The Immunology of Asthma and Allergic Rhinitis

The immune system is a complex collection of cells, tissues, and chemical mediators positioned throughout the body, whose primary purpose is to protect us against infection. However, its function is not only fundamental in protection from infectious disease but also provides aberrant response in allergens such as with asthma and allergic rhinitis. Allergic diseases like asthma and allergic rhinitis are characterized by a distinct type of inflammatory response, driven by immunoglobulin E (IgE)-dependent mechanisms. In asthma and allergic rhinitis, the inflammatory response is mediated by interaction of several immune cells (monocytes, lymphocytes, and polymorphonuclear cells) and cellular chemical mediators. In particular, atopic allergic response leads to destruction of multiple target cells such as epithelial, parenchymal and vascular and connective tissue of the airways. In addition, in inflammatory response in asthma and allergic rhinitis, sensory nerves are sensitized, leading to clinical manifestations. Sneezing and coughing are hypersensitivity responses of sensory nerves in allergic rhinitis and asthma, respectively. Similarly, nasal congestion and discharge in allergic rhinitis are due to vasodilatation that leads to plasma exudates as well as mucous secretion. The allergic inflammatory response is regulated by several transcription factors, particularly nuclear factor-κb (NF-κB), GATA-3 protein 3, and GATA binding protein

A primer on immune responses and mechanisms

The immune response is how your body recognizes and defends itself against bacteria, viruses, and substances that appear foreign and harmful. Innate, or nonspecific, immunity is the defense system with which you were born. It protects you against all antigens. Innate immunity involves barriers that keep harmful materials from entering your body. An antigen-presenting cell (APC) is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using their T cell receptors (TCRs). APCs process antigens and present them to T-cells. They are found in a variety of tissue types. Professional antigen-presenting cells, including macrophages, B cells and dendritic cells, present foreign antigens to helper T cells, while virus-infected cells (or cancer cells) can present antigens originating inside the cell to cytotoxic T cells There are two broad classes of immune responses—antibody responses and cell-mediated immune responses, and they are carried out by different classes of lymphocytes, called B cells and T cells, respectively. The way the body defends itself against substances it sees as harmful or foreign. In an immune response, the immune system recognizes the antigens (usually proteins) on the surface of substances or microorganisms, such as bacteria or viruses, and attacks and destroys, or tries to destroy, them

Combination antiretroviral therapy in population affected by conflict: outcomes from large cohort in northern Uganda

Objective To measure the clinical and immunological outcomes of HIV positive adult patients receiving combination antiretroviral therapy in conflict affected northern Uganda

Prevalence of asthma among school children in Gaborone, Botswana.

Background: Asthma prevalence is high (>10%) in developed countries and although data is still missing for most of Africa, rates are increasing in developing regions as they become more westernized. We investigated the prevalence of asthma in school children in Gaborone, Botswana. Methods: This was a cross sectional descriptive study. ISAAC methodology was used. A representative proportionate size random sample of two age groups of children (13-14 year olds and 6-7 year olds) was consecutively enrolled from 10 schools. The schools were selected using a table of random numbers. A minimum sample size of 924 individuals (462 from each group) was adequate to achieve a precision of 3 % around our estimated prevalence of asthma of 10% with 95% confidence assuming a non-response rate of 20%. Data was collected using the validated International study of Asthma and Allergies in children (ISAAC) questionnaire. In accordance with the ISAAC criteria, Asthma was defined as wheezing in the previous 12 months. Data was captured in microsoft excel and analysed using SPSS version 23. Results: The prevalence of asthma (wheezing in the previous 12 months) was 16.5% (194/1175). Among the 6-7 year olds, the prevalence of asthma (wheezing in the previous 12 months) was 15.9%, while among the 13-14 years olds it was 16.8 %. The prevalence school type was 22.3 % in private schools versus 14.5 % in public schools. More severe asthma was associated with older children, 13 -14 years. The older children reported more limited speech due to wheezing (OR= 2.0, 95% CI =1.034, 3.9, p-value=0.043), ever had asthma (OR= 1.5, 95% CI=1.031, 2.3, p-value=0.034) and wheezing during exercise (OR=3.4, 95% CI= 2.5, 4.9, p-value= <0.001) compared to the younger children 6-7 years. Children from private schools had more wheezing symptoms. They were more likely to have ever wheezed (OR=2.2, .95% CI=1.7,2.9, p-value < 0.0001), wheezed in the previous twelve months (have asthma) (OR=1.7,95%CI=1.2,2.4, p-value = 0.001), ever had asthma (OR=2.4, 95% CI=1.7,3.5, pvalue< 0.0001), and wheezed during exercise (OR=1.8, 95% CI=1.4,2.4, p-value < 0.0001). Conclusion: The prevalence of asthma amongst school children in Gaborone, Botswana is high with older children experiencing more severe symptoms of asthma

Predictors of Poor CD4 and Weight Recovery in HIV-Infected Children Initiating ART in South Africa

