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BACKGROUND AND METHODS: A retrospective study of the national health profile of Eritreans, focusing on acute respiratory tract infection (ARTI), tuberculosis (TB), diarrhoea, sexually transmitted diseases (STDs) and HIV/AIDS, was done on data from 1998 to 2003 through a health information management system. Records were included for patients of all ages receiving outpatient and inpatient hospital services during the study period. All incidence rates were given as cases per 100,000 population. RESULTS: The incidence of ARTI increased from 6,500 cases per annum in 1998 to 8 500 in 2003, representing a 30% increase. Diarrhoea rates remained unchanged, averaging 3,000 cases. For both ARTI and diarrhoea, rates were at least 3 times higher in children under 5 years of age than in those over 5 years of age. The incidences of TB and STDs decreased from 370 and 220 in 1998 to 170 and 80 in 2003, respectively. HIV/AIDS incidence increased from 40 in 1998 to 65 in 2003, reflecting a 60% increase. The case fatality rates (CFRs) for HIV/AIDS and TB were 12% and 2% in 1998, increasing to 14% and 3%, respectively, in 2001. The CFR for ARTI and diarrhea remained low at 0.3%. CFRs were higher in children under 5 years than in those over 5 years for all the diseases but rates declined consistently, probably reflecting the positive impact of the introduction of the integrated management of childhood illness (IMCI). Although the incidence rate of HIV/AIDS was relatively low compared with rates for TB, ARTI and diarrhoea, the HIV/AIDS CFR was relatively high, posing a threat to the gains made in control of infectious diseases. The disease burden from TB and STDs declined over the 6-year study period, while that from ARTI and HIV/AIDS increased. Consequently the overall disease burden from communicable diseases remained unchanged over the study period.

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The prevalence of cardiovascular diseases has been shown to be on the increase in Africa based on hospital-based information and limited national surveys. A recent report on analysis of data from Health Information Management Systems (HIMS) highlighted an increasing burden of noncommunicable diseases (NCDs) in Eritrea, with the incidence of hypertension doubling in a space of 6 years. HMIS data are only a proxy of national prevalence rates, necessitating the conduct of national surveys. The WHO STEPwise approach to surveillance of NCDs was used for the national NCD risk factor survey in 2004. This report focuses on blood pressure (BP) and obesity (body mass index (BMI) > 30 kg/m2) as NCD risk factors in Eritrea. A total of 2352 people in age groups 15 to 64 years participated in the survey. The prevalence of hypertension defined as BP > 140/90 mmHg was 15.9% in the general population, with 16.4% in urban and 14.5% in rural areas, 17% of whom were males while 15% were females. BMI was positively associated with systolic (SBP), diastolic and mean arterial pressure. Although the prevalence of obesity (3.3%) was higher in females, the effect of BMI on BP was higher in males than in females (regression coefficient 0.64 and 0.38, respectively, P < or = 0.05), especially in those >45 years. BMI did not have a significant effect on BP in lean people (BMI < 19) and in those with high BMI, but was positively correlated to SBP in those with normal BMI (P < or = 0.02). BMI and age appear to play a synergistic role in creating a strong association with BP.

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Cigarette smoke is known to induce cytochrome P4501A1 expression and activity in a variety of species. Although the elevation of this isozyme is assumed to be associated with the activation of the CYP1A1 gene through a ligand-mediated mechanism involving the Ah-receptor (AhR), this has not been determined. In this study we have examined the mechanism by which an ambient level of aged and diluted sidestream cigarette smoke (ADSS) induces cytochrome P4501A1. Effects of ADSS on C57BL/6N and DBA/ 2N mice were examined. Induction of P4501A1-associated ethoxyresorufin-O-dealkylase (EROD) activity was observed in the lungs of C57BL/6N mice, while there was no induction in DBA/ 2N mice. ADSS also induced EROD in wild-type mouse hepatoma (Hepa1c1c7) cells (hepa1), but not in variant hepa1 cells defective in the AhR nuclear translocator (ARNT) protein. ADSS exposure of recombinant hepa1 cells, stably transfected with a reporter plasmid containing the luciferase gene under control of several dioxin responsive enhancers (DREs), resulted in a time- and exposure-dependent induction of luciferase activity. ADSS-mediated induction of luciferase activity was inhibited by alpha-naphthoflavone (alpha NF), an Ah-receptor antagonist. Gel retardation analysis demonstrated that exposure to ADSS induced transformation and DNA binding of the AhR complex. In summary, our results not only indicate a role for the AhR in mediating the induction of P4501A1 by ADSS, but also demonstrate that environmentally relevant levels of ADSS must contain AhR ligands at sufficient concentrations to activate gene expression in an AhR-dependent manner.

