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Factors influencing the population pharmacokinetic parameters of phenytoin in adult epileptic patients in South Africa.

The influence of various covariates (including weight, race, smoking, gender, age, mild-to-moderate alcohol intake, and body surface area) on the population pharmacokinetic parameters of phenytoin in adult epileptic patients in South Africa was investigated. The parameters were the maximum metabolic rate (Vm) and the Michaelis-Menten (MM) constant (Km) of phenytoin. The study population comprised 332 black and colored epileptic patients (note: "black" refers to indigenous people of South Africa, who speak one of the Bantu languages as their native language; "colored" refers to people considered to be of mixed race, classified as such by the apartheid former government of South Africa). The influence of covariates on Vm and Km estimates was determined using nonlinear mixed-effects modeling (NONMEM). Parameter models describing the factors that could potentially influence Vm and Km were tested using the Michaelis-Menten parallel MM and first-order elimination models, to which 853 steady state dose-to-serum concentration pairs were fitted. The results indicated that body weight, smoking, race, and age (65 years or older), in descending order of importance, significantly influenced Vm (p < 0.05). Although a significant difference (p = 0.03) in Km was found between black and colored patients, incorporating the influence of race in Km in the final regression model did not improve the fit of the model to the data, which indicated that the variability in Km was accounted for by Vm. The scaling factors for smoking, colored patients and age (65 years or older) in Vm were 1.16, 1.10, and 0.88, respectively. These factors should be taken into account when adjusting phenytoin dose.

Adolescent↗

The gastro-oesophageal reflux disease complex in sub-Saharan Africa.

Epidemiological and clinical studies that have reported on gastro-oesophageal reflux disease (GERD), Barrett's oesophagus, oesophageal adenocarcinoma and Helicobacter pylori infection in sub-Saharan Africa were reviewed. The data indicate that Barrett's oesophagus is rare and oesophageal adenocarcinoma uncommon in all regions of sub-Saharan Africa studied (South Africa, Ethiopia, Nigeria, Zimbabwe, Kenya and Uganda). Hiatus hernia is also uncommon. There are too few reports of GERD to allow comment. The overwhelming majority of oesophageal cancers are squamous cell type. H. pylori infection is ubiquitous with an overall prevalence of 61-100%. It is concluded that although urbanization has resulted in an increase of risk factors associated with GERD, which would be expected to lead to an increase in this disease among Africans, this increase has not happened. It is believed that the critical factor preventing GERD in black Africans is H. pylori infection, which is usually acquired in childhood, is lifelong and is probably protective for the oesophagus.

Adenocarcinoma↗

Modeling the impact of a partially effective HIV vaccine on HIV infection and death among women and infants in South Africa.

OBJECTIVE: To assess the potential impact over 10 years of a partially effective HIV vaccine in a cohort of 15-year-old adolescent girls in South Africa in terms of HIV infections and deaths prevented in mothers and infants. METHODS: A computer simulation was constructed using a population of all 15-year-old adolescent girls in South Africa followed for 10 years. A partially effective vaccine is introduced into this population with the ability to reduce the HIV incidence rates of the adolescents and vertical transmission to their infants through birth and breast-feeding. At the end of this 10 year period, the number of HIV infections and death prevented in adolescents and infants is analyzed. RESULTS: Using a 5% HIV incidence rate, a 50% effective vaccine decreases the number of HIV cases among adolescents by 57,653 (28.7%) and the number of cases among infants by 13,765 (28.9%) over 10 years. In addition, assuming a vaccine cost of $20 per dose, the vaccination program can save approximately $120 million for the South African government over 10 years. CONCLUSION: A partially effective HIV vaccine has an important role in HIV prevention in adolescents and infants in South Africa irrespective of other public policy implementations.

AIDS Vaccines↗

South Africa's "rollout" of highly active antiretroviral therapy: a critical assessment.

