Sequence analysis of human immunodeficiency virus type 1: A cross-sectional and longitudinal analysis

The replication of HIV-1 and the turnover of CD4 cells in vivo is a highly dynamic process. This environment of continuous de novo virus infection and extensive replication provides an ideal setting for the generation of HIV-1 variants. The objectives of this thesis were to perform a cross-sectional and longitudinal sequence analysis of HIV-1 in blood and multiple tissues of HIV-1 infected individuals. Five to 20 clones of Polymerase Chain Reaction (PCR) amplicons were sequenced and their relationships investigated using phylogenetic methods. An analysis of V3 sequences from a patient at the time of seroconversion revealed a homogeneous quasispecies which contrasted with the high diversity observed in the V3 quasispecies from a patient with AIDS. Phylogenetic analysis of HIV-LTR variants from LN and blood from 4 patients revealed 2 distinct patterns. First, an independent clustering of LN and PBMC variants, indicating a compartmentalisation of the two quasispecies for the patient with an intact lymph node. Second, non-polarised trees with variants from either LN or PBMC present in common branches for the patients with a disrupted LN architecture. These results suggest that the lymph nodes may be important in the sequestration/evolution of distinct HIV-1 variants. A similar phylogenetic analysis has been carried out on LTR variants from multiple postmortem samples (spleen, lung, spinal cord, ganglion, lymph node and blood) of a patient who died with AIDS. The results revealed a genetically distinct LTR quasispecies in the nervous tissues compared to that present in the other tissues. The nervous tissue quasispecies was characterised by 7 mutations in the normally conserved TAR region which would be expected to abrogate tat transactivation. However, this quasispecies showed the maintenance of prototypic NF-kB sites which would allow TAR independent kB tat transactivation to occur. These data provide evidence for a role of the LTR in the adaptation of HIV-1 to the nervous tissue environment by optimising the use of specific cellular transcription factor(s)

Adapting the DOTS Framework for Tuberculosis Control to the Management of Non-Communicable Diseases in Sub-Saharan Africa

Anthony Harries and colleagues discuss how the DOTS paradigm could be adapted for controlling diseases such as diabetes in resource-poor countries

Which population level environmental factors are associated with asthma, rhinoconjunctivitis and eczema? Review of the ecological analyses of ISAAC Phase One.

The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One showed large worldwide variations in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema, up to 10 to 20 fold between countries. Ecological analyses were undertaken with ISAAC Phase One data to explore factors that may have contributed to these variations, and are summarised and reviewed here.In ISAAC Phase One the prevalence of symptoms in the past 12 months of asthma, rhinoconjunctivitis and eczema were estimated from studies in 463,801 children aged 13 - 14 years in 155 centres in 56 countries, and in 257,800 children aged 6-7 years in 91 centres in 38 countries. Ecological analyses were undertaken between symptom prevalence and the following: Gross National Product per capita (GNP), food intake, immunisation rates, tuberculosis notifications, climatic factors, tobacco consumption, pollen, antibiotic sales, paracetamol sales, and outdoor air pollution.Symptom prevalence of all three conditions was positively associated with GNP, trans fatty acids, paracetamol, and women smoking, and inversely associated with food of plant origin, pollen, immunisations, tuberculosis notifications, air pollution, and men smoking. The magnitude of these associations was small, but consistent in direction between conditions. There were mixed associations of climate and antibiotic sales with symptom prevalence.The potential causality of these associations warrant further investigation. Factors which prevent the development of these conditions, or where there is an absence of a positive correlation at a population level may be as important from the policy viewpoint as a focus on the positive risk factors. Interventions based on small associations may have the potential for a large public health benefit

Asthma Prevalence, Knowledge, and Perceptions among Secondary School Pupils in Rural and Urban Costal Districts in Tanzania.

Asthma is a common chronic disease of childhood that is associated with significant morbidity and mortality. We aimed to estimate the prevalence of asthma among secondary school pupils in urban and rural areas of coast districts of Tanzania. The study also aimed to describe pupils' perception towards asthma, and to assess their knowledge on symptoms, triggers, and treatment of asthma. A total of 610 pupils from Ilala district and 619 pupils from Bagamoyo district formed the urban and rural groups, respectively. Using a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, a history of "diagnosed" asthma or the presence of a wheeze in the previous 12 months was obtained from all the studied pupils, along with documentation of their perceptions regarding asthma. Pupils without asthma or wheeze in the prior 12 months were subsequently selected and underwent a free running exercise testing. A >= 20% decrease in the post-exercise Peak Expiratory Flow Rate (PEFR) values was the criterion for diagnosing exercise-induced asthma. The mean age of participants was 16.8 (+/-1.8) years. The prevalence of wheeze in the past 12 months was 12.1% in Bagamoyo district and 23.1% in Ilala district (p < 0.001). Self-reported asthma was found in 17.6% and 6.4% of pupils in Ilala and Bagamoyo districts, respectively (p < 0.001). The prevalence of exercise-induced asthma was 2.4% in Bagamoyo, and 26.3% in Ilala (P < 0.002). In both districts, most information on asthma came from parents, and there was variation in symptoms and triggers of asthma reported by the pupils. Non-asthmatic pupils feared sleeping, playing, and eating with their asthmatic peers. The prevalence rates of self-reported asthma, wheezing in the past 12 months, and exercise-induced asthma were significantly higher among urban than rural pupils. Although bronchial asthma is a common disease, pupils' perceptions about asthma were associated with fear of contact with their asthmatic peers in both rural and urban schools

Prevalence and classification of rhinitis in preschool children in Portugal: a nationwide study.

