Infant mortality in Zambia: socioeconomic and demographic correlates

Trends in infant mortality in Zambia suggest a reversal of the decline experienced between the 1960s and the late 1970s. From a high of about 140, infant mortality rate declined to about 90 in the late 1970s only to rise again to 100 by 1996. Data on 5,600 births born between 1987 and 1992, and 6,630 births between 1991 and 1996 from the Zambian DHS are analyzed to identify socioeconomic and demographic correlates of infant mortality. Demographic factors such as small size at birth and short birth intervals are associated with higher neonatal mortality. In the post-neonatal period, urban children from poorer households had the highest mortality between 1991-1996. Also, differences in infant mortality rates between provinces narrowed. Children born in the most developed province of Lusaka had as high of risk of dying as those from Luapula, a province with a history of extremely high mortality rates in Zambia.     

Estimated HIV Trends and Program Effects in Botswana

Background

This study uses surveillance, survey and program data to estimate past trends and current levels of HIV in Botswana and the effects of treatment and prevention programs.

Methods/Principal Findings

Data from sentinel surveillance at antenatal clinics and a national population survey were used to estimate the trend of adult HIV prevalence from 1980 to 2007. Using the prevalence trend we estimated the number of new adult infections, the transmission from mothers to children, the need for treatment and the effects of antiretroviral therapy (ART) and adult and child deaths. Prevalence has declined slowly in urban areas since 2000 and has remained stable in rural areas. National prevalence is estimated at 26% (25–27%) in 2007. About 330,000 (318,000–335,000) people are infected with HIV including 20,000 children. The number of new adult infections has been stable for several years at about 20,000 annually (12,000–26,000). The number of new child infections has declined from 4600 in 1999 to about 890 (810–980) today due to nearly complete coverage of an effective program to prevent mother-to-child transmission (PMTCT). The annual number of adult deaths has declined from a peak of over 15,500 in 2003 to under 7400 (5000–11,000) today due to coverage of ART that reaches over 80% in need. The need for ART will increase by 60% by 2016.

Conclusions

Botswana''s PMTCT and treatment programs have achieved significant results in preventing new child infections and deaths among adults and children. The number of new adult infections continues at a high level. More effective prevention efforts are urgently needed.     

Impact of non-HIV and HIV risk factors on survival in HIV-infected patients on HAART: a population-based nationwide cohort study

Background

We determined the impact of three factors on mortality in HIV-infected patients who had been on highly active antiretroviral therapy (HAART) for at least one year: (1) insufficient response to (HAART) and presence of AIDS-defining diseases, (2) comorbidity, and (3) drug and alcohol abuse and compared the mortality to that of the general population.

Methodology/Principal Findings

In a Danish nationwide, population-based cohort study, we used population based registries to identify (1) all Danish HIV-infected patients who started HAART in the period 1 January 1998–1 July 2009, and (2) a comparison cohort of individuals matched on date of birth and gender (N = 2,267 and 9,068, respectively). Study inclusion began 1 year after start of HAART. Patients were categorised hierarchically in four groups according to the three risk factors, which were identified before study inclusion. The main outcome measure was probability of survival from age 25 to 65 years. The probability of survival from age 25 to age 65 was substantially lower in HIV patients [0.48 (95% confidence interval (CI) 0.42–0.55)] compared to the comparison cohort [0.88 (0.86 to 0.90)]. However, in HIV patients with no risk factors (N = 871) the probability of survival was equivalent to that of the general population [0.86 (95% CI 0.77–0.92)]. In contrast, the probability of survival was 0.58 in patients with HIV risk factors (N = 704), 0.30 in patients with comorbidities (N = 479), and 0.03 in patients with drug or alcohol abuse (N = 313).

Conclusions

The increased risk of death in HIV-infected individuals is mainly attributable to risk factors that can be identified prior to or in the initial period of antiretroviral treatment. Mortality in patients without risk factors on a successful HAART is almost identical to that of the non–HIV-infected population.     

