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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]

Background. Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) is the state-of-the-art diagnostic for norovirus. Cycle threshold (Ct), an indicator of viral load, may be associated with symptomatic disease as well as demographic and outbreak characteristics. Methods. Data on (1) outbreak and sporadic cases and (2) asymptomatic controls in the United States and Latin America were analyzed. With multivariate regression models, we assessed relationships between various factors and Ct values, and we calculated odds ratios (ORs) for the presence of symptoms and attributable fractions of norovirus. Receiver-operating characteristic analysis was performed to define an optimal Ct cutoff to identify disease-causing infections. Results. Cycle threshold values were lower (ie, higher viral loads) among symptomatic cases (model-adjusted mean ± standard error: 25.3 ± 1.2) compared with asymptomatic controls (28.5 ± 1.4). Cycle threshold values were significantly different across age groups, norovirus genogroups, timing of specimen collection, outbreak settings, and transmission modes. Genogroup II (GII) Ct values were associated with presence of symptoms (OR = 1.1), allowing us to estimate that 16% of diarrheal disease was attributable to norovirus. The optimized Ct cutoff led to poor sensitivity and specificity for genogroup I and GII. Conclusions. Cycle threshold values were associated with host, pathogen, and outbreak factors. Cycle threshold values may not effectively distinguish disease-causing infection for individual patients, but they are useful for epidemiological studies aiming to attribute disease. [ABSTRACT FROM AUTHOR]

International environmental agreements (IEAs) offer a potent method for addressing environmental issues that transgress national borders, but realizing this capability has proven difficult in many cases. In the tradition of economic research in this field, the papers in this issue contribute to the elucidation of the barriers to and conditions for achieving effective agreements. This paper places the others in this issue in the context of the literature, employing a conceptual framework that captures the essential features of the processes necessary for effective collective action among countries, and highlights areas for further research. It is argued that more empirical research is required to complement the theoretical approach of much of the literature. Such research might not only assess the relevance of theoretical findings but also elucidate influences on the behaviour of country representatives such as pressures deriving from the values and attitudes of their constituencies. [ABSTRACT FROM AUTHOR]

Background: Many studies have documented lower vaccine efficacy among children in low-income countries, compared with their counterparts in high-income countries. This disparity is especially apparent with respect to oral vaccines such as rotavirus and oral polio vaccines. One potential contributing factor is the presence of maternal antenatal helminth infections, which can modulate the infant's developing immune system.Methods: Using a multiplex immunoassay, we tested plasma immunoglobulin A (IgA) or immunoglobulin G (IgG) levels specific for antigens in 9 routinely administered childhood vaccines among 1639 children aged approximately 13 months enrolled in the ECUAVIDA (Ecuador Life) birth cohort study in Ecuador. We compared vaccine responses in 712 children of mothers who tested positive for helminth infections in the last trimester of pregnancy to responses in 927 children of mothers without helminth infection.Results: Plasma IgA levels specific for antigens in rotavirus vaccine and oral polio vaccine containing poliovirus serotypes 1 and 3 were all significantly higher in children of helminth-infected mothers, compared with children of uninfected mothers. Plasma IgG levels specific for diphtheria, tetanus, pertussis, measles, rubella, and Haemophilus influenzae type b vaccine antigens were comparable between the 2 groups.Conclusions: Antenatal maternal helminth infections were not associated with reduced antibody responses to infant vaccines, but rather with modestly increased IgA responses to oral vaccines. [ABSTRACT FROM AUTHOR]

The ECUAVIDA birth cohort is studying the impact of exposures to soil-transmitted helminth (STH) parasites and early-life microbial exposures on the development of atopy, allergic diseases and immune responses in childhood. A total of 2404 newborns were recruited between 2006 and 2009 in a public hospital serving the rural district of Quininde, Esmeraldas Province, in a tropical region of coastal Ecuador. Detailed measurements were done around the time of the birth, at 7 and 13 months and at 2 and 3 years, and data collection is ongoing at 5 and 8 years. Data being collected include questionnaires for: sociodemographic, lifestyle, psychosocial (at 4-6 years only) and dietary (at 6-7 years only) factors; childhood morbidity and clinical outcomes; stool samples for parasites; blood samples for DNA, measurements of vaccine responses and other measures of immune function/inflammation; and anthropometrics. Allergen skin prick test reactivity is done from 2 years and measures of airway function and inflammation at 8 years. [ABSTRACT FROM AUTHOR]

