T cell responses in repeated controlled human schistosome infection compared to natural exposure.

In Schistosoma-endemic regions a lack of natural sterilizing immunity means individuals are repeatedly infected, treated and reinfected. Due to difficulties in tracking natural infection, kinetics of host immune response during these reinfections have not been elucidated. Here, we use repeated (3x) controlled-human-Schistosoma mansoni infection (CHI) to study how antigen-specific T cells develop during reinfection (NCT05085470 study).

Global diversity of soil-transmitted helminths reveals population-biased genetic variation that impacts diagnostic targets.

Soil-transmitted helminths (STHs) are intestinal parasites that affect over a billion people worldwide. STH control relies on microscopy-based diagnostics to monitor parasite prevalence and enable post-treatment surveillance; however, molecular diagnostics are rapidly being developed due to increased sensitivity, particularly in low-STH-prevalence settings. The genetic diversity of helminths and its potential impact on molecular diagnostics remain unclear.

Exploring geographic differences in IgE response through network and manifold analyses.

Background: Component-resolved diagnostics allow detailed assessment of IgE sensitization to multiple allergenic molecules (component-specific IgEs, or c-sIgEs) and may be useful for asthma diagnosis. However, to effectively use component-resolved diagnostics across diverse settings, it is crucial to account for geographic differences.

Objective: We investigated spatial determinants of c-sIgE networks to facilitate development of diagnostic algorithms applicable globally.

Risk factors for atopic and non-atopic asthma in school-age children from high-income and low- and middle-income countries.

Background: It is well established that there are different asthma phenotypes, but whereas determinants of atopic asthma (AA) are well studied, little is known about non-atopic asthma (NAA). We compared risk factors for atopy, AA in atopics and NAA in non-atopics in children in a wide variety of countries.

Methods: Using four studies, across 23 countries, we assessed asthma status and atopy (skin prick tests) for children aged 6-17, plus risk factors from housing, heating, pets, family, diet and air quality categories.

Causes and MEchanisms foR non-atopic Asthma in Children (CAMERA) study: rationale and protocol.

Background: The Causes And MEchanisms foR non-atopic Asthma in children (CAMERA) study was designed to investigate risk factors and mechanisms of non-atopic asthma in children and young adults in Brazil, Ecuador, Uganda, and New Zealand. Initial epidemiological analyses using existing datasets identified and compared risk factors for both atopic and non-atopic asthma. The focus of this paper is the protocol for sample collection and analysis of clinical data on possible non-atopic mechanisms.

Gut microbiome signature and nasal lavage inflammatory markers in young people with asthma.

Background: Asthma is a complex disease and a severe global public health problem resulting from interactions between genetic background and environmental exposures. It has been suggested that gut microbiota may be related to asthma development; however, such relationships needs further investigation.

Objective: This study aimed to characterize the gut microbiota as well as the nasal lavage cytokine profile of asthmatic and nonasthmatic individuals.

Prevalence and correlates of neurocognitive impairment and psychiatric disorders among schoolchildren in Wakiso District, Uganda: a cross-sectional study.

There is limited data on the burden of mental disorders among children in the general population in Africa. We examined the prevalence and correlates of neurocognitive and psychiatric disorders among schoolchildren in Uganda. This cross-sectional study enrolled 322 schoolchildren aged 5-17years in Wakiso, Uganda.

Asthma inflammatory phenotypes on four continents: most asthma is non-eosinophilic.

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.

Infection-exposure in infancy is associated with reduced allergy-related disease in later childhood in a Ugandan cohort.

Background: Lack of early infection-exposure has been associated with increased allergy-related disease (ARD) susceptibility. In tropical Africa, little is known about which infections contribute to development of ARDs, and at which time.

Methods: We used latent class analysis to characterise the early infection-exposure of participants in a Ugandan birth cohort and assessed ARDs in later childhood.

Antibiotic Practices, Perceptions and Self-Medication Among Patients at a National Referral Hospital in Uganda.

Background: Antimicrobial resistance (AMR) is a major global health concern with increasing reports of microorganisms resistant to most of the available antibiotics. There are limited data on antibiotic practices, perceptions and self-medication among Ugandans, necessitating this study.

Methods: A cross-sectional study was conducted among patients at Kiruddu National Referral Hospital, Kampala, Uganda.

Anxiety disorders and asthma among adolescents in Uganda: role of early-life exposures.

The reasons for the positive association between anxiety disorders and asthma are unknown. We investigated the possible role of shared exposures in early life. We conducted a case-control study among adolescents (age 12-17 years) with and without asthma in urban Uganda, as part of a larger asthma case-control study.

Allergen skin test reactivity and asthma are inversely associated with ratios of IgG4/IgE and total IgE/allergen-specific IgE in Ugandan communities.

Background: Serum inhibition of allergen-specific IgE has been associated with competing IgG4 and non-specific polyclonal IgE. In allergen immunotherapy, beneficial responses have been associated with high IgG4/IgE ratios. Helminths potentiate antibody class switching to IgG4 and stimulate polyclonal IgE synthesis; therefore, we hypothesized a role for helminth-associated IgG4 and total IgE in protection against atopic sensitization and clinical allergy (asthma) in tropical low-income countries.

