Publications

Gut microbiota bacterial depletions and altered metabolic activity at 3 months are implicated in childhood atopy and asthma. We hypothesized that compositionally distinct human neonatal gut microbiota (NGM) exist, and are differentially related to relative risk (RR) of childhood atopy and asthma. Using stool samples (n = 298; aged 1-11 months) from a US birth cohort and 16S rRNA sequencing, neonates (median age, 35 d) were divisible into three microbiota composition states (NGM1-3). Each incurred a substantially different RR for multisensitized atopy at age 2 years and doctor-diagnosed asthma at age 4 years. The highest risk group, labeled NGM3, showed lower relative abundance of certain bacteria (for example, Bifidobacterium, Akkermansia and Faecalibacterium), higher relative abundance of particular fungi (Candida and Rhodotorula) and a distinct fecal metabolome enriched for pro-inflammatory metabolites. Ex vivo culture of human adult peripheral T cells with sterile fecal water from NGM3 subjects increased the proportion of CD4 cells producing interleukin (IL)-4 and reduced the relative abundance of CD4CD25FOXP3 cells. 12,13-DiHOME, enriched in NGM3 versus lower-risk NGM states, recapitulated the effect of NGM3 fecal water on relative CD4CD25FOXP3 cell abundance. These findings suggest that neonatal gut microbiome dysbiosis might promote CD4 T cell dysfunction associated with childhood atopy.

OBJECTIVE

We sought to increase adolescent HIV testing across rural communities in east Africa and identify predictors of undiagnosed HIV.

DESIGN

Hybrid mobile testing.

METHODS

We enumerated 116 326 adolescents (10-24 years) in 32 communities of Uganda and Kenya (

SEARCH

NCT01864603): 98 694 (85%) reported stable (≥6 months of prior year) residence. In each community we performed hybrid testing: 2-week multidisease community health campaign that included HIV testing, followed by home-based testing of community health campaign nonparticipants. We measured adolescent HIV testing coverage and prevalence, and determined predictors of newly diagnosed HIV among HIV-infected adolescents using multivariable logistic regression.

RESULTS

A total of 86 421 (88%) stable adolescents tested for HIV; coverage was 86, 90, and 88% in early (10-14), mid (15-17), and late (18-24) adolescents, respectively. Self-reported prior testing was 9, 26, and 55% in early, mid, and late adolescents tested, respectively. HIV prevalence among adolescents tested was 1.6 and 0.6% in Ugandan women and men, and 7.1 and 1.5% in Kenyan women and men, respectively. Prevalence increased in mid-adolescence for women and late adolescence for men. Among HIV-infected adolescents, 58% reported newly diagnosed HIV. In multivariate analysis of HIV-infected adolescents, predictors of newly diagnosed HIV included male sex [odds ratio (OR) = 1.97 (95% confidence interval (CI): 1.42-2.73)], Ugandan residence [OR = 2.63 (95% CI: 2.08-3.31)], and single status [OR = 1.62 (95% CI: 1.23-2.14) vs. married)].

CONCLUSIONS

The SEARCH hybrid strategy tested 88% of stable adolescents for HIV, a substantial increase over the 28% reporting prior testing. The majority (57%) of HIV-infected adolescents were new diagnoses. Mobile HIV testing for adults should be leveraged to reach adolescents for HIV treatment and prevention.