The number of people on highly active antiretroviral therapy (HAART) in South Africa has risen from < 2000 in October 2003, to almost 200,000 by the end of 2005. Yet South Africa's performance in terms of HAART coverage is poor both in comparison with other countries and the targets set by the government's own Operational Plan. The public-sector HAART "rollout" has been uneven across South Africa's nine provinces and the role of external assistance from NGOs and funding agencies such as the Global Fund and PEPFAR has been substantial. The National Treasury seems to have allocated sufficient funding to the Department of Health for a larger HAART rollout, but the Health Minister has not mobilized it accordingly. Failure to invest sufficiently in human resources--especially nurses--is likely to constrain the growth of HAART coverage.

Anti-HIV Agents↗

Rainfall variability in East Africa: implications for natural resources management and livelihoods.

This note examines the effects of climate variability on natural-resources management in East Africa. The bimodal rainfall regime in much of East Africa brings rainy seasons from March to May and October to December with greater interannual variability from October to December. We discuss the impacts of rainfall extremes in 1961 and 1997 and explore three examples of natural-resources management in the context of rainfall variability: inland fisheries in East and southern Africa; fluctuations in the level of Lake Victoria; and lake-shore communities around Lake Kyoga in Uganda. The discussion reflects the complexity of linkages between climate, environment and society in the region and highlights implications for natural-resources management. These range from benefits due to improved seasonal rainfall forecasting to reduce the damage of extremes, to improved understanding of existing climate-society interactions to provide insights into the region's vulnerability and adaptive capacity in relation to future climate change.

Africa, Eastern↗

Serial human passage of simian immunodeficiency virus by unsterile injections and the emergence of epidemic human immunodeficiency virus in Africa.

There is compelling evidence that both human immunodeficiency virus (HIV) types emerged from two dissimilar simian immunodeficiency viruses (SIVs) in separate geographical regions of Africa. Each of the two HIVs has its own simian progenitor and specific genetic precursor, and all of the primates that carry these SIVs have been in close contact with humans for thousands of years without the emergence of epidemic HIV. To date no plausible mechanism has been identified to account for the sudden emergence in the mid-20th century of these epidemic HIVs. In this study we examine the conditions needed for SIV to complete the genetic transition from individual human SIV infections to epidemic HIV in humans. The genetic distance from SIV to HIV and the mutational activity needed to achieve this degree of adaptation to human hosts is placed within a mathematical model to estimate the probabilities of SIV completing this transition within a single SIV-infected human host. We found that the emergence of even one epidemic HIV strain, following a single human exposure to SIV, was very unlikely. And the probability of four or more such transitions (i.e. HIV-1 groups M, O and HIV-2 subtypes A and B) occurring in a brief period is vanishingly small. We conclude that SIV cannot become a zoonosis, but requires adaptive mutations to become HIV. Some modern event must have aided in the transition of SIV to HIV. Our research indicates that serial passage of partially adapted SIV between humans could produce the series of cumulative mutations sufficient for the emergence of epidemic HIV strains. We examined the rapid growth of unsterile injections in Africa beginning in the 1950s as a biologically plausible event capable of greatly increasing serial human passage of SIV and generating HIV by a series of multiple genetic transitions. We conclude that increased unsterile injecting in Africa during the period 1950-1970 provided the agent for SIV human infections to emerge as epidemic HIV in the modern era.

Africa↗

Phylogenetic analysis of human herpesvirus-8 in South Africa and identification of a novel subgroup.