IFN-gamma production in rabbits: behavioral and endocrine correlates

Freely interacting male rabbits were studied to establish the effect of exogenous testosterone on interferon-gamma (IFN-gamma) production in peripheral blood mononuclear cells (PBMCs) and to evaluate if this effect is related to season, social rank, plasma corticosterone and glucocorticoid receptors (GcR) in PBMCs. Dominance behavior increases after testosterone propionate (TP) administration only in rank 1 animals, while submission behavior increases after TP only in rank 4 animals, indicating a reinforcing effect of TP on the behavior. Corticosterone and IFN-gamma production are higher and GcR binding capacity is lower in spring than in autumn, suggesting that seasonal fluctuations in the immune system may be related to the pattern of secretion of immunomodulatory hormones. In autumn, corticosterone decreases after TP treatment and increases after social interaction, while GcR binding capacity decreases after TP treatment and social interaction. IFN-gamma production decreases in spring and increases in autumn after TP treatment plus social interaction, indicating that the modulating action of testosterone is related to the current immune status. The relationship between dominance, testosterone and the immune system in spring is suggested by the finding that GcR binding capacity after TP treatment is directly related to social rank, as confirmed by the positive correlation with dominance behavior frequency. The dominance index is positively correlated with GcR binding capacity and negatively with IFN-gamma production before TP treatment, indicating that high receptor activity in immunocompetent cells and low immunoreactivity could be prerequisites for dominance behavior. The immunosuppressive effect of corticosterone and the mechanism of down-regulation on GcR are confirmed by the negative correlations with IFN-gamma production and GcR binding capacity.     

Ageing and telomeres: a study into organ- and gender-specific telomere shortening

Telomeres, the non-coding sequences at the ends of chromosomes, in the absence of telomerase, progressively shorten with each cell division. Shortening of telomeres can induce cell cycle arrest and apoptosis. The aim of this study was to investigate age- and gender-related changes in telomere length in the rat and to detect possible tissue- specific rates of telomere shortening. Changes with age in telomere lengths were assessed by Southern blotting in the kidney, pancreas, liver, lung and brain of male and female rats. We determined the percentage of telomeres in various molecular size regions rather than measuring the average telomere length. The latter was unable to detect telomere shortening in the tissues. The percentage of short telomeres increased with age in the kidney, liver, pancreas and lung of both males and females, but not in the brain. Males had shorter telomeres than females in all organs analysed except the brain, where the lengths were similar. These findings indicate that telomeres shorten in the rat kidney, liver, pancreas and the lung in an age-dependent manner. These data also provide a novel mechanism for the gender-related differences in lifespan and suggest a tissue-specific regulation of telomere length during development and ageing in the rat.     

Mother-to-child transmission of HIV in Botswana: an ethical perspective on mandatory testing

Mother-to-child transmission (MTCT) of HIV represents a particularly dramatic aspect of the HIV epidemic with an estimated 600,000 newborns infected yearly, 90% of them living in sub-Saharan Africa. Since the beginning of the HIV epidemic, an estimated 5.1 million children worldwide have been infected with HIV. MTCT is responsible for 90% of these infections. Two-thirds of the MTCT are believed to occur during pregnancy and delivery, and about one-third through breastfeeding. As the number of women of child bearing age infected with HIV rises, so does the number of infected children. It is apparent that voluntary testing in Botswana has made some valuable inroads in decreasing perinatal HIV transmission, but the statistics showing the increased rate of HIV infection among women 15-24 years of age are not very promising. After reviewing all the pertinent scientific data it is clear that mandatory HIV testing of all pregnant women in conjunction with the implementation of a full package of interventions would save thousands of lives -- mothers, newborns and others who could be infected as a result of these women not being aware of their HIV status. If the protection and preservation of human life is a priority in Botswana, then it is time to allow for mandatory HIV testing of all pregnant women, before it is too late for those who are the most vulnerable. To do less would be medically inappropriate and ethically irresponsible.     