BACKGROUND: Information on rhinitis epidemiology in preschool children is scarce. OBJECTIVES: To estimate, in children with 3-5 years of age, current rhinitis prevalence, to describe rhinitis symptoms and associated sociodemographic characteristics, and to report allergic rhinitis and its impact on asthma (ARIA) classification. METHODS: Cross-sectional, nationwide, population-based study including children aged 3-5 years. A multistep selection strategy was used to obtain a representative sample. Data were collected at kindergartens and parish centers by face-to-face interview to caregivers, using an adapted ISAAC questionnaire. 'Current rhinitis' (CR) was defined as the presence of ≥1 rhinitis symptom (repeated sneezing and/or itchy nose, blocked nose for >1 h, or runny nose without having a cold/flu) in the last year. Rhinitis lasting ≥4 days/week and ≥4 consecutive weeks was classified as persistent. Moderate-severe disease interfered 'a moderate amount' or 'a lot' in daily activities. RESULTS: Five thousand and eighteen children were included. CR prevalence was 43.4% [95% CI (42.0-44.8%); n = 2179] and that of physician-diagnosed rhinitis was 11.7% [95% CI (10.8-12.6%); n = 588]. Of children with CR, 67% reported blocked nose, 48% rhinorrhea, and 46% sneezing/itchy nose. Considering ARIA classification, 30% of the population had mild intermittent, 3% mild persistent, 7% moderate-severe intermittent, and 3% moderate-severe persistent rhinitis. Children with CR had more current wheezing, physician-diagnosed asthma, self-reported food allergy, and family history of allergic disease. These characteristics were also associated with persistent and moderate-severe rhinitis. CONCLUSIONS: This is the first nationwide population-based study reporting rhinitis prevalence and ARIA classification in preschool children. In this age-group, rhinitis is frequent and underdiagnosed. About 25% children with rhinitis presented moderate-severe disease

A global framework for action to improve the primary care response to chronic non-communicable diseases: a solution to a neglected problem.

BACKGROUND: Although in developing countries the burden of morbidity and mortality due to infectious diseases has often overshadowed that due to chronic non-communicable diseases (NCDs), there is evidence now of a shift of attention to NCDs. DISCUSSION: Decreasing the chronic NCD burden requires a two-pronged approach: implementation of the multisectoral policies aimed at decreasing population-level risks for NCDs, and effective and affordable delivery of primary care interventions for patients with chronic NCDs. The primary care response to common NCDs is often unstructured and inadequate. We therefore propose a programmatic, standardized approach to the delivery of primary care interventions for patients with NCDs, with a focus on hypertension, diabetes mellitus, chronic airflow obstruction, and obesity. The benefits of this approach will extend to patients with related conditions, e.g. those with chronic kidney disease caused by hypertension or diabetes. This framework for a "public health approach" is informed by experience of scaling up interventions for chronic infectious diseases (tuberculosis and HIV). The lessons learned from progress in rolling out these interventions include the importance of gaining political commitment, developing a robust strategy, delivering standardised interventions, and ensuring rigorous monitoring and evaluation of progress towards defined targets. The goal of the framework is to reduce the burden of morbidity, disability and premature mortality related to NCDs through a primary care strategy which has three elements: 1) identify and address modifiable risk factors, 2) screen for common NCDs and 3) and diagnose, treat and follow-up patients with common NCDs using standard protocols. The proposed framework for NCDs borrows the same elements as those developed for tuberculosis control, comprising a goal, strategy and targets for NCD control, a package of interventions for quality care, key operations for national implementation of these interventions (political commitment, case-finding among people attending primary care services, standardised diagnostic and treatment protocols, regular drug supply, and systematic monitoring and evaluation), and indicators to measure progress towards increasing the impact of primary care interventions on chronic NCDs. The framework needs evaluation, then adaptation in different settings. SUMMARY: A framework for a programmatic "public health approach" has the potential to improve on the current unstructured approach to primary care of people with chronic NCDs. Research to establish the cost, value and feasibility of implementing the framework will pave the way for international support to extend the benefit of this approach to the millions of people worldwide with chronic NCDs

Current guidelines for the management of asthma in young children

The diagnosis and management of asthma in young children is difficult, since there are many different wheezy phenotypes with varying underlying aetiologies and outcomes. This review discusses the different approaches to managing young children with wheezy illnesses presented in recently published global guidelines. Four major guidelines published since 2007 are considered. Helpful approaches are presented to assist the clinician to decide whether a clinical diagnosis of asthma can, or should be made in a young child with a recurrent wheezy illness and which treatments would be appropriate, dependent on risk factors, age of presentation, response to initial treatment and safety considerations. Each of the guidelines provide useful information for clinicians assessing young children with recurrent wheezy illnesses. There are differences in classification of the disease and treatment protocols. Although a firm diagnosis of asthma may only be made retrospectively in some cases and there are several effective guidelines to initiating treatment. Consistent review of the need for ongoing treatment with a particular pharmacological modality is essential, since many children with recurrent wheezing in infancy go into spontaneous remission. It is probable that newer biomarkers of airway inflammation will assist the clinician as to when to initiate and when to continue pharmacological treatment in the future