The incidence of Kaposi's sarcoma in South Africa is increasing in parallel with the human immunodeficiency virus type 1 epidemic. An 804 bp region in the ORF75 gene of 40 human herpesvirus-8 (HHV-8) isolates from South Africa was sequenced and the phylogenetic relationships were compared to published sequences. Nineteen strains clustered with subgroup B and 11 with subgroup A; however, the bootstrap values supporting these subgroups were not significant. Three strains grouped significantly with the C subgroup, while eight sequences did not cluster with any of the previously classified subgroups and were termed novel (N). The N subgroup differed from the A, B and C subgroups by DNA distances of 4.8, 4.2 and 4.5%, respectively, although within the N subgroup there was only 0.4% variation. The inclusion of this subgroup increased the number of previously described subgroup-specific polymorphisms from 17 to 47 over an 804 bp region. There was sufficient inter-subgroup genetic diversity for a single-strand conformational polymorphism assay to be used to identify them rapidly. Thus, based on analysis of the ORF75 gene, a unique HHV-8 subgroup, termed N, is present in South Africa, which accounts for 20% of circulating strains. Further studies are required to determine the degree of genetic divergence, distribution and pathogenic potential of this novel subgroup.

Adult↗

The implications of virus diversity within the SAT 2 serotype for control of foot-and-mouth disease in sub-Saharan Africa.

SAT 2 is the serotype most often associated with outbreaks of foot-and-mouth disease (FMD) in livestock in southern and western Africa and is the only SAT type to have been recorded outside the African continent in the last decade. Its epidemiology is complicated by the presence of African buffalo (Syncerus caffer), which play an important role in virus maintenance and transmission. To assess the level of genetic complexity of this serotype among viruses associated with both domestic livestock and wildlife, complete VP1 gene sequences of 53 viruses from 17 countries and three different host species were analysed. Phylogenetic analysis revealed eleven virus lineages, differing from each other by at least 20 % in pairwise nucleotide comparisons, four of which fall within the southern African region, two in West Africa and the remaining five in central and East Africa. No evidence of recombination between these lineages was detected, and thus we conclude that these are independently evolving virus lineages which occur primarily in discrete geographical localities in accordance with the FMD virus topotype concept. Applied to the whole phylogeny, rates of nucleotide substitution are significantly different between topotypes, but most individual topotypes evolve in accordance with a molecular clock at an average rate of approximately 0.002 substitutions per site per year. This study provides an indication of the intratypic complexity of the SAT 2 serotype at the continental level and emphasizes the value of molecular characterization of diverse FMD field strains for tracing the origin of outbreaks.

Africa South of the Sahara↗

Costs and health effects of breast cancer interventions in epidemiologically different regions of Africa, North America, and Asia.

We estimated the costs and health effects of treating stage I, II, III, and IV breast cancer individually, of treating all stages, and of introducing an extensive cancer control program (treating all stages plus early stage diagnosis) in three epidemiologically different world regions--Africa, North America, and Asia. We developed a mathematical simulation model of breast cancer using the stage distribution and case fatality rates in the presence and absence of treatment as predictors of survival. Outcome measures were life-years adjusted for disability (DALYs), costs (in 2000 U.S. dollars) of treatment and follow-up, and cost-effectiveness ratios (CERs; in dollars per DALY averted). Sensitivity analyses were performed to determine the robustness of the results. Treating patients with stage I breast cancer resulted in 23.41, 12.25, and 19.25 DALYs averted per patient in Africa, North America, and Asia, respectively. The corresponding average CERs compared with no intervention were 78 U.S. dollars , 1,960 U.S. dollars, and 62 U.S. dollars per DALY averted. The number of DALYs averted per patient decreased with stage; the value was lowest for stage IV treatment (0.18-0.19), with average CERs of 4,986 U.S. dollars in Africa, 70,380 U.S. dollars in North America, and 3,510 U.S. dollars per DALY averted in Asia. An extensive breast cancer program resulted in 16.14, 12.91, and 12.58 DALYs averted per patient and average CERs of 75 U.S. dollars, 915 U.S. dollars, and 75 U.S. dollars per DALY averted. Outcomes were most sensitive to case fatality rates for untreated patients, but varying model assumptions did not change the conclusions. These findings suggest that treating stage I disease and introducing an extensive breast cancer program are the most cost-effective breast cancer interventions.

Africa↗

Clinical and molecular characterization of lipoid proteinosis in Namaqualand, South Africa.