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Earlier studies have shown that both mainstream and sidestream cigarette smoke increase the activities of cytochrome P4501A1 and 2E1 in the lungs of adult animals; however, little information is available on the influence of ambient levels of sidestream cigarette smoke on cytochrome P450 monooxygenase activity in the developing lung. The present studies were conducted to define the developmental profiles of cytochrome P450 monooxygenases 1A1 and 2B1 in rat lung and liver and to assess the effects of aged and diluted sidestream cigarette smoke (ADSS) on the developmental profile of these two enzymes. Accordingly, pulmonary and hepatic microsomal P4501A1 and 2B1 activities were determined by measuring ethoxy- and pentoxyresorufin-O-delakylase (EROD and PROD, respectively) activity in animals exposed to filtered air or ADSS from birth to 7, 14, 21, 50, and 100 days of age. Pulmonary P4501A1 activity in control rats was not detected until 14 days of age. Activities increased threefold between 14 and 21 days of age and remained unchanged to 100 days of age. In animals exposed to ADSS from birth, pulmonary EROD activities were detected as early as 7 days postnatal and were elevated three- to fourfold above control at all other ages examined. Hepatic EROD activities were unaltered by ADSS exposure. Short-term (4-day) ADSS exposure was as effective in upregulating pulmonary microsomal EROD activities as 100-day exposures. Induction of pulmonary EROD activities and the associated increases in mRNA levels were dependent upon the particulate fraction. Stimulation of EROD activities in major and minor daughter subcompartments was three- to fourfold higher in ADSS-exposed animals compared to controls, while there was no induction in the trachea and less than a twofold increase in the parenchyma. Pulmonary PROD activities developed more slowly than EROD and did not reach adult levels until Day 50. ADSS did not alter pulmonary or hepatic PROD activities. These studies show that P4501A1 and 2B1 develop at different rates in rat lung and liver and that exposure to ADSS markedly increases P4501A1 activities in the lung at all ages examined.

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Because a number of studies suggest that the developmental expression of cytochrome P-450s (CYP) in Clara cells is species specific, this study was designed to compare the developmental patterns of the isoform CYP2B and NADPH reductase protein expression and CYP2B activity with the time course of smooth endoplasmic reticulum (SER) formation in Clara cells of rat lung. Pulmonary CYP2B activity measured as pentoxyresorufin O-dealkylation in lung homogenates was not detectable before 7 days postnatal age, but was detectable at adult levels at 50 days postnatal age. In Clara cells, CYP2B and NADPH reductase were detected immunohistochemically at 4 days postnatal age and at adult levels at 10 days postnatal age. The volume density of SER in Clara cells of terminal bronchioles measured morphometrically increased significantly with postnatal age. We conclude that in the rat 1) CYP2B and NADPH reductase distribution and CYP2B activity are age dependent; 2) the increase in Clara cell SER precedes the expression of CYP2B protein; 3) cellular appearance of CYP2B protein precedes CYP activity; and 4) SER appearance and P-450 protein expression do not occur uniformly in differentiating Clara cells, even within the same bronchiole.