The lipidomic correlates of epigenetic aging across the adult lifespan: A population-based study

Lipid signaling is involved in longevity regulation, but which specific lipid molecular species affect human biological aging remains largely unknown. We investigated the relation between complex lipids and DNA methylation-based metrics of biological aging among 4181 participants (mean age 55.1 years (range 30.0–95.0)) from the Rhineland Study, an ongoing population-based cohort study in Bonn, Germany. The absolute concentration of 14 lipid classes, covering 964 molecular species and 267 fatty acid composites, was measured by Metabolon Complex Lipid Panel. DNA methylation-based metrics of biological aging (AgeAccelPheno and AgeAccelGrim) were calculated based on published algorithms. Epigenome-wide association analyses (EWAS) of biological aging-associated lipids and pathway analysis were performed to gain biological insights into the mechanisms underlying the effects of lipidomics on biological aging. We found that higher levels of molecular species belonging to neutral lipids, phosphatidylethanolamines, phosphatidylinositols, and dihydroceramides were associated with faster biological aging, whereas higher levels of lysophosphatidylcholine, hexosylceramide, and lactosylceramide species were associated with slower biological aging. Ceramide, phosphatidylcholine, and lysophosphatidylethanolamine species with odd-numbered fatty acid tail lengths were associated with slower biological aging, whereas those with even-numbered chain lengths were associated with faster biological aging. EWAS combined with functional pathway analysis revealed several complex lipids associated with biological aging as important regulators of known longevity and aging-related pathways.     

Influence of socioeconomic status on survival of hepatocellular carcinoma in the Ontario population; a population-based study, 1990-2009

Background

Research has shown that people from higher socioeconomic status (SES) have better hepatocellular carcinoma (HCC) survival outcomes, although no such research has been carried out in Canada. We aimed to assess if an association between SES and HCC survival existed in the Canadian context.

Methodology/Prinicpal Findings

We conducted a population-based cohort study linking HCC cases identified in the Ontario Cancer Registry between 1990 and 2009 to administrative and hospital data. Logistic regression and chi-squared tests were used to evaluate associations between SES (income quintile) and covariates. The Kaplan-Meier method was used to estimate survival. Sequential analysis of the proportional-hazards models were used to determine the association between SES and HCC survival controlling for potential prognostic covariates. During the period 1990–2009, 5,481 cases of HCC were identified. A significant association was found between SES and curative treatment (p = 0.0003), but no association was found between SES and non-curative treatment (p = 0.064), palliative treatment (p = 0.680), or ultrasound screening (p = 0.615). The median survival for the lowest SES was 8.5 months, compared to 8.8 months for the highest SES group. The age- and sex-adjusted proportional-hazards model showed statistically significant difference in HCC survival among the SES groups, with hazard ratio 0.905 (95% confidence intervals 0.821, 0.998) when comparing highest to lowest SES group. Further adjustments indicated that potentially curative treatment was the likely explanation for the association between SES and HCC survival.

Conclusions/Significance

Our findings suggest that a 10% HCC survival advantage exists for the higher SES groups. This association between SES and HCC survival is most likely a reflection of lack of access to care for low SES groups, revealing inequities in the Canadian healthcare system.     

HIV evolution in response to HLA-restricted CTL selection pressures: a population-based perspective

Cytotoxic T lymphocytes (CTL) recognize antigenic peptides displayed by HLA class I molecules on the infected cell surface and represent a major selective force driving HIV evolution through a phenomenon known as "immune escape". Here we summarize recent advances in our understanding of the consequences of CTL escape on HIV evolution at the population level and discuss its implications for HIV vaccine design.     

Interaction between HIV awareness, knowledge, safe sex practice and HIV prevalence: evidence from Botswana

This paper makes methodological and empirical contributions to the study of HIV in the context of Botswana, a country with high HIV prevalence. Comparable evidence is presented from India to put the Botswana results in perspective. The results point to the strong role played by affluence and education in increasing HIV knowledge, promoting safe sex and reducing HIV prevalence. The study presents African evidence on the role played by the empowerment of women in promoting safe sex practices such as condom use. The lack of significant association between HIV prevalence and safe sex practice points to the danger of HIV-infected individuals spreading the disease through multiple sex partners and unprotected sex. This danger is underlined by the finding that females with multiple sex partners are at higher risk of being infected with HIV. These results take on special policy significance in the context of Botswana, where the issue of multiple sex partners has not been adequately addressed in the programme to contain the spread of HIV.