BACKGROUND: Lipoid proteinosis (LiP) is a rare autosomal recessive disorder characterized by a hoarse voice, warty skin infiltration and scarring. Mutations within the extracellular matrix protein 1 (ECM1) gene cause LiP. Since the early 1970s it has been recognized that South Africa has one of the largest groups of LiP patients worldwide, suggesting a probable founder effect. As LiP patients present with considerable clinical variability, this group of patients offers a unique opportunity for genotype-phenotype correlation. OBJECTIVES: To assess the clinical features and the molecular basis of LiP in patients from the Namaqualand area of the Northern Cape province of South Africa and to examine molecular evidence for a founder effect. SUBJECTS AND METHODS: The LiP patient cohort consisted of 29 Coloured patients from Namaqualand and a further seven Caucasoid patients from other areas of South Africa. The control group included 100 healthy geographically and ethnically matched individuals from Namaqualand. Samples were collected after informed consent and with ethics committee approval from the University of the Witwatersrand. LiP patients were examined clinically and a structured recording sheet was completed. A brief neurological evaluation was also performed. The LiP founder effect was investigated at the molecular level by ECM1 mutation detection and haplotype analysis. RESULTS: The most consistent clinical signs for a diagnosis of LiP in this group were a hoarse voice and thickened sublingual frenulum leading to restricted tongue movement. Homozygosity for a nonsense mutation in exon 7 of the ECM1 gene, Q276X, was identified in all patients (Coloured and Caucasoid). Despite this genetic homogeneity, considerable clinical variability in skin presentation and psychiatric involvement was observed. Haplotype analysis using markers from a 9.98-Mb region around the ECM1 locus confirmed the founder effect with a founder core haplotype, 19-Q276X-12 (ND1-ECM1-D1S2343), in all but four LiP-associated alleles (n = 58). A LiP carrier rate of 1 in 9 was observed among the 100 Namaqualand controls, predicting a LiP incidence of 1 in 324 in this community. CONCLUSIONS: Although several consistent clinical features in LiP patients homozygous for the Q276X mutation in the ECM1 gene were observed, there remains considerable clinical variability. This suggests the action of genetic and environmental modifiers of disease severity. Strong molecular evidence supports a single founder effect for the high prevalence of LiP in South Africans, both Coloured and Caucasoid.

Adolescent↗

The significance of secondary school education for education and training of nurses in South Africa.

This paper examines current basic nursing education in South Africa and suggests that problems in the secondary school education of Black recruits affect their later training potential as professional nurses. It reports the move towards the transfer of nurse training into higher education from 1986 in South Africa. Black nurses' learning and studying difficulties are considered in the light of their high failure rate in the South African Nursing Council qualifying examinations. It is agreed that in order to prepare the high number of qualified Black nurses required by South Africa within the tertiary education sector from 1986, special attention would need to be paid to secondary education provision for Blacks.

Black or African American↗

Working with girls living on the streets in East Africa: professionals' experiences.

AIM: This paper reports a study elucidating the meaning of caring for girls of the street, as experienced by female staff members working with street children in Eastern Africa. BACKGROUND: The phenomenon of children living on the streets is a global and escalating problem, and girls are presumed to be especially vulnerable. In East Africa, the traditional extended family system is rapidly breaking down and traditional gender values seem to remain. This was the context for investigating female carers' experience of caring for girls. METHOD: Interviews were conducted with 37 project staff members working with children living on the streets in the framework of non-governmental organizations in Kenya, Uganda and Tanzania between 1997 and 1998. Transcribed text from female interviewees (n = 13) working with girls of the street was analysed using a phenomenological-hermeneutic approach. FINDINGS: The meaning of caring for girls of the street for female professional carers in East Africa was comprehensively understood as counselling the girls to integrate the past of their adverse life stories with their present identity. Counselling meant conveying visions for a possible re-direction of the life stories, from being a girl of the street into being an accepted family girl. Caring in this context meant being squeezed between ethical demands and gender values. Experiencing frustration and powerlessness was related to gender structures in society, having to fight the grip of street culture, and a lack of professional tools. Hope and satisfaction were related to success in changing the course of life stories of girls and to seeing possibilities for contributing to empowerment of girls and community members. CONCLUSIONS: Gender issues are critical to care provided to girls of the street. Carers felt that they lacked relevant knowledge and support. Ethical aspects and gender issues in relation to professional care for vulnerable girls ought to be addressed in nursing education and practice, not only for developing countries, but also as a matter of global interest.