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M.1 monoclonal antibody has previously been shown to passively transfer partial resistance to schistosome infection within mice and to recognize a 28-kDa antigen that has peptide sequence homology with triose-phosphate isomerase (TPI; D-glyceraldehyde-3-phosphate ketol-isomerase, EC 5.3.1.1). We have now isolated the complete coding DNA for Schistosoma mansoni TPI and confirmed that this cDNA encodes the 28-kDa antigen recognized by M.1. The predicted translation product has strong homology with other TPIs, particularly from higher eukaryotes, and the sequence homology is greatest in regions known to form the active site. The complete coding DNA has been expressed within an Escherichia coli host to produce high levels of soluble, recombinant S. mansoni TPI protein. The product is recognized and purified by the M.1 antibody and is a functional TPI with an intrinsic specific activity comparable to that of rabbit and yeast TPI.

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mAb M.1 was previously shown to recognize a 28-kDa Ag in all stages of the human helminth parasite, Schistosoma mansoni, and to bind to the surface membranes of newly transformed schistosomula in a transient manner. Here we demonstrate that M.1 passively transfers partial resistance (41-49%) to cercarial challenge in naive mice. Thus, the 28-kDa Ag recognized by M.1 is a putative vaccine candidate. After immunoaffinity purification, tryptic digests of the 28-kDa Ag were prepared and individual peptides were sequenced. Amino terminus sequences of tryptic peptides of the 28-kDa Ag had high (79-87%) sequence homology with the mammalian glycolytic/gluconeogenic enzyme triosephosphate isomerase (TPI). Purified, native 28-kDa Ag from adult parasites was shown to function enzymatically in an analogous manner to yeast and mammalian TPI in the reverse reaction. Addition of M.1 antibody to the enzyme reaction altered the catalytic activity of schistosome TPI. To determine the immunologic cross-reactivity of this vaccine candidate with mammalian TPI, Western blot analysis was performed and demonstrated that M.1 was immunologically specific for the schistosome enzyme.

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Murine T cell lines responsive to the protozoan parasite Trypanosoma cruzi were generated in vitro by stimulating hyperimmune C57BL/6 lymphoid cells with trypomastigote stage antigen. A spleen-derived line designated ST1 and eight clones derived from ST1 were characterized. All lines bear the surface phenotype Thy-1.2+, Ly-1.2+, 2.2- and respond to T. cruzi antigen only in the presence of antigen-presenting cells matched at the I-A subregion of the H2 locus. Clonal specificity analyses indicated that these T. cruzi-selected T cells are species specific and recognize antigenic determinants that are expressed predominantly in the trypomastigote stage. On the basis of their distinct patterns of response to a panel of different T. cruzi strains, clones recognizing strain-specific, shared, or common determinants were identified. Functional studies indicated that ST1 and some but not all of the clones are capable of expressing antigen-specific T helper function in vitro and in vivo. In addition, co-incubation of T. cruzi-specific T cells with cultured T. cruzi-infected syngeneic macrophages led to the dose-dependent destruction of intracellular parasites. Most notably, ST1 and several of the cloned T. cruzi-specific T cell lines were able to passively protect syngeneic recipients from lethal T. cruzi challenge infection. Efforts to identify the parasite antigens recognized by these T cell lines, particularly the protective clones, are currently in progress.

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Mice deficient in dietary vitamin E are impaired in their humoral and cell-mediated immunological responses. The basis for this impaired immunocompetence was investigated by using the in vitro antibody response as an assay system. Spleen cells from mice fed vitamin E-deficient diets were low responders to the antigens, sheep red blood cells (SRBC) and dinitrophenyl-L-lysine-Ficoll (DNP-Ficoll). However, they responded as well as mice fed vitamin E-supplemented diets to the relatively macrophage-independent antigen trinitrophenylated-lipopolysaccharide (TNP-LPS). This suggested that the macrophage was the cell most affected by the vitamin E deficiency. The involvement of macrophages was confirmed directly by mixing experiments, in which it was shown that macrophages from vitamin E-deficient mice were unable to support an antibody response by macrophage-depleted spleen cells from vitamin E-supplemented mice. Macrophages from vitamin E-deficient mice expressed less Ia antigen, and seemed less able to present antigen to nonadherent cells. However, it was found that macrophages from vitamin E-deficient mice not only lacked accessory cell function, but could act instead as suppressor cells. The effect of dietary vitamin E was noted with either saturated or unsaturated sources of fat in the diet.

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