Background. Although norovirus is the most common cause of gastroenteritis, there are few data on the community incidence of infection/disease or the patterns of acquired immunity or innate resistance to norovirus. Methods. We followed a community-based birth cohort of 194 children in Ecuador with the aim to estimate (1) the incidence of norovirus gastroenteritis from birth to age 3 years, (2) the protective effect of norovirus infection against subsequent infection/disease, and (3) the association of infection and disease with FUT2 secretor status. Results. Over the 3-year period, we detected a mean of 2.26 diarrheal episodes per child (range, 0-12 episodes). Norovirus was detected in 260 samples (18%) but was not found more frequently in diarrheal samples (79 of 438 [18%]), compared with diarrhea-free samples (181 of 1016 [18%]; P = .919). A total of 66% of children had at least 1 norovirus infection during the first 3 years of life, and 40% of children had 2 infections. Previous norovirus infections were not associated with the risk of subsequent infection. All genogroup II, genotype 4 (GII.4) infections were among secretor-positive children (P < .001), but higher rates of non-GII.4 infections were found in secretor-negative children (relative risk, 0.56; P = .029). Conclusions. GII.4 infections were uniquely detected in secretor-positive children, while non-GII.4 infections were more often found in secretor-negative children. [ABSTRACT FROM AUTHOR]

Ascaris lumbricoides infections in humans may have important effects on the development of allergy and on susceptibility to infectious diseases that start during early life. To investigate whether sensitization to A. lumbricoides occurs in utero, we measured interferon (IFN)-γ and interleukin (IL)-4 responses in A. lumbricoides antigen-stimulated cord blood from newborns of infected and noninfected mothers by flow cytometry. There was evidence of higher frequencies of IFN-γ-expressing and IL-4-expressing CD4+ T cells in newborns of infected mothers than in newborns of noninfected mothers. Our data provide evidence of in utero sensitization to A. lumbricoides and raise the possibility that the immunological effects of infection start in the fetus. [ABSTRACT FROM AUTHOR]

Geohelminth infections are associated with modulation of immunity to parasite antigens and aeroallergens. To investigate the possibility that this modulation is affected by anthelmintic treatment, we compared cytokine responses in children who were treated with repeated doses of albendazole over 1 year versus those in children who had were not treated. Wholeblood samples were cultured with Ascaris antigen and house dust mite and cockroach allergens, and levels of interleukin (IL)-5, IL-13, interferon-γ, and IL-10 were measured. Anthelmintic treatment was associated with enhanced production of Th2cytokines in response to parasite antigen but did not affect responses to aeroallergens. The data indicate that long-term treatment may be associated with increased Th2 antiparasite immunity. [ABSTRACT FROM AUTHOR]

Background. In areas where intestinal helminth infections are endemic, infections by these parasites may protect against skin test-measured reactivity to allergens, and it has been suggested that interleukin (IL)-10 may mediate this effect. This study investigated whether IL-10 and populations of IL-10+ T cells may modulate atopy in children living in an area where intestinal helminth infections are endemic. Methods. Ecuadorian schoolchildren from rural communities were assessed for skin test-measured reactivity to Periplaneta americana allergen and Dermatophagoides pteronyssinus allergen. Blood samples were collected from 39 skin test-positive and 41 skin test-negative children, and peripheral-blood leukocytes were cultured in the presence of Ascaris lumbricoides antigen, to measure IL-10 protein and the frequency of T cell populations expressing intracellular IL-10. We also investigated whether these immunological factors affected the association between allergen-specific IgE and skin test-measured reactivity to aeroallergens. Results. There was no evidence of association between the level of A. lumbricoides-induced IL-10 protein or IL-10+ T cells and skin test-measured reactivity to allergens. The association between allergen-specific IgE and skin test-measured reactivity was not affected by the level of IL-10 protein or the frequency of IL-10+ T cells. Conclusions. The results of this study do not support the notion that IL-10 plays a role in modulating atopy in children living in a tropical area where intestinal helminth infections are endemic. [ABSTRACT FROM AUTHOR]

