Serotyping and genotyping of HIV-1 infection in residents of Khayelitsha, Cape Town, South Africa.

It is estimated that between 5.5 and 6.1 million people are infected with HIV/acquired immunodeficiency syndrome (AIDS) in South Africa, with subtype C responsible for the majority of these infections. The Khayelitsha suburb of Cape Town has one of the highest HIV prevalence rates in South Africa. Overcrowding combined with unemployment and crime in parts of the area perpetuates high-risk sexual behavior, which increases exposure to infection by HIV. Against this background, the objective of this study was to characterize HIV-1 in residents confirmed to be seropositive. Serotyping was performed through a competitive enzyme-linked immunosorbent assay (cPEIA). Genotyping methods included RNA isolation followed by RT-PCR and sequencing of the gag p24, env gp41 immunodominant region (IDR), and env gp120 V3 genome regions of HIV-1. With the exception of a possible C/D recombinant strain, all HIV-1 strains were characterized as HIV-1 group M subtype C. One individual was shown to harbor multiple strains of HIV-1 subtype C. In Southern Africa, the focus has been to develop a subtype C candidate vaccine, as this is the major subtype found in this geographical area. Therefore, the spread of HIV-1 and its recombinant strains needs to be monitored closely.

Respiratory atopic disease, Ascaris-immunoglobulin E and tuberculin testing in urban South African children.

BACKGROUND: Epidemiological relation of intestinal helminth infection and atopic disease, both associated with a T-helper (Th) 2 immune response, is controversial, as it has been reported that helminth infection may either suppress or pre-dispose to atopic disease. This relation has not been tested in an area with a high burden of Mycobacterium tuberculosis (MTB) infection, a known Th1-stimulating infection. OBJECTIVE: To study the association of intestinal helminth infection and atopic disease in a community where helminth infection is endemic and MTB infection is high. METHODS: Three-hundred and fifty-nine randomly selected children aged 6-14 years from a poor urban suburb were tested with allergy questionnaire, skin prick test (SPT) to common aeroallergens, Ascaris-specific IgE (Ascaris-sIgE), fecal examination for pathogenic intestinal helminths and tuberculin skin testing (TST). Histamine bronchoprovocation was tested in the group of children aged 10 years and older. RESULTS: were corrected for demographic variables, socioeconomic status, parental allergy, environmental tobacco smoke (ETS) exposure in the household, recent anthelminthic treatment and for clustering in the sampling unit. Results Ascaris-sIgE was elevated in 48% of children, Ascaris eggs were found in 15% and TST was positive in 53%. Children with elevated Ascaris-sIgE had significantly increased risk of positive SPT to aeroallergens, particularly house dust mite, atopic asthma (ever and recent), atopic rhinitis (ever and recent) and increased atopy-related bronchial hyper-responsiveness. In children with negative TST (<10 mm), elevated Ascaris-sIgE was associated with significantly increased risk of atopic symptoms (adjusted odds ratio (OR(adj)) 6.5; 95% confidence interval (CI) 1.9-22.4), whereas in those with positive TST (>/=10 mm) this association disappeared (OR(adj) 0.96; 95% CI 0.4-2.8). CONCLUSIONS: These results suggest that immune response to Ascaris (Ascaris-sIgE) may be a risk factor of atopic disease in populations exposed to mild Ascaris infection and that MTB infection may be protective against this risk, probably by stimulation of anti-inflammatory networks.

Efficacy of albendazole against the whipworm trichuris trichiura--a randomised, controlled trial.

OBJECTIVES AND DESIGN: To test the efficacy of albendazole against the whipworm Trichuris trichiura for school-based deworming in the south-western Cape, South Africa. Children infected with Trichuris were randomised to 3 doses of albendazole (400, 800 or 1200 mg), each repeated 4 times. The boy/girl ratio was 1. A group not infected with worms was treated with placebo, creating a negative control. SUBJECTS AND SETTING: Pupils at a primary school serving a wine-producing area approximately 90 km east of Cape Town. OUTCOME MEASURES: Trichuris cure rates and reduction in the number of eggs/g in faeces, as well as the infection dynamics of Trichuris and Ascaris during treatment with placebo. RESULTS: Albendazole treatment was associated with Trichuris cure rates of 23% (400 mg), 56% (800 mg) and 67% (1200 mg) after the final treatment. The corresponding reductions in the number of eggs/g of faeces were 96.8%, 99.3% and 99.7%. Environmental pollution by human faeces was confirmed because worm egg-negative children in the placebo group became egg-positive while the study was in progress. CONCLUSION: The 400 mg stat dose had a low Trichuris cure rate. To repeat the dose on 2 or 3 days would increase cost, reduce compliance and complicate management. Albendazole cannot be used in deworming programmes in South Africa because it is a Schedule 4 prescription medicine. De-scheduling is needed urgently, particularly because of high efficacy against hookworm in KwaZulu-Natal and neighbouring countries.

