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Background: Most studies assessing pathophysiological heterogeneity in asthma have been conducted in high-income countries (HICs), with little known about the prevalence and characteristics of different asthma inflammatory phenotypes in low-and middle-income countries (LMICs). This study assessed sputum inflammatory phenotypes in five centres, in Brazil, Ecuador, Uganda, New Zealand (NZ) and the United Kingdom (UK).Methods: We conducted a cross-sectional study of 998 asthmatics and 356 non-asthmatics in 2016-20. All centres studied children and adolescents (age range 8-20 years), except the UK centre which involved 26-27 year-olds. Information was collected using questionnaires, clinical characterization, blood and induced sputum.Results: Of 623 asthmatics with sputum results, 39% (243) were classified as eosinophilic or mixed granulocytic, i.e. eosinophilic asthma (EA). Adjusted for age and sex, with NZ as baseline, the UK showed similar odds of EA (odds ratio 1.04, 95% confidence interval 0.37-2.94) with lower odds in the LMICs: Brazil (0.73, 0.42-1.27), Ecuador (0.40, 0.24-0.66) and Uganda (0.62, 0.37-1.04). Despite the low prevalence of neutrophilic asthma in most centres, sputum neutrophilia was increased in asthmatics and non-asthmatics in Uganda.Conclusions: This is the first time that sputum induction has been used to compare asthma inflammatory phenotypes in HICs and LMICs. Most cases were non-eosinophilic, including in settings where corticosteroid use was low. A lower prevalence of EA was observed in the LMICs than in the HICs. This has major implications for asthma prevention and management, and suggests that novel prevention strategies and therapies specifically targeting non-eosinophilic asthma are required globally. [ABSTRACT FROM AUTHOR]

A test was conducted to determine whether data from voluntary counseling and testing (VCT)/ prevention of mother-to-child transmission (PMTCT) programs can be used for HIV surveillance. There was a bias to accepting VCT in women with HIV, or risk factors for HIV infection, the former most apparent when there was low coverage.

Abstract Background Praziquantel treatment of schistosomiasis during pregnancy was only recommended in 2002; hence the effects of treatment during pregnancy are not fully known. We have therefore evaluated the effects on infection intensity and the immunological effects of praziquantel treatment against Schistosoma mansoni during pregnancy, compared with treatment after delivery. Methods A nested cohort of 387 Schistosoma mansoni infected women was recruited within a larger trial of de-worming during pregnancy. Women were randomised to receive praziquantel or placebo during pregnancy. All women were treated after delivery. Infection intensity after treatment was assessed by a single Kato-Katz examination of stool samples with duplicate slides and categorised as undetected, light (1–99 eggs per gram (epg)), moderate (100–399 epg) or heavy (≥400 epg). Antibodies against S. mansoni worm and egg antigens were measured by ELISA. Results were compared between women first treated during pregnancy and women first treated after delivery. Results At enrolment, 252 (65.1%) of the women had light infection (median (IQR) epg: 35 (11, 59)), 75 (19.3%) moderate (median (IQR) epg: 179(131, 227)) and 60 (15.5%) had heavy infection (median (IQR) epg: 749 (521, 1169)) with S. mansoni. At six weeks after praziquantel treatment during pregnancy S. mansoni infection was not detectable in 81.9% of the women and prevalence and intensity had decreased to 11.8% light, 4.7% moderate and 1.6% heavy a similar reduction when compared with those first treated after delivery (undetected (88.5%), light (10.6%), moderate (0.9%) and heavy (0%), p = 0.16). Parasite specific antibody levels were lower during pregnancy than after delivery. Praziquantel treatment during pregnancy boosted anti-worm IgG isotypes and to a lesser extent IgE, but these boosts were less pronounced than in women whose treatment was delayed until after delivery. Praziquantel had limited effects on antibodies against egg antigens. Conclusion S mansoni antigen-specific antibody levels and praziquantel-induced boosts in antibody levels were broadly suppressed during pregnancy, but this was not associated with major reduction in the efficacy of praziquantel. Long-term implications of these findings in relation to resistance to re-infection remain to be explored. Trial registration International Standard Randomised Controlled Trial Number for the current study: ISRCTN32849447 http://www.controlled-trials.com/ISRCTN32849447/elliott

