Impact of tuberculosis on mortality among HIV-infected patients receiving antiretroviral therapy in Uganda: a prospective cohort analysis

Background

Tuberculosis (TB) disease affects survival among HIV co-infected patients on antiretroviral therapy (ART). Yet, the magnitude of TB disease on mortality is poorly understood.

Methods

Using a prospective cohort of 22,477 adult patients who initiated ART between August 2000 and June 2009 in Uganda, we assessed the effect of active pulmonary TB disease at the initiation of ART on all-cause mortality using a Cox proportional hazards model. Propensity score (PS) matching was used to control for potential confounding. Stratification and covariate adjustment for PS and not PS-based multivariable Cox models were also performed.

Results

A total of 1,609 (7.52%) patients had active pulmonary TB at the start of ART. TB patients had higher proportions of being male, suffering from AIDS-defining illnesses, having World Health Organization (WHO) disease stage III or IV, and having lower CD4 cell counts at baseline (p?<?0.001). The percentages of death during follow-up were 10.47% and 6.38% for patients with and without TB, respectively. The hazard ratio (HR) for mortality comparing TB to non-TB patients using 1,686 PS-matched pairs was 1.37 (95% confidence interval [CI]: 1.08 – 1.75), less marked than the crude estimate (HR?=?1.74, 95% CI: 1.49 – 2.04). The other PS-based methods and not PS-based multivariable Cox model produced similar results.

Conclusions

After controlling for important confounding variables, HIV patients who had TB at the initiation of ART in Uganda had an approximate 37% increased hazard of overall mortality relative to non-TB patients.

     

Understanding the role of tumor stem cells in glioblastoma multiforme: a review article

It has been hypothesized that cancer stem cells (CSC) may account for the pathogenesis underlying various tumors, including GBM. Markers of these CSCs can be potentially used as therapeutic targets. In this review, we discuss the most recent information regarding CSCs, their molecular biology and their potential role in GBM.     

A community based study of urogenital chlamydia trachomatis in males aged fifteen years and above,Dembia District,northwest Ethiopia

Chlamydia trachomatis is one of the most common causes of sexually transmitted diseases in sexually active males and females. Infertility is one of the serious complications of urogenital chlamydial infections. This study was carried out in Chuwahit town and the surrounding village, which is located southwest of Gondar town. The main objective was to estimate the prevalence of urogenital Chlamydia trachomatis among males aged fifteen years and above. The design used was a cross sectional survey. First catch urine was collected from males 15 years and above and interviews were made using a questionnaire. The urine samples were tested with an Enzyme Immuno-Assay (EIA), which is useful in rapid detection of chlamydia antigen. Among 199 males included in the study, thirty-three (16.6%) had laboratory evidence of urogenital Chlamydia trachomatis. The mean (SD) age of the study subjects was 29.3 (+/- 9) years. Students (8 out of 21, 38%) had the highest prevalence of urogenital Chlamydia compared to the other groups (OR = 4.10, 95% CI = 1.12, 14.48). The magnitude of urogenital chlamydia infection in males was high in the study area. Health professionals need to consider genital Chlamydial infections in the management and control of sexually transmitted diseases. Increasing the awareness of students towards urogenital Chlamydial trachomatis and teaching them about the benefits of using condoms is recommended.     

Hepatitis C virus envelope glycoproteins and potential for vaccine development

HCV envelope glycoproteins play an important role in the initiation of viral infection. The functional dichotomy of the individual HCV glycoproteins was investigated using VSV/HCV pseudotype virus. Surprisingly, VSV/HCV pseudotype virus generated from either E1 or E2 displayed infectivity of a number of mammalian cells. The use of pseudotyped virus has allowed us to better understand the similar and divergent properties of E1 and E2 glycoproteins decorating the envelope of HCV. The serum pseudotype virus neutralizing activity in patient sera did not exhibit a correlation with the infecting HCV genotype or virus load. HCV E2 glycoprotein induces a weak neutralizing antibody response, however the neutralization function was augmented by complement. Taken together, these observations suggest a role for both the glycoproteins in HCV attachment and entry into susceptible host cells. An understanding of HCV entry and strategies appropriate for mimicking cell surface molecules may help in the development of new therapeutic modalities against HCV infection. Furthermore, incorporation of the HCV glycoproteins in a candidate vaccine may offer protection, although additional work is necessary to enhance their immunogenicity.     

Helping northern Ethiopian communities reduce childhood mortality: population-based intervention trial

OBJECTIVE: More than 10 million children die each year mostly from preventable causes and particularly in developing countries. WHO guidelines for the Integrated Management of Childhood Illness (IMCI) are intended to reduce childhood mortality and are being implemented in Ethiopia. As well as specific clinical interventions, the role of the community in understanding and acting on childhood sickness is an important factor in improving survival. This trial sought to assess the effect on survival of community-based health promotion activities. METHODS: Two districts in northern Ethiopia were studied, each with a random sample of more than 4000 children less than 5 years old. Regular six-monthly visits were made to document deaths among children. After the first year, communities in one district were educated about issues of good childcare and caring for sick children while the other district received this information only after the trial ended. FINDINGS: Although overall mortality was higher in the post-intervention period, most of the increase was seen in the control area. A Cox proportional hazards model gave an adjusted hazard ratio of 0.66 (95% confidence interval = 0.46-0.95) for the intervention area compared with the control area in the post-intervention period, with no significant pre-intervention difference. Significant survival advantages were found for females, children of younger fathers, those with married parents, those living in larger households, and those whose nearest health facility was a health centre. For all of the children who died, only 44% of parents or caregivers had sought health care before the child's death. CONCLUSION: This non-specific community-based public health intervention, as an addition to IMCI strategies in local health facilities, appears to have significantly reduced childhood mortality in these communities. The possibility that such interventions may not effectively reach certain social groups (for example single parents) is an important consideration for implementation of similar strategies in future. The synergy between community awareness and the availability of effective peripheral health services is also an issue that needs further exploration.     

Multiorgan dysfunction in infants with post-asphyxial hypoxic-ischaemic encephalopathy

BACKGROUND: Multiorgan dysfunction (MOD) is one of four consensus based criteria for the diagnosis of intrapartum asphyxia. The theoretical concept behind MOD is the diving reflex (conservation of blood flow to vital organs at the cost of non-vital organs). OBJECTIVES: To assess the patterns of involvement of each major organ/system and combinations of involvement in infants with post-asphyxial hypoxic-ischaemic encephalopathy (HIE), and to describe this in relation to long term outcome. DESIGN: Retrospective cohort study. SETTING: Regional tertiary neonatal intensive care unit at the Hospital for Sick Children, Toronto, Canada. PATIENTS: Term neonates with post-intrapartal asphyxial HIE assessed for kidney, cardiovascular system, lung, and liver function. OUTCOME: Death and presence or absence of severe neurodevelopmental disability. RESULTS: Out of 130 of 144 eligible infants with outcome data, 80 (62%) had severe adverse outcome and 50 (38%) had good outcome. All infants had evidence of MOD (at least one organ dysfunction in addition to HIE). Renal, cardiovascular, pulmonary, and hepatic dysfunction was present in 58-88% of infants with good outcome and 64-86% of infants with adverse outcome. CONCLUSIONS: MOD was present in all the infants with severe post-asphyxial HIE. However, there was no association between MOD and outcome in these infants. No relation between individual or combinations of organ involvements and long term outcomes was observed.