Hepatitis B Virus Infection in Human Immunodeficiency Virus Infected Southern African Adults: Occult or Overt – That Is the Question

Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share transmission routes and are endemic in sub-Saharan Africa. The objective of the present study was to use the Taormina definition of occult HBV infection, together with stringent amplification conditions, to determine the prevalence and characteristics of HBV infection in antiretroviral treatment (ART)-naïve HIV^+ve adults in a rural cohort in South Africa. The presence of HBV serological markers was determined by enzyme linked immunoassay (ELISA) tests. HBV DNA-positivity was determined by polymerase chain reaction (PCR) of at least two of three different regions of the HBV genome. HBV viral loads were determined by real-time PCR. Liver fibrosis was determined using the aspartate aminotransferase-to-platelet ratio index. Of the 298 participants, 231 (77.5%) showed at least one HBV marker, with 53.7% HBV DNA^−ve (resolved) and 23.8% HBV DNA^+ve (current) [8.7% HBsAg^+ve: 15.1% HBsAg^−ve]. Only the total number of sexual partners distinguished HBV DNA^+ve and HBV DNA^−ve participants, implicating sexual transmission of HBV and/or HIV. It is plausible that sexual transmission of HBV and/or HIV may result in a new HBV infection, superinfection and re-activation as a consequence of immunesuppression. Three HBsAg^−ve HBV DNA^+ve participants had HBV viral loads <200 IU/ml and were therefore true occult HBV infections. The majority of HBsAg^−ve HBV DNA^+ve participants did not differ from HBsAg^+ve HBV DNA^+ve (overt) participants in terms of HBV viral loads, ALT levels or frequency of liver fibrosis. Close to a quarter of HIV^+ve participants were HBV DNA^+ve, of which the majority were HBsAg^−ve and were only detected using nucleic acid testing. Detection of HBsAg^−ve HBV DNA^+ve subjects is advisable considering they were clinically indistinguishable from HBsAg^+ve HBV DNA^+ve individuals and should not be overlooked, especially if lamivudine is included in the ART.     

Containing political instability in a poly‐ethnic society: The case of Mauritius

In a continent whose political record has been largely marred by almost three decades of post‐independence political turmoil verging on genocidal proportions, the small state of Mauritius has devised a sociopolitical system that has largely succeeded in containing some of the worst excesses of bloody political confrontation usually associated with poly‐ethnic societies, for example, the Nigerian Civil War of the 1960s; the Tutsi/Hutu conflict in Burundi in 1988–89, and so on. In this article it is argued that Mauritius has devised and maintained a three‐pronged strategy to safeguard political stability, namely: (1) the adoption of constitutional safeguards to accommodate ethnic divisions; (2) a spoils system of (ethnic) parliamentary representation designed to ensure that no section of the population is alienated, thereby respiting in the politicization of ethnic divisions; (3) a ‘national patronage’ system through which massive social welfare spending has been maintained since independence. This has functioned to dampen the possibility of political violence nourished by general poverty and the resultant alienation. Finally, the commitment of the various ruling coalitions to the parliamentary process has had the effect of impelling the major opposition parties to seek to gain power through peaceful constitutional means rather than through violent political confrontation.     

Using BD Vacutainer CD4 Stabilization Tubes for Absolute Cluster of Differentiation Type 4 Cell Count Measurement on BD FacsCount and Partec Cyflow Cytometers: A Method Comparison Study from Zimbabwe

Background

Blood collected in conventional EDTA tubes requires laboratory analysis within 48 hours to provide valid CD4 cell count results. This restricts access to HIV care for patients from rural areas in resource-constraint settings due to sample transportation problems. Stabilization Tubes with extended storage duration have been developed but not yet evaluated comprehensively.

Objective

To investigate stability of absolute CD4 cell count measurement of samples in BD Vacutainer CD4 Stabilization Tubes over the course of 30 days.

Methods

This was a laboratory-based method comparison study conducted at a rural district hospital in Beitbridge, Zimbabwe. Whole peripheral blood from 88 HIV positive adults was drawn into BD Vacutainer CD4 Stabilization Tubes and re-tested 1, 2, 3, 5, 7, 14 and 30 days after collection on BD FacsCount and Partec Cyflow cytometers in parallel. Absolute CD4 cell levels were compared to results from paired samples in EDTA tubes analysed on BD FacsCount at the day of sample collection (references methodology). Bland-Altman analysis based on ratios of the median CD4 counts was used, with acceptable variation ranges for Limits of Agreements of +/-20%.

Results

Differences in ratios of the medians remained below 10% until day 21 on BD FacsCount and until day 5 on Partec Cyflow. Variations of Limits of Agreement were beyond 20% after day 1 on both cytometers. Specimen quality decreased steadily after day 5, with only 68% and 40% of samples yielding results on BD FacsCount and Partec Cyflow at day 21, respectively.

