in ulcerative and non-ulcerative disease caused by L. aethiopica. In vitro experiments confirmed direct FasL- and TRAIL-induced killing of human keratinocytes in the context of Leishmania-induced inflammatory microenvironment. Systemic neutralisation of FasL and TRAIL reduced ulceration in a model of murine Leishmania infection with no effect on parasitic loads or dissemination. Interestingly, FasL neutralisation reduced neutrophil infiltration into the skin during established infection, suggesting an additional proinflammatory role of FasL in addition to direct keratinocyte killing in the context of parasite-induced skin inflammation. FasL signalling resulting in recruitment of activated neutrophils into dermis may lead to destruction of the basal membrane and thus allow direct FasL mediated killing of exposed keratinocytes in vivo. Based on our results we suggest that therapeutic inhibition of FasL and TRAIL could limit skin pathology during CL.

Assessment of the implementation of HIV-rapid test kits at different levels of health institutions in Ethiopia.

OBJECTIVE: Evaluation and monitoring of Human Immunodeficiency Virus (HIV) testing reagents at the point of service is helpful to prevent the occurrence of problems related to testing and interpretation. To evaluate the implementation of HIV rapid test kits at the point of services in voluntarily counseling and testing (VCT) and diagnostic centers in Ethiopia. METHODS: The assessment was the third phase of evaluation of HIV rapid test kits in Ethiopia followed from phase-I and phase-II. Known proficiency testing panels, well-structured questionnaire (addressing type of tests, human resource and problems related to tests), onsite supervision and retesting of samples collected from sites were used to evaluate the performances of reagents and laboratories. RESULTS: Forty-four health institutions were included. Thirty-six (90.0%) health institutions had trained human resource on HIV testing. In 27 (61.4%) three types of HIV rapid test kits (Determine, Capillus and Unigold) were available. Serial-algorithm was used in all the laboratories. In 31 (70.4%) of them external quality control specimens were not used. Twenty two (50.0%) of the laboratories reported frequent shortage of reagents. All (100%) were able to identify negative specimens distributed. Positive proficiency panel samples were identified in 37 (94.8%) of the 39 laboratories. There was 98.3% agreement at a screening level between the sites and the central laboratory. Rate of discrepancy between screening and confirmatory assays was found to be 3.0% and 2.1% at the sites and at central laboratory, respectively. CONCLUSION: The test kits showed a good performance at the point of services in the field sites. However, continuous assessment of HIV test kits at the point of service and training of professionals on newly arrived techniques are recommended to have effective testing performance with acceptable sensitive and specific testing algorithm. Effective quality assurance program should be in place to support programs such as VCT, prevention of mother-to-child-transmission and antiretroviral therapy.

Prevalence and incidence of, and risk factors for, HIV-1 infection among factory workers in Ethiopia, 1997-2001.

The study was conducted to determine the prevalence, incidence, and risk factors for HIV infection among factory workers at two sites in Ethiopia. During February 1997-December 2001, a structured questionnaire was used for obtaining information on sociodemographics, sexual behaviour, and reported sexually transmitted infections (STIs) from a cohort of 1679 individuals. Serum samples were screened for antibodies against HIV, Treponema pallidum haemaglutination (TPHA), and herpes simplex virus type 2 (HSV-2). The overall baseline prevalence of HIV was 9.4%-8.5% among males and 12.4% among females. For both the sexes, the factors independently associated with an increased risk of HIV infection were widowhood and having had antibodies against TPHA and HSV-2. The risk factors specific for males were being orthodox Christian, having had a higher lifetime number of sexual partners, and genital discharge in the past five years. The risk factors for females, included low income, one or more rape(s) over lifetime, and casual sex in the last year. The overall incidence of HIV infection was 0.4 per 100 person-years. The highest rate of incidence was observed among young women aged less than 30 years (1 per 100 person-years). The study confirmed that high-risk sexual behaviour and STIs play major roles in the spread of HIV infection in the Ethiopians of both the sexes, but the factors, such as rape and low economic status, make women more vulnerable than men.

Nine-year trends in HIV-1 prevalence among visa applicants in Urban Ethiopia.

A retrospective study was conducted to examine trends in HIV-1 prevalence among visa applicants between the years 1993 to 2001 in Urban Ethiopia. A total of 63,869 visa applicants were screened during these nine years period. The majority of them (79.5%) were females. Their mean age was 31.6 and 25.7 years for males and females, respectively. HIV-1 prevalence ranged from 6.8% in 1993 to 10.4% in 1997 (test for trend: p<0.001), while it seems stabilized at around 11% after 1997. The overall period prevalence was 9.5%. The peak prevalence was documented in the age group 25-29 for females (12.1%) while it was in the age group 30-34 for males (11.4%). This study, therefore, confirms the severity of the HIV-1 epidemic in the country. Visa applicants can be used as a sentinel population for monitoring trends in HIV-1 prevalence in the country, although additional socio-demographic information would be useful for better interpretation of such data.

Evaluation of rapid assays for screening and confirming HIV-1 infection in Ethiopia.

To evaluate a simple and rapid testing strategy to diagnose HIV infection in Ethiopia, we subjected a panel of 688 sera with known HIV serologic status (confirmed by ELISA/WB or double ELISA) to 3 rapid assays: Determine HIV-1/2, Capillus HIV-1/2 and Serocard HIV. Samples were obtained from participants in a cohort study on HIV-infection (72%), from tuberculosis patients (18%) and from participants in surveillance studies among police recruits and commercial sex workers (10%). The panel consisted of 249 HIV-1 positive samples, of which 68 were HIV-1 subtype C and 1 HIV-1 subtype A, and 439 HIV-1 negative samples. Determine and Capillus were 100% sensitive and 99.8% specific, Serocard was 100% sensitive and specific. On retrospective evaluation, both parallel (samples tested simultaneously by two rapid assays) and serial (samples tested by two consecutive rapid assays) testing algorithms were 100% sensitive and specific when compared to ELISA/WB or double ELISA testing strategy. In conclusion rapid assays have high sensitivity and specificity. HIV serodiagnosis based on rapid assays may therefore be a valuable alternative in voluntary counselling and testing centres and in facilities where sophisticated laboratories are not available.