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Examining the relationship between diarrhea and linear growth in Kenyan HIV-exposed, uninfected infants.

ABSTRACT: BACKGROUND:Diarrhea in infancy can compromise linear growth and this relationship is likely influenced by diarrhea severity, number of episodes, and the timing of those episodes. HIV exposed, uninfected infants (HEU) have higher risk of growth faltering, infectious morbidity and mortality than HIV-unexposed infants and may be representative of children particularly vulnerable to diarrhea-associated linear growth faltering. METHODOLOGY/PRINCIPAL FINDINGS:We utilized data from a cohort of Kenyan HEU infants followed from birth to 12 months of age. Infant length and morbidity were ascertained at monthly study visits and sick visits. Longitudinal models estimated the association between diarrhea severity and length-for-age Z-score (LAZ) in the following month, at 12 months of age, and in 6-month intervals. The 372 enrolled infants experienced an average of 2.15 episodes (range: 0-8) of diarrhea and 0.54 episodes (0-4) of moderate-to-severe diarrhea (MSD) between birth and 12 months. Surviving infants had a mean LAZ of -0.97 (standard deviation: 1.2) at 12 months. MSD was significantly associated with an average loss of 0.14 (95% Confidence Interval [CI]: -0.24, -0.05, p = 0.003) in LAZ one month after the episode. Linear growth outcomes were not predicted by cumulative episodes of diarrhea, or timing of diarrhea during infancy. CONCLUSIONS/SIGNIFICANCE:Diarrhea severity influenced the relationship between diarrhea and subsequent linear growth. HEU infants with MSD may benefit from nutritional interventions following severe diarrhea to protect against linear growth faltering.

SUBMITTER: Deichsel EL

PROVIDER: S-EPMC7384652 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Examining the relationship between diarrhea and linear growth in Kenyan HIV-exposed, uninfected infants.

Deichsel Emily L EL John-Stewart Grace C GC Walson Judd L JL Mbori-Ngacha Dorothy D Richardson Barbra A BA Guthrie Brandon L BL Farquhar Carey C Bosire Rose R Pavlinac Patricia B PB

PloS one 20200727 7

<h4>Background</h4>Diarrhea in infancy can compromise linear growth and this relationship is likely influenced by diarrhea severity, number of episodes, and the timing of those episodes. HIV exposed, uninfected infants (HEU) have higher risk of growth faltering, infectious morbidity and mortality than HIV-unexposed infants and may be representative of children particularly vulnerable to diarrhea-associated linear growth faltering.<h4>Methodology/principal findings</h4>We utilized data from a coh ...[more]

PMID: 32716913

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Project description:ObjectivesHIV-exposed uninfected (HEU) infants have higher rates of severe and fatal infections compared with HIV-unexposed (HUU) infants, likely due to immune perturbations. We hypothesized that alterations in natural killer (NK) cell activity might occur in HEU infants and predispose them to severe infections.DesignCase-control study using cryopreserved peripheral blood mononuclear cells (PBMCs) at birth and 6 months from HEU infants enrolled from 2002 to 2009 and HUU infants enrolled from 2011 to 2013.MethodsNK cell phenotype and function were assessed by flow cytometry after 20-h incubation with and without K562 cells.ResultsThe proportion of NK cells among PBMCs was lower at birth in 12 HEU vs. 22 HUU (1.68 vs. 10.30%, p < 0.0001) and at 6 months in 52 HEU vs. 72 HUU (3.09 vs. 4.65%, p = 0.0005). At birth, HEU NK cells demonstrated increased killing of K562 target cells (p < 0.0001) and increased expression of CD107a (21.65 vs. 12.70%, p = 0.047), but these differences resolved by 6 months. Stimulated HEU NK cells produced less