Conclusions

We do not recommend the use of BD Vacutainer CD4 Stabilization Tubes for absolute CD4 cell count measurement on BD FacsCount or Partec Cyflow due to large variation of results and decay of specimen quality. Alternative technologies for enhanced CD4 testing in settings with limited laboratory and sample transportation capacity still need to be developed.     

Access to CD4 Testing for Rural HIV Patients: Findings from a Cohort Study in Zimbabwe

Background

CD4 cell count measurement remains an important diagnostic tool for HIV care in developing countries. Insufficient laboratory capacity in rural Sub-Saharan Africa is frequently mentioned but data on the impact at an individual patient level are lacking. Urban-rural discrepancies in CD4 testing have not been quantified to date. Such evidence is crucial for public health planning and to justify new yet more expensive diagnostic procedures that could circumvent access constraints in rural areas.

Objective

To compare CD4 testing among rural and urban HIV patients during the first year of treatment.

Methods

Records from 2,145 HIV positive adult patients from a Médecins sans Frontières (Doctors without Borders) HIV project in Beitbridge, Zimbabwe, during 2011 and 2012 were used for a retrospective cohort analysis. Covariate-adjusted risk ratios were calculated to estimate the effects of area of residence on CD4 testing at treatment initiation, six and 12 months among rural and urban patients.

Findings

While the proportion of HIV patients returning for medical consultations at six and 12 months decreased at a similar rate in both patient groups, CD4 testing during consultations dropped to 21% and 8% for urban, and 2% and 1% for rural patients at six and 12 months, respectively. Risk ratios for missing CD4 testing were 0.8 (95% CI 0.7-0.9), 9.2 (95% CI 5.5-15.3), and 7.6 (95% 3.7-17.1) comparing rural versus urban patients at treatment initiation, six and 12 months, respectively.

Conclusions

CD4 testing was low overall, and particularly poor in rural patients. Difficulties with specimen transportation were probably a major factor underlying this difference and requires new diagnostic approaches. Our findings point to severe health system constraints in providing CD4 testing overall that need to be addressed if effective monitoring of HIV patients is to be achieved, whether by alternative CD4 diagnostics or newly-recommended routine viral load testing.     

Hepatocyte growth factor/scatter factor suppresses TNF-alpha-induced E-selectin expression in human umbilical vein endothelial cells

Induction of E-selectin on endothelial cell surface initiates leukocyte adhesion and subsequent migration into the subendothelium. Here, we tested the effect of hepatocyte growth factor (HGF) on inflammatory cytokine-induced expression of E-selectin and consequent leukocyte-endothelial cell interaction using human umbilical vein endothelial cells (HUVEC). Prior treatment of HUVEC with HGF significantly attenuated the tumor necrosis factor (TNF)-alpha-induced E-selectin protein, adhesion of HL60 cells to HUVEC and E-selectin mRNA expression in a dose-dependent manner, while HGF itself did not exert any effects. The HGF effects on the mRNA expression were inhibited in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, which also abolished HGF-stimulated eNOS activity. These results suggest HGF plays cardiovascular protective functions mediated, at least in part, through nitric oxide-dependent suppression of inflammatory cytokine-induced E-selectin expression and subsequent tethering of leukocytes to endothelial cells.     

Norepinephrine stimulates interleukin-6 mRNA expression in primary cultured rat hepatocytes

Non-invasive immobilization stress causes an increase in the plasma interleukin (IL)-6 level accompanied by increased IL-6 mRNA expression and IL-6 immunoactivity in the liver [Biochem. Biophys. Res. Commun. (1997) 238, 707-711]. In the present study, using rat primary cultured hepatocytes and non-parenchymal liver cells, the effect of norepinephrine (NE) on IL-6 mRNA expression was determined. IL-6 mRNA expression in hepatocytes, but not in non-parenchymal liver cells, increased when the cells were treated with NE. The stimulatory effect of NE was inhibited by the combined use of alpha- and beta-adrenergic antagonists. IL-6 mRNA expression in hepatocytes also increased on incubation with the culture medium of non-parenchymal liver cells treated with NE. The effect of the medium was blocked by an IL-1 receptor antagonist. Moreover, exogenous IL-1beta stimulated IL-6 mRNA expression in hepatocytes. IL-1beta was present in the medium of non-parenchymal liver cells and increased with NE-treatment. These results suggest that NE released from sympathetic nerve terminals during stress can directly increase IL-6 mRNA expression in hepatocytes and indirectly through IL-1beta production from non-parenchymal liver cells.