Adaptation, Psychological↗

Abiotic and biotic determinants of the seasonal dynamics of the tick Rhipicephalus appendiculatus in South Africa.

The creation of a generic population model for the tick Rhipicephalus appendiculatus requires a detailed, quantified understanding of the interactions of these ticks with their biotic and abiotic environment in the different parts of their range, from the tropical regions of East Africa to the temperate regions of South Africa. The much greater seasonal variation in climatic conditions, particularly temperature, further from the equator introduces variable development rates and diapause into the life cycle. Estimates of natural temperature-dependent interstadial development periods, derived from a combination of published laboratory and field data, were applied to published data on the seasonal abundance of R.appendiculatus on three farms in the Eastern Cape Province of South Africa. This enabled an assessment of which ticks of one stage give rise to which ticks of the next stage, from which (a) the onset and duration of diapause in unfed adults, and (b) seasonal interstadial mortality indices in the form of k-values, could be estimated. The contribution of biotic (tick density) and abiotic (climatic) factors as predictors of mortality at each life stage was investigated by step-wise multiple regression. Density-independent mortality at the female-to-larval stage is correlated with geographically variable climatic factors, minimum temperature at two farms and minimum relative humidity at the third. The other two stages are governed by density-dependent mortality, which, it is argued, may be caused largely by the hosts' acquired resistance to ticks. As expected on theoretical grounds, this density dependence is weaker nearer to the edge of the tick's range and for the more vulnerable immature stages.

Animals↗

Prevention of malaria during pregnancy in West Africa: policy change and the power of subregional action.

BACKGROUND: Despite a broadening consensus about the effectiveness of intermittent preventive treatment (IPTp) in preventing the adverse outcomes of malaria during pregnancy, policy change to IPTp was initially limited to East Africa. In West Africa, where the policy change process for the prevention of malaria during pregnancy started much later, IPTp has been taken up swiftly. OBJECTIVE: To describe the factors that contributed to the rapid adoption of policies to prevent malaria during pregnancy in West Africa. RESULTS AND CONCLUSION: Several factors appear to have accelerated the process: (1) recognition of the extent of the problem of malaria during pregnancy and its adverse consequences; (2) a clear, evidence-based program strategy strongly articulated by an important multilateral organization (World Health Organization); (3) subregionally generated evidence to support the proposed strategy; (4) a subregional forum for dissemination of data and discussion regarding the proposed policy changes; (5) widespread availability of the proposed intervention drug (sulfadoxine-pyrimethamine); (6) technical support from reputable and respected institutions in drafting new policies and planning for implementation; (7) donor support for pilot experiences in integrating proposed policy change into a package of preventive services; and (8) financial support for scaling up the proposed interventions.

Africa, Western↗

HLA class II disease associations in southern Africa.