Atherosclerosis: aortic lipid changes induced by diets suggest diffuse disease with focal severity in primates that model human atheromas.

Atherosclerosis in Vervet or African Green monkeys (Cercopithecus aethiops) models the morphology and cytology of the disease of humans, and it is well established that the rate of atherogenesis in Vervets is influenced by diet. Aortic intimal concentrations of lipids and phospholipids known to be major components of atheromas were determined in female Vervets fed for 4 years on either an atherogenic (AD) or a prudent Western diet (PD). Lipid concentrations detectable microscopically as cholesterol crystals and foam cells were confirmed biochemically. In addition, the AD was associated with diffuse, invisible accumulation of lipids throughout aortic tissue to the extent that tissue with no fatty streaks or plaque (AD) contained the same or more lipids than visible fatty streaks (PD). Correlations between lipid concentrations and atherosclerosis were highly positive, which supports known correlations between aortic, plasma, and dietary lipids during atherogenesis, and validates the aortic lipid analysis. These aortic lipid concentration results imply that atherosclerosis is not confined to focal pathologic anatomy, but in terms of lipid components of the disease, it develops throughout the arterial system of Old World omnivorous primates. If the results are applicable to people, they provide new insight and emphasize the need to minimize dietary sources of atherogenic lipids.

Vervet monkeys and whole-food diets for studying the effects of dietary lipids on plasma lipoprotein metabolism and atherosclerosis.

It is well established that some species of nonhuman primates are models of choice for polygenic hyperlipoproteinaemia and atherosclerosis induced and promoted by diets as occur in man. The Vervet monkey (Cercopithecus aethiops) has proved to be one such model. Our group has used this model extensively to determine the effects of a variety of dietary lipid components on plasma lipoprotein metabolism and atherosclerosis against a background of a Western atherogenic or prudent diet. The diets fed in all these studies were formulated entirely from cooked foods that are normal components of Westernised diet with no extra synthetic cholesterol added. This model has been used successfully to evaluate the effect of fish oil, amount and degree of dietary fat unsaturation and w-6/w-3 fatty acid ratio and lipid-lowering agents on plasma lipoprotein metabolism and atherosclerosis. Dietary manipulation in this model is simple, relatively inexpensive and offers almost unlimited options for future dietary intervention studies.

Confirmation of efficacy of etofibrate against peripheral atherosclerosis in non-human primates which model human lesion types I-VII.

In dyslipidemic or hyperlipidemic patients etofibrate (CAS 31637-97-5, active principle of Lipo-Merz-retard) improves plasma lipoprotein profiles by reducing low density lipoprotein cholesterol and triglycerides. Experimentally, it also promotes fibrinolysis and thrombolysis and reduces the susceptibility of lipoproteins to oxidative stress. In order to investigate the possible efficacy of etofibrate on atherosclerosis, a study in African Green Monkeys was performed. To accelerate atherogenesis, balanced groups of adult male Vervetes (Cercopithecus aethiops) were fed an atherogenic diet, with and without etofibrate, while negative controls received a prudent diet. Total dietary risk exposure was 38 months, with etofibrate treatment during the final 27 months. The etofibrate dose achieved plasma concentrations of clofibric acid comparable to the one achieved clinically. Necropsy demonstrated lesions equivalent to human atherosclerosis types I-VII, which were compared between treatments both macroscopically and microscopically. Peripheral atherosclerosis was significantly less frequent after etofibrate treatment than in positive controls. In aortas, etofibrate probably ameliorated atherogenesis, as defined by proliferation of smooth muscle and foam cells, and accumulation of cholesterol crystals. Effective reduction of plasma cholesterol by etofibrate was confirmed. In conclusion, anti-atherogenic efficacy of etofibrate was demonstrated in a non-human primate model of accelerated atherogenesis. The results on peripheral atherosclerosis confirm the preliminary clinical data in patients suffering from peripheral vascular occlusion.