Isoniazid prophylaxis for tuberculosis prevention among HIV infected police officers in Dar Es Salaam

Objective: To determine the acceptability, compliance and side effects of isoniazid (INH) prophylaxis against tuberculosis among HIV infected police officers (PO) in Dar es Salaam.Design: A nested study from a prospective follow up of a cohort of police officers.Setting: Dar es Salaam, Tanzania.Subjects: One hundred and forty three HIV-1 infected police officers.Main outcome measures: Acceptance and compliance to INH prophylaxis.Results: Of the 400 HIV-1 infected officers, 143 (35.7%) came forward for post-test counselling and HIV test results. Sixty per cent (87/143) of them accepted to be on INH prophylaxis. However only 42.5% (37/87) came forward for evaluation regarding theirsuitability for INH prophylaxis. During the evaluation, eight (21.6%) of 37 otherwise asymptomatic PO were found to have active pulmonary tuberculosis (TB). Eventually only 29 PO were actually started on INH, and only 16 (55.2%) of them completed the six months course. No serious side effects were observed. One PO developed TB two months after loss to follow up before completing the six months.Conclusions: There was low acceptability of and poor compliance with INH prophylaxis among the HIV-1 infected PO despite being educated on the benefits of prophylaxis. The prevalence of PTB among asymptomatic HIV-1 infected PO was high, and therefore personswith HIV infection should be examined for TB even in the absence of symptoms

In vitro morphological studies on antibody-dependent nonimmune lymphocyte-mediated cytotoxicity in chronic active liver disease

Using an in vitro system of antibody-dependent cellular cytotoxicity (ADCC), the killing effect of chronic liver disease sera on target Chang cells, mediated by effector nonimmune lymphocytes (NLy), was studied. NLy destroyed Chang cells in monolayers pretreated with sera of patients with chronic active liver disease (CALD). Sera from these patients with CALD, after receiving steroid therapy, demonstrated a significant decrease of the cytotoxic action of NLy. The target cells treated with sera of normal subjects or patients with chronic persistent hepatitis were only minimally affected. Morphological observations of the cytotoxic action in a CALD serum-treated group showed intimate contact between NLy and the target cells in the areas of the plaques, where large numbers of the target Chang cells were injured and were closely associated with effector NLy. The Chang cells developed cytoplasmic swelling. The surface became ruffled, and intracytoplasmic organelles displayed vesicular degeneration. Thereafter, cell rupture and fragmentation occurred. The sera in patients with CALD appear to possess a membrane reactive factor, presumably antibody, against the surface membrane of Chang cells. This immunological mode of reaction between the effectors and target cells (ADCC) may be important in the perpetuation and pathogenesis of hepatocyte death in CALD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44386/1/10620_2005_Article_BF01073183.pd

Preferential Targeting of Conserved Gag Regions after Vaccination with a Heterologous DNA prime - Modified Vaccinia Ankara (MVA) boost HIV-1 vaccine regimen

Prime-boost vaccination strategies against HIV-1 often include multiple variants for a given immunogen for better coverage of the extensive viral diversity. To study the immunologic effects of this approach, we characterized breadth, phenotype, function and specificity of Gag-specific T cells induced by a DNA-prime Modified Vaccinia Ankara (MVA)-boost vaccination strategy, which uses mismatched Gag immunogens in the TamoVac 01 phase IIa trial. Healthy Tanzanian volunteers received three injections of the DNA-SMI vaccine encoding for a subtype B and AB-recombinant Gagp37 and two vaccinations with MVA-CMDR encoding subtype A Gagp55 Gag-specific T-cell responses were studied in 42 vaccinees using fresh peripheral blood mononuclear cells. After the first MVA-CMDR boost, vaccine-induced IFN-γ(+) Gag-specific T cell responses were dominated by CD4(+) T cells (compared to CD8(+) T cells, p<0.001) that co-expressed IL-2 (66.4%) and/or TNFα (63.7%). A median of 3 antigenic regions were targeted with a higher median response magnitude to Gagp24 regions - more conserved between prime and boost - as compared to regions within Gagp15 (not primed) and Gagp17 (less conserved, both p<0.0001). Four regions within Gagp24 were each targeted by 45% to 74% of vaccinees upon restimulation with DNA-SMI-Gag matched peptides. The response rate to individual antigenic regions correlated with the sequence homology between the MVA and DNA Gag encoded immunogens (p=0.04, r(2)=0.47). In summary, after the first MVA-CMDR boost, the sequence-mismatched DNA-prime MVA-boost vaccine strategy induced a Gag-specific T cell response that was dominated by polyfunctional CD4(+) T cells and that targeted multiple antigenic regions within the conserved Gagp24 Protein.IMPORTANCE Genetic diversity is a major challenge for the design of vaccines against variable viruses. While including multiple variants for a given immunogen in prime-boost vaccination strategies is one approach that aims to improve coverage for global virus variants, the immunologic consequences of this strategy have been poorly defined so far. It is unclear whether inclusion of multiple variants in prime-boost vaccination strategies improves recognition of variant viruses by T cells and by which mechanisms this would be achieved; either by improved cross-recogniton of multiple variants for a given antigenic region or rather through preferential targeting of antigenic regions more conserved between prime and boost. Engineering vaccines to induce adaptive immune responses that preferentially target conserved antigenic regions of viral vulnerability might facilitate better immune control after preventive and therapeutic vaccination for HIV and for other variable viruses

