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Febrile illness is a major burden in African children, and non-malarial causes of fever are uncertain. In this retrospective exploratory study, we used metagenomic next-generation sequencing (mNGS) to evaluate serum, nasopharyngeal, and stool specimens from 94 children (aged 2-54 months) with febrile illness admitted to Tororo District Hospital, Uganda. The most common microbes identified were Plasmodium falciparum (51.1% of samples) and parvovirus B19 (4.4%) from serum; human rhinoviruses A and C (40%), respiratory syncytial virus (10%), and human herpesvirus 5 (10%) from nasopharyngeal swabs; and rotavirus A (50% of those with diarrhea) from stool. We also report the near complete genome of a highly divergent orthobunyavirus, tentatively named Nyangole virus, identified from the serum of a child diagnosed with malaria and pneumonia, a Bwamba orthobunyavirus in the nasopharynx of a child with rash and sepsis, and the genomes of two novel human rhinovirus C species. In this retrospective exploratory study, mNGS identified multiple potential pathogens, including 3 new viral species, associated with fever in Ugandan children.

BackgroundIn high tuberculosis (TB) burden countries, a significant proportion of the latent TB reservoir is established by the age 5 years. There are critical knowledge gaps in our understanding of the age-specific prevalence of TB infection and the influence of HIV exposure on TB infection in the first 5 years of life among HIV-uninfected children in sub-Saharan Africa.MethodsWe measured TB infection with the Quantiferon Gold-in-Tube (QFT) and tuberculin skin tests (TST) in 447 children ≤60 months and their 284 HIV-infected and IV-uninfected mothers in rural Uganda.ResultsThe overall prevalence of TB infection in children ≤60 months by TST was 24% (95% confidence intervals [CI]: 19.9-27.9). The prevalence of TST positivity was highest among children in their first year of life (36%; 95% CI: 26.0-45.9) and declined with age to 19% at 36-60 months of age, χ test for trend P = 0.014. In contrast, 4% (95% CI: 1.9-5.87%) of children had a positive QFT, and there was no trend detected with age, P = 0.576. QFT positivity was detected as early as 5 months. HIV-exposed uninfected children had significantly higher odds of TB infection by QFT (odds ratio [OR]: 21.2; P = 0.008; 95% CI: 2.2-204.7) or positive TST or QFT (OR, 2.4; P = 0.020; 95% CI: 1.2-5.1) compared with HIV-unexposed uninfected children, adjusting for age, BCG vaccination and a positive maternal TST or QFT.ConclusionsAn appreciable prevalence of TB infection was detected in early childhood. HIV-exposed uninfected children have a higher risk for TB infection compared with children born to HIV-uninfected mothers.

Background: Long-lasting insecticidal nets (LLINs) are the primary malaria prevention tool, but their effectiveness is threatened by pyrethroid resistance. We embedded a pragmatic cluster-randomised trial into Uganda's national LLIN campaign to compare conventional LLINs with those containing piperonyl butoxide (PBO), a synergist that can partially restore pyrethroid susceptibility in mosquito vectors., Methods: 104 health sub-districts, from 48 districts in Uganda, were randomly assigned to LLINs with PBO (PermaNet 3.0 and Olyset Plus) and conventional LLINs (PermaNet 2.0 and Olyset Net) by proportionate randomisation using an iterative process. At baseline 6, 12, and 18 months after LLIN distribution, cross-sectional surveys were done in 50 randomly selected households per cluster (5200 per survey); a subset of ten households per cluster (1040 per survey) were randomly selected for entomological surveys. The primary outcome was parasite prevalence by microscopy in children aged 2-10 years, assessed in the as-treated population at 6, 12, and 18 months. This trial is registered with ISRCTN, ISRCTN17516395., Findings: LLINs were delivered to households from March 25, 2017, to March 18, 2018, 32 clusters were randomly assigned to PermaNet 3.0, 20 to Olyset Plus, 37 to PermaNet 2.0, and 15 to Olyset Net. In the as-treated analysis, three clusters were excluded because no dominant LLIN was received, and four clusters were reassigned, resulting in 49 PBO LLIN clusters (31 received PermaNet 3.0 and 18 received Olyset Plus) and 52 non-PBO LLIN clusters (39 received PermaNet 2.0 and 13 received Olyset Net). At 6 months, parasite prevalence was 11% (386/3614) in the PBO group compared with 15% (556/3844) in the non-PBO group (prevalence ratio [PR] adjusted for baseline values 0·74, 95% CI 0·62-0·87; p=0·0003). Parasite prevalence was similar at month 12 (11% vs 13%; PR 0·73, 95% CI 0·63-0·85; p=0·0001) and month 18 (12% vs 14%; PR 0·84, 95% CI 0·72-0·98; p=0·029)., Interpretation: In Uganda, where pyrethroid resistance is high, PBO LLINs reduced parasite prevalence more effectively than did conventional LLINs for up to 18 months. This study provides evidence needed to support WHO's final recommendation on use of PBO LLINs., Funding: The Against Malaria Foundation, UK Department for International Development, Innovative Vector Control Consortium, and Bill and Melinda Gates Foundation., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)