Rationale: Recurrent wheeze and asthma are thought to result from alterations in early life immune development following respiratory syncytial virus (RSV) infection. However, prior studies of the nasal immune response to infection have assessed only individual cytokines, which does not capture the whole spectrum of response to infection. Objectives: To identify nasal immune phenotypes in response to RSV infection and their association with recurrent wheeze. Methods: A birth cohort of term healthy infants born June to December were recruited and followed to capture the first infant RSV infection. Nasal wash samples were collected during acute respiratory infection, viruses were identified by RT-PCR, and immune-response analytes were assayed using a multianalyte bead-based panel. Immune-response clusters were identified using machine learning, and association with recurrent wheeze at age 1 and 2 years was assessed using logistic regression. Measurements and Main Results: We identified two novel and distinct immune-response clusters to RSV and human rhinovirus. In RSV-infected infants, a nasal immune-response cluster characterized by lower non-IFN antiviral immune-response mediators, and higher type-2 and type-17 cytokines was significantly associated with first and second year recurrent wheeze. In comparison, we did not observe this in infants with human rhinovirus acute respiratory infection. Based on network analysis, type-2 and type-17 cytokines were central to the immune response to RSV, whereas growth factors and chemokines were central to the immune response to human rhinovirus. Conclusions: Distinct immune-response clusters during infant RSV infection and their association with risk of recurrent wheeze provide insights into the risk factors for and mechanisms of asthma development.

While undernutrition and infectious diseases are still persistent in developing countries, overweight, obesity, and associated comorbidities have become more prevalent. Uganda, a developing sub-Saharan African country, is currently experiencing the public health paradox of undernutrition and overnutrition. We utilized the 2011 Uganda Demographic and Health Survey (DHS) to examine risk factors and hot spots for underweight, overweight, and obesity among adult females (N = 2,420) and their children (N = 1,099) using ordinary least squares and multinomial logit regression and the ArcGIS Getis-Ord Gi* statistic. Overweight and obese women were significantly more likely to have overweight children, and overweight was correlated with being in the highest wealth class (OR = 2.94, 95% CI = 1.99–4.35), and residing in an urban (OR = 1.76, 95% CI = 1.34–2.29) but not a conflict prone (OR = 0.48, 95% CI = 0.29–0.78) area. Underweight clustered significantly in the Northern and Northeastern regions, while overweight females and children clustered in the Southeast. We demonstrate that the DHS can be used to assess geographic clustering and burden of disease, thereby allowing for targeted programs and policies. Further, we pinpoint specific regions and population groups in Uganda for targeted preventive measures and treatment to reduce the burden of overweight and chronic diseases in Uganda.

The potential for prenatal antibiotic exposure to influence asthma risk is not clear. We aimed to determine the effect of timing, dose, and spectrum of prenatal antibiotic exposure on the risk of childhood asthma. We conducted a population-based cohort study of 84 214 mother–child dyads to examine the association of prenatal antibiotic exposure and childhood asthma using multivariable logistic regression models. Sixty-four percent of pregnant women received antibiotics. Prenatal antibiotic exposure was associated dose-dependently with increased odds of childhood asthma (adjusted odds ratio [aOR] for interquartile increase of 2 courses [interquartile range, 0–2], 1.26 [95% confidence interval {CI}, 1.20–1.33]). Among children exposed to at least 1 course in utero, the effect of timing at the first course was moderated by total maternal courses. Among pregnant women receiving a single antibiotic course, timing of exposure had no effect on childhood asthma risk. Among women receiving > 1 course, early exposure of the first course was associated with greater childhood asthma risk. Compared to narrow spectrum–only antibiotic use, broad spectrum–only antibiotic exposure was associated with increased odds of asthma (aOR, 1.14 [95% CI, 1.05–1.24]). There were effect modifications (P < .001) by maternal asthma on total courses, and on timing of the first course, significant only among those without maternal asthma. Increased cumulative dose, early pregnancy first course, and broad-spectrum antibiotic exposure were associated with childhood asthma risk. Our study provides important evidence supporting judicious prenatal antibiotic use, particularly timing of use and choice of antibiotics, in preventing subsequent childhood asthma.