Risk factors associated with rhinitis, allergic conjunctivitis and eczema among schoolchildren in Uganda.

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.

Asthma control and management among schoolchildren in urban Uganda: results from a cross-sectional study.

: Children from low- and middle-income countries have poor asthma control, mainly because of poor management. The extent of this problem in Uganda is not well known, but such information would be useful to guide policy and practice. We therefore conducted a cross-sectional study among schoolchildren with asthma in urban Uganda, to assess the level of asthma control and management.

Cross-reactive carbohydrate determinant-specific IgE obscures true atopy and exhibits ⍺-1,3-fucose epitope-specific inverse associations with asthma.

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.

Risk factors for asthma among schoolchildren who participated in a case-control study in urban Uganda.

Data on asthma aetiology in Africa are scarce. We investigated the risk factors for asthma among schoolchildren (5-17 years) in urban Uganda. We conducted a case-control study, among 555 cases and 1115 controls.

Do helminth infections underpin urban-rural differences in risk factors for allergy-related outcomes?

Background: It is proposed that helminth exposure protects against allergy-related disease, by mechanisms that include disconnecting risk factors (such as atopy) from effector responses.

Objective: We aimed to assess how helminth exposure influences rural-urban differences in risk factors for allergy-related outcomes in tropical low- and middle-income countries.

Methods: In cross-sectional surveys in Ugandan rural Schistosoma mansoni (Sm)-endemic islands, and in nearby mainland urban communities with lower helminth exposure, we assessed risk factors for atopy (allergen-specific skin prick test [SPT] reactivity and IgE [asIgE] sensitization) and clinical allergy-related outcomes (wheeze, urticaria, rhinitis and visible flexural dermatitis), and effect modification by Sm exposure.

Parasites and allergy: Observations from Africa.

Population studies from the African continent have observed a marked increase in the prevalence of allergy-related diseases over the past few decades, but the cause of this rise is not fully understood. The most investigated potential risk factor has been the relationship between exposure to helminths and allergy-related outcomes. Immunologically, parallels exist between responses to helminths and to allergens as both are associated with elevated levels of immunoglobulin E, increased numbers of T helper 2 cells and other immune cells.

The Impact of Intensive Versus Standard Anthelminthic Treatment on Allergy-related Outcomes, Helminth Infection Intensity, and Helminth-related Morbidity in Lake Victoria Fishing Communities, Uganda: Results From the LaVIISWA Cluster-randomized Trial.

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.

Understanding asthma phenotypes: the World Asthma Phenotypes (WASP) international collaboration.

The World Asthma Phenotypes (WASP) study started in 2016 and has been conducted in five centres, in the UK, New Zealand, Brazil, Ecuador and Uganda. The objectives of this study are to combine detailed biomarker and clinical information in order to 1) better understand and characterise asthma phenotypes in high-income countries (HICs) and low and middle-income countries (LMICs), and in high and low prevalence centres; 2) compare phenotype characteristics, including clinical severity; 3) assess the risk factors for each phenotype; and 4) assess how the distribution of phenotypes differs between high prevalence and low prevalence centres. Here we present the rationale and protocol for the WASP study to enable other centres around the world to carry out similar analyses using a standardised protocol.

Effects of treating helminths during pregnancy and early childhood on risk of allergy-related outcomes: Follow-up of a randomized controlled trial.

Background: Helminth infections, common in low-income countries, may protect against allergy-related disease. Early exposure may be a key. In the Entebbe Mother and Baby Study, treating helminths during pregnancy resulted in increased eczema rates in early childhood.

A life without worms.

Worms have co-evolved with humans over millions of years. To survive, they manipulate host systems by modulating immune responses so that they cause (in the majority of hosts) relatively subtle harm. Anthelminthic treatment has been promoted as a measure for averting worm specific pathology and to mitigate subtle morbidities which may include effects on anaemia, growth, cognitive function and economic activity.

Life-course of atopy and allergy-related disease events in tropical sub-Saharan Africa: A birth cohort study.

Background: In high-income countries, allergy-related diseases (ARDs) follow a typical sequence, the 'Atopic March'. Little is known about the life-course of ARDs in the markedly different, low-income, tropical environment. We describe ARDs in a tropical, African birth cohort.

Maternal hookworm modifies risk factors for childhood eczema: results from a birth cohort in Uganda.

Background: Worms may protect against allergy. Early-life worm exposure may be critical, but this has not been fully investigated.

Objectives: To investigate whether worms in pregnancy and in early childhood are associated with childhood eczema incidence.

Helminth therapy or elimination: epidemiological, immunological, and clinical considerations.

Deworming is rightly advocated to prevent helminth-induced morbidity. Nevertheless, in affluent countries, the deliberate infection of patients with worms is being explored as a possible treatment for inflammatory diseases. Several clinical trials are currently registered, for example, to assess the safety or efficacy of Trichuris suis ova in allergies, inflammatory bowel diseases, multiple sclerosis, rheumatoid arthritis, psoriasis, and autism, and the Necator americanus larvae for allergic rhinitis, asthma, coeliac disease, and multiple sclerosis.