Malignant lymphomas (ML) and HIV infection in Tanzania

\ud HIV infection is reported to be associated with some malignant lymphomas (ML) so called AIDS-related lymphomas (ARL), with an aggressive behavior and poor prognosis. The ML frequency, pathogenicity, clinical patterns and possible association with AIDS in Tanzania, are not well documented impeding the development of preventive and therapeutic strategies. Sections of 176 archival formalin-fixed paraffin-embedded biopsies of ML patients at Muhimbili National Hospital (MNH)/Muhimbili University of Health and Allied Sciences (MUHAS), Tanzania from 1996-2001 were stained for hematoxylin and eosin and selected (70) cases for expression of pan-leucocytic (CD45), B-cell (CD20), T-cell (CD3), Hodgkin/RS cell (CD30), histiocyte (CD68) and proliferation (Ki-67) antigen markers. Corresponding clinical records were also evaluated. Available sera from 38 ML patients were screened (ELISA) for HIV antibodies. The proportion of ML out of all diagnosed tumors at MNH during the 6 year period was 4.2% (176/4200) comprising 77.84% non-Hodgkin (NHL) including 19.32% Burkitt's (BL) and 22.16% Hodgkin's disease (HD). The ML tumors frequency increased from 0.42% (1997) to 0.70% (2001) and 23.7% of tested sera from these patients were HIV positive. The mean age for all ML was 30, age-range 3-91 and peak age was 1-20 years. The male:female ratio was 1.8:1. Supra-diaphragmatic presentation was commonest and histological sub-types were mostly aggressive B-cell lymphomas however, no clear cases of primary effusion lymphoma (PEL) and primary central nervous system lymphoma (PCNSL) were diagnosed. Malignant lymphomas apparently, increased significantly among diagnosed tumors at MNH between 1996 and 2001, predominantly among the young, HIV infected and AIDS patients. The frequent aggressive clinical and histological presentation as well as the dominant B-immunophenotype and the HIV serology indicate a pathogenic association with AIDS. Therefore, routine HIV screening of all malignant lymphoma patients at MNH is necessary to enable comprehensive ARL diagnosis and formulation of preventive and therapeutic protocols.\u

Insulin-like growth factor-I receptor activity is essential for Kaposi's sarcoma growth and survival

Kaposi's sarcoma (KS) is a highly vascular tumour and is the most common neoplasm associated with human immunodeficiency virus (HIV-1) infection. Growth factors, in particular vascular endothelial growth factor (VEGF), have been shown to play an important role in its development. The role of insulin-like growth factors (IGFs) in the pathophysiology of different tumours led us to evaluate the role of IGF system in KS. The IGF-I receptors (IGF-IR) were identified by immunohistochemistry in biopsies taken from patients with different AIDS/HIV-related KS stages and on KSIMM cells (an established KS-derived cell line). Insulin-like growth factor-I is a growth factor for KSIMM cells with a maximum increase of 3H-thymidine incorporation of 130±27.6% (P<0.05) similar to that induced by VEGF and with which it is additive (281±13%) (P<0.05). Moreover, specific blockade of the receptor (either by α IR3 antibody or by picropodophyllin, a recently described selective IGF-IR tyrosine phosphorylation inhibitor) induced KSIMM apoptosis, suggesting that IGF-IR agonists (IGF-I and -II) mediate antiapoptotic signals for these cells. We were able to identify an autocrine loop essential for KSIMM cell survival in which IGF-II is the IGF-IR agonist secreted by the cells. In conclusion, IGF-I pathway inhibition is a promising therapeutical approach for KS tumours