Southern Africa harbors several population groups representing a diversity of gene pool origins. This provides a unique opportunity to study genetic disease predisposition in these populations against a common environmental background. Human leukocyte antigen (HLA) association studies of these populations could improve knowledge on inter-population variation and HLA-related disease susceptibility. The aim of this paper is to review HLA class II disease associations reported for southern African population groups, compare them with findings in other populations and identify those unique to southern Africa. A number of HLA class II disease associations appear to be unique to southern African populations. These include DRB1*14011 association with insulin-dependent diabetes mellitus susceptibility in the Xhosa and DRB1*10 and DQB1*0302 with rheumatoid arthritis susceptibility in the South African (SA) Indian and SA Coloreds, respectively. A noteworthy similarity in class II disease association was observed among southern African Caucasoid and their European parental populations. Unique HLA class II disease associations observed in southern Africa are consistent with the notion that unique environmental and natural selective factors have resulted in certain ethnic-specific HLA class II disease associations, while common HLA class II disease associations found across different populations support the notion that common diseases are caused by common, ancient alleles present in indigenous African populations.

Africa, Southern↗

Mortality and outcome of insulin-dependent diabetes in Soweto, South Africa.

Sixty-four insulin-dependent (Type 1) diabetic patients (IDDM) in Soweto, South Africa were followed over a 10-year period. Patients were assessed in 1982 and again in 1992. There were 10 deaths (16%), half of which were due to renal failure. Ketoacidosis, hypoglycaemia, and sepsis accounted for the rest. At the 10-year follow-up mean age (+/- SD) was 32.4 +/- 5.0 years and diabetes duration 13.6 +/- 2.6 years. Retinopathy affected 52%, peripheral neuropathy 42%, and nephropathy 28% (all significantly increased from the 1982 assessment). Microalbuminuria and autonomic neuropathy were also common. Serum cholesterol was over 6.5 mmol l-1 in 19%, hypertension affected 22%, and 28% were cigarette smokers; though no patient had evidence of macroangiopathy. We conclude that IDDM in South Africa is associated with excess mortality, a significant proportion of which is related to nephropathy. Diabetes of long duration is now not uncommon in South Africa, and although diabetic complications frequently occur, most patients have good life quality and freedom from large vessel disease.

Adolescent↗

Obesity in South Africa.

South Africa has not been spared in the rampant global increase in obesity. Throughout Africa, as elsewhere, ethnicity has a major impact on the incidence and pathogenesis of comorbid diseases, particularly diabetes. Combined figures for obesity and overweight (body mass index [BMI] > 25 kg m(-2)) obtained across all ethnic groups in the adult population in 1998, were 57% for women and 29% for men. From the 1960s until the late 1980s, the notion of 'healthy' or 'benign' obesity was propagated in South Africa. Not surprisingly, this led to ignorance around the problem of obesity, and treatment of some of the comorbid diseases was neglected. Fortunately, as an increasing number of seminal studies draw us closer to reality, the misperception of benign obesity is being corrected. This is allowing us to address the real issues underlying the current epidemic, and to recognize and manage the comorbid diseases, in particular type 2 diabetes. A new framework for research is also emerging as we begin to define the factors underlying the impact of ethnicity on obesity.

Body Mass Index↗

Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Caribbean.

OBJECTIVE: To present estimates of maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Caribbean, and to discuss strategies to prevent these deaths. DESIGN: Retrospective review of all available data. SETTING: Database of the World Health Organization's Maternal Health and Safe Motherhood Programme. MAIN OUTCOME MEASURES: Estimates of the total maternal mortality and the proportions of deaths associated with hypertensive disorders of pregnancy. RESULTS: Estimates of mortality associated with hypertensive disorders of pregnancy were similar in Africa, Latin America and the Caribbean, despite considerably higher total mortality in Africa. Variations in both overall mortality and that associated with hypertensive disorders of pregnancy were greatest in Asia. Despite their limitations, these data suggest that between 10-15% of maternal deaths are associated with hypertensive disorders of pregnancy, and that 10% are associated with eclampsia. CONCLUSIONS: Where maternal mortality is relatively high, the excess is likely to be due to a high mortality associated with haemorrhage and infection and reductions are most likely to come from reductions in these deaths. Evidence from both developed and developing countries suggests that deaths associated with hypertensive disorders of pregnancy are the most difficult to prevent. More rigorous assessment of interventions designed to prevent these deaths is urgently required.

Africa↗