Background: In high‐income, temperate countries, IgE to allergen extracts is a risk factor for, and mediator of, allergy‐related diseases (ARDs). In the tropics, positive IgE tests are also prevalent, but rarely associated with ARD. Instead, IgE responses to ubiquitous cross‐reactive carbohydrate determinants (CCDs) on plant, insect and parasite glycoproteins, rather than to established major allergens, are dominant. Because anti‐CCD IgE has limited clinical relevance, it may impact ARD phenotyping and assessment of contribution of atopy to ARD. Methods: Using an allergen extract‐based test, a glycan and an allergen (glyco)protein microarray, we mapped IgE fine specificity among Ugandan rural Schistosoma mansoni (Sm)‐endemic communities, proximate urban communities, and importantly in asthmatic and nonasthmatic schoolchildren. Results: Overall, IgE sensitization to extracts was highly prevalent (43%‐73%) but allergen arrays indicated that this was not attributable to established major allergenic components of the extracts (0%‐36%); instead, over 40% of all participants recognized CCD‐bearing components. Using glycan arrays, we dissected IgE responses to specific glycan moieties and found that reactivity to classical CCD epitopes (core β‐1,2‐xylose, α‐1,3‐fucose) was positively associated with sensitization to extracts, rural environment and Sm infection, but not with skin reactivity to extracts or sensitization to their major allergenic components. Interestingly, we discovered that reactivity to only a subset of core α‐1,3‐fucose‐carrying N‐glycans was inversely associated with asthma. Conclusions: CCD reactivity is not just an epiphenomenon of parasite exposure hampering specificity of allergy diagnostics; mechanistic studies should investigate whether specific CCD moieties identified here are implicated in the protective effect of certain environmental exposures against asthma. [ABSTRACT FROM AUTHOR]

Background: The prevalence of allergy‐related diseases (ARDs), including rhinitis, allergic conjunctivitis and eczema, is on the increase globally. The causes of this increase are not well established. Objectives: To investigate the risk factors associated with ARDs among schoolchildren in Uganda. Methods: We conducted a secondary data analysis of a large asthma case–control study involving 1700 schoolchildren, 5–17 years, in urban Uganda. ARDs were defined according to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Skin prick testing (SPT) was conducted using standard procedures and allergen‐specific IgE (asIgE) using ImmunoCAP®. We employed inverse probability weighted analysis to generate estimated prevalence data and weighted odds ratios. Results: The lifetime estimated weighted prevalence of reported rhinitis, allergic conjunctivitis and eczema was 43.3%, 39.5% and 13.5%; weighted prevalence in 12 months was 10.1%, 9.1% and 2.3%, respectively. There was overlap of ARDs, with 66.3% of 1193 schoolchildren who reported having ever an ARDs (including asthma) reporting two or more. Risk factors associated with reported rhinitis in the last 12 months were city residence at birth [adjusted odds ratio (95% confidence interval) 2.66 (1.42–4.99) compared to rural]; father's [2.62 (1.79–3.83)] and mother's history of allergic disease [2.12 (1.48–3.02)]; frequent de‐worming in the last 12 months [2.01 (1.30–3.11), ≥2 versus none]; current high frequency of 'trucks passing on the street near home' [2.59 (1.48–4.52), 'almost all the time' versus rarely] and positive SPT [1.54 (1.09–2.18)] but not asIgE [1.38 (0.60–3.15)]. The same pattern of risk factors was observed for allergic conjunctivitis and eczema. Conclusion: We found extensive multi‐morbidity of, and overlap in the risk factors for, rhinitis, conjunctivitis and eczema—similar to asthma risk factors—among schoolchildren in urban Uganda. This suggests a similar underlying cause for all ARDs, associated with exposure to urban lifestyles and environment in Uganda. [ABSTRACT FROM AUTHOR]

Background The prevalence of allergy-related diseases is increasing in low-income countries. Parasitic helminths, common in these settings, may be protective. We hypothesized that intensive, community-wide, anthelminthic mass drug administration (MDA) would increase allergy-related diseases, while reducing helminth-related morbidity. Methods In an open, cluster-randomized trial (ISRCTN47196031), we randomized 26 high-schistosomiasis-transmission fishing villages in Lake Victoria, Uganda, in a 1:1 ratio to receive community-wide intensive (quarterly single-dose praziquantel plus albendazole daily for 3 days) or standard (annual praziquantel plus 6 monthly single-dose albendazole) MDA. Primary outcomes were recent wheezing, skin prick test positivity (SPT), and allergen-specific immunoglobulin E (asIgE) after 3 years of intervention. Secondary outcomes included helminths, haemoglobin, and hepatosplenomegaly. Results The outcome survey comprised 3350 individuals. Intensive MDA had no effect on wheezing (risk ratio [RR] 1.11, 95% confidence interval [CI] 0.64–1.93), SPT (RR 1.10, 95% CI 0.85–1.42), or asIgE (RR 0.96, 95% CI 0.82–1.12). Intensive MDA reduced Schistosoma mansoni infection intensity: the prevalence from Kato Katz examinations of single stool samples from each patient was 23% versus 39% (RR 0.70, 95% CI 0.55–0.88), but the urine circulating cathodic antigen test remained positive in 85% participants in both trial arms. Hookworm prevalence was 8% versus 11% (RR 0.55, 95% CI 0.31–1.00). There were no differences in anemia or hepatospenomegaly between trial arms. Conclusions Despite reductions in S. mansoni intensity and hookworm prevalence, intensive MDA had no effect on atopy, allergy-related diseases, or helminth-related pathology. This could be due to sustained low-intensity infections; thus, a causal link between helminths and allergy outcomes cannot be discounted. Intensive community-based MDA has a limited impact in high-schistosomiasis-transmission fishing communities, in the absence of other interventions. Clinical Trials Registration ISRCTN47196031. [ABSTRACT FROM AUTHOR]