Studies have shown a strong inverse relationship between atopy and geohelminth infection, indicating that atopy may protect against geohelminth infection. Resistance to ascariasis in atopic individuals may occur through greater immunoglobulin E-mediated responses and expression of T helper cell type 2 (Th2) cytokines to parasite antigens. To investigate the effect that atopy has on the immune response to Ascaris antigens, school-age children were recruited from rural schools in Ecuador. Immunologic variables were compared between children stratified by atopic and/or A. lumbricoides-infection status; the variables included cytokine expression by peripheral-blood mononuclear cells (PBMCs) and histamine release in response to Ascaris antigens. Atopic children had both greater frequencies of PBMCs expressing interleukin (IL)-4 and IL-5 and enhanced histamine release, compared with those in nonatopic children. Stratification by atopic and A. lumbricoides-infection status revealed the greatest histamine and Th2 cytokine responses in the stratum of atopic, noninfected children. Multivariate regression analyses showed significant effects for atopic status but not for infection status on Th2 cytokine expression and histamine release. [ABSTRACT FROM AUTHOR]

A well-tolerated single-day treatment regimen is required for the community-based treatment of pulmonary paragonimiasis. To identify an optimal single-day treatment regimen, an open clinical trial was performed to compare the efficacy of 2 single-day regimens of triclabendazole. From 1991 to 1993, a total of 154 Ecuadorian patients were allocated to receive either a single dose or 2 doses of 10 mg/kg triclabendazole. Treatment with both regimens was associated with a rapid parasitological response (determined by clearance of Paragonimus eggs from sputum), resolution of most clinical symptoms and radiological signs, and only mild adverse effects. At 3 months after treatment, the cure rate (clearance of eggs from sputum) was 90.9% in the 2-dose group and 84.4% in the single-dose group. Re-treatment with a second 2-dose regimen was curative in all remaining patients by 1 year of follow-up. Our findings show that both single-day treatment regimens of triclabendazole were highly effective in the treatment of pulmonary paragonimiasis and suggest that patients should be re-examined at 3 months to determine the need for repeat treatment. [Copyright &y& Elsevier]

To investigate the role of mast cells in treatment-associated adverse reactions in patients with onchocerciasis, changes in plasma tryptase levels and skin mast cell counts were examined in 2 groups of Onchocerca volvulus-infected subjects after ivermectin treatment. After treatment, an increase in tryptase levels was observed concurrent with the onset of blood eosinopenia and preceding the appearance of plasma eosinophil-derived neurotoxin (EDN) and interleukin-5. Tryptase levels were correlated with development of peripheral eosinopenia and markers of eosinophil activation and degranulation. Dermal mast cell numbers increased transiently at 24 h after treatment, preceding the onset of dermal eosinophil infiltration and the development of clinically apparent inflammation. Local reactions were strongly correlated with leveis of plasma tryptase and EDN, and the severity of systemic reactions was correlated with levels of tryptase, EDN, and interleukin-5. The data indicate that mast cells play a role in initiation of tissue inflammatory reactions after ivermectin treatment of onchocerciasis. [ABSTRACT FROM AUTHOR]

Presents information on a study which examined the association between Onchocerca volvulus infection and cellular immune responses. Types of cellular immune responsiveness; Methodology; Results and discussion.

Investigates the cytokine and antibody response to adult and larval stages of Ascaris lumbricoides in infected young adults living in an endemic area of Ecuador. Frequencies of peripheral blood mononuclear cells secreting interleukin (IL)-10, interferon-gamma, IL-4 and IL-5 in infected young adults; Levels of A. lumbricoides-specific antibodies in plasma from infected individuals.

Studies the vibriocidal antibody response to the oral cholera vaccine in children infected with Ascaris lumbricoides as well as the effect of albendazole pretreatment on the postvaccination response. Greater postvaccination rates of seroconversion in the treatment group that received albendazole; Greater rates of seroconversion and mean titer observed in the albendazole groupin subjects with non-O ABO blood groups.

Assesses the safety and biologic effects of recombinant human interleukin-10 in acute systemic inflammation using the antibiotic-induced Jarisch-Herxheimer reaction of Louse-borne relapsing fever. Pathogenesis of the systemic inflammatory response syndrome; Consequences associated with uncontrolled production of potent mediators; Onset of spirochete destruction.

Analyzes the role of eosinophil activation and sequestration in the development and severity of adverse reactions after treatment of Onchocerca volvulus infection with ivermectin. Decline in eosinophil counts in ivermectin-treated groups; Increase in the circulating levels of interleukin-5 and eosinophil-derived neurotoxin; Slin microfilarial densities before and after treatment.