Browsing by Author "Maitland, Kathryn"

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    Nasopharyngeal Microbiome Composition and its Clinical Correlates in Children Hospitalized with Severe Pneumonia in East Africa
    (Oxford University Press, 2026) Makori, O. Timothy; Gicheru, T. Elijah; Mburu, W. Maureen; Sada, S. Mercy; Nyawa, Omar; Mutunga, Martin; Lewa, Clement; Cheruiyot, Robinson; Kiguli, Sarah; Olupot-Olupot, Peter; Muhindo, Rita; Mogaka, Christabel; Williams, N. Thomas; Agoti, N. Charles; Maitland, Kathryn; Sande, J. Charles
    Background: Pneumonia remains the leading cause of infectious mortality in children under 5, with the highest burden in sub-Saharan Africa. Dysbiosis in nasopharyngeal (NP) microbiota may influence pneumonia susceptibility and progression, but little is known about its composition or clinical relevance in low- and middle-income countries. We characterized the NP microbiota of children hospitalized with severe pneumonia in East Africa and investigated associations with clinical outcomes. Methods: We performed 16S rRNA partial gene sequencing of NP swabs collected at hospital admission from 876 children enrolled in the COAST trial across 5 sites in Kenya and Uganda. Clinical, demographic, and virological data were prospectively collected. Microbial profiles were analyzed using hierarchical clustering, nonmetric multidimensional scaling, and multivariable regression to assess associations with respiratory viral infections, sepsis, cyanosis, bacteremia, coma, HIV status, malnutrition, sickle cell disease, malaria, and mortality. Results: The NP microbiome was structured in 6 distinct clusters, each dominated by different genera, including Staphylococcus, Streptococcus, Haemophilus, Dolosigranulum, Corynebacterium, and Moraxella. Multivariable models adjusting for study site and age showed a positive association between Corynebacterium and early mortality. Temporal analysis showed elevated Corynebacterium abundance in children who died within 48 hours of admission, then declined over longer 56 survival intervals, approaching levels observed in survivors. However, time-continuous models did not support this persistent association, suggesting a subgroup effect. Conclusions: We provide one of the largest high-resolution surveys of the pediatric upper airway microbiome in Africa, identifying microbial patterns associated with viral infection, HIV status, early death, and bacteremia. Keywords: 16 seconds rRNA sequencing; nasopharyngeal microbiome; pediatric pneumonia.
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    Plasma folate dynamics in Plasmodium falciparum-infected African children treated with artemisinin combination therapy and single low-dose primaquine or placebo
    (BMC, 2025) Ajayi, Seun; Onyamboko, A. Marie; Olupot-Olupot, Peter; Ayuen, S Dhol; Chimjinda, Natenapa; Taya, Chiraporn; Williams, N Thomas; Uyoga, Sophie; Maitland, Kathryn; Fanello, Caterina; Day, P J Nicholas; Mukaka, Mavuto; Taylor, R J Walter
    Background: Adding single low-dose (0.25 mg/kg) primaquine (SLDPQ) to block Plasmodium falciparum transmission is now a WHO recommendation. Whether SLDPQ increases haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd) patients, leading to increased folate demand and impaired haemoglobin (Hb) recovery is unknown. This study sought to answer this question. Methods: This randomized, placebo-controlled trial measured serial plasma folate concentrations [Day (D) 0, 3, 7 and 28] in falciparum-infected Ugandan and Congolese children (6 months to 11 years), treated with age-dosed SLDPQ/placebo and artemether-lumefantrine/dihydroartemisinin-piperaquine. Genotyping defined G6PD (G6PD c.202T allele) status. Multiple linear and non-linear, mixed effects, cubic spline regression were fitted to identify factors significantly associated with plasma folate at baseline and over time, respectively. Results: 408 children (3 had missing D0 values) had ≥ 1 plasma folate value. Of these, 66 (16.2%) were G6PD-deficient, 51 (12.5%) heterozygous females, 283 normal and 8 unknown. Mean baseline folate concentrations were 10.83 [standard deviation (SD) 3.58, SLDPQ] vs 10.92 (SD 4.54, placebo) ng/ml, associated independently with baseline Hb [estimate: 0.52 ng/ml (95% CI: 0.26 to 0.79, p = 0.0001)] and baseline parasitaemia [estimate: - 0.18 ng/ml (- 0.32 to - 0.05, p = 0.007)]. For all patients, mean plasma folate concentration paralleled mean haemoglobin concentration with an initial mean fall of 1.65 ng/ml (p < 0.0001 vs. baseline), followed by a sustained rise achieving a mean D28 concentration of 11.04 (SD 4.45) ng/ml. Over time, only age (p = 0.0001), male sex (p = 0.017) and baseline parasitaemia (p = 0.029) were significantly associated with a reduced plasma folate. Conclusion: SLDPQ and G6PD status did not compromise posttreatment plasma folate concentrations in young children with acute uncomplicated falciparum malaria, providing additional evidence of SLDPQ safety and supporting its use without G6PD testing. Trial registration: The trial is registered, reference number ISRCTN11594437. Keywords: Folate; Glucose-6-phosphate dehydrogenase; Malaria; Single low-dose primaquine