Objective: To identify baseline demographic and clinical risk factors associated with poor CD4 and weight response after initiation of antiretroviral therapy (ART) in a cohort of human immunodeficiency virus (HIV)-infected children in KwaZulu-Natal, South Africa. Methods: We performed a retrospective cohort study of 674 children initiating antiretroviral therapy at McCord and St. Mary’s hospitals in KwaZulu-Natal, South Africa, from August 2003 to December 2008. We extracted data from paper charts and electronic medical records to assess risk factors associated with CD4 and weight response using logistic regression. Results: From the initial cohort of 901 children,10 years old initiating ART between August 2003 and December 2008, we analyzed 674 children with complete baseline data. Viral suppression rates (,400 copies/ml) were 84 % after six months of therapy and 88 % after 12 months of therapy. Seventy-three percent of children achieved CD4 recovery after six months and 89 % after 12 months. Weight-for-age Z-score (WAZ) improvements were seen in 58 % of children after six months of ART and 64 % after 12 months. After six months of ART, lower baseline hemoglobin (p = 0.037), presence of chronic diarrhea (p = 0.007), and virologic failure (p = 0.046) were all associated with poor CD4 recovery by multivariate logistic regression. After 12 months of ART, poor CD4 recovery was associated with higher baseline CD4 % (p = 0.005), chronic diarrhe

ShangRing versus Mogen clamp for early infant male circumcision in eastern sub-Saharan Africa: A multicentre, non-inferiority, adaptive, randomised controlled trial

Background: Use of medical devices represents a unique opportunity to facilitate scale-up of early infant male circumcision (EIMC) across sub-Saharan Africa. The ShangRing, a circumcision device prequalified by WHO, is approved for use in adults and adolescents and requires topical anaesthesia only. We aimed to investigate the safety and efficacy of the ShangRing versus the Mogen clamp for EIMC in infants across eastern sub-Saharan Africa. Methods: In this multicentre, non-inferiority, open-label, randomised controlled trial, we enrolled healthy male infants (aged Findings: Between Sept 17, 2018, and Dec 20, 2019, a total of 1420 infants were assessed for eligibility, of whom 1378 (97·0%) were enrolled. 689 (50·0%) infants were randomly assigned to undergo EIMC by ShangRing and 689 (50·0%) by Mogen clamp. 43 (6·2%) adverse events were observed in the ShangRing group and 61 (8·9%) in the Mogen clamp group (p=0·078). The most common treatment-related AE was intraoperative pain (Neonatal Infant Pain Scale score ≥5), with 19 (2·8%) events in the ShangRing and 23 (3·3%) in the Mogel clamp group. Rates of moderate and severe AEs were similar between both groups (29 [4·2%] in the ShangRing group vs 30 [4·4%] in the Mogen clamp group; difference –0·1%; one-sided 95% CI upper limit of 1·7%; p=0·89). No treatment-related deaths were reported. Interpretation: Use of the ShangRing device for EIMC showed safety, achieved high caregiver satisfaction, and did not differ from the Mogen clamp in other key measures. The ShangRing could be used by health systems and international organisations to further scale up EIMC across sub-Saharan Africa

Temporal Trends in the Characteristics of Children at Antiretroviral Therapy Initiation in Southern Africa: The IeDEA-SA Collaboration

BACKGROUND Since 2005, increasing numbers of children have started antiretroviral therapy (ART) in sub-Saharan Africa and, in recent years, WHO and country treatment guidelines have recommended ART initiation for all infants and very young children, and at higher CD4 thresholds for older children. We examined temporal changes in patient and regimen characteristics at ART start using data from 12 cohorts in 4 countries participating in the IeDEA-SA collaboration. METHODOLOGY/PRINCIPAL FINDINGS Data from 30,300 ART-naïve children aged <16 years at ART initiation who started therapy between 2005 and 2010 were analysed. We examined changes in median values for continuous variables using the Cuzick's test for trend over time. We also examined changes in the proportions of patients with particular disease severity characteristics (expressed as a binary variable e.g. WHO Stage III/IV vs I/II) using logistic regression. Between 2005 and 2010 the number of children starting ART each year increased and median age declined from 63 months (2006) to 56 months (2010). Both the proportion of children <1 year and ≥10 years of age increased from 12 to 19% and 18 to 22% respectively. Children had less severe disease at ART initiation in later years with significant declines in the percentage with severe immunosuppression (81 to 63%), WHO Stage III/IV disease (75 to 62%), severe anemia (12 to 7%) and weight-for-age z-score<-3 (31 to 28%). Similar results were seen when restricting to infants with significant declines in the proportion with severe immunodeficiency (98 to 82%) and Stage III/IV disease (81 to 63%). First-line regimen use followed country guidelines. CONCLUSIONS/SIGNIFICANCE Between 2005 and 2010 increasing numbers of children have initiated ART with a decline in disease severity at start of therapy. However, even in 2010, a substantial number of infants and children started ART with advanced disease. These results highlight the importance of efforts to improve access to HIV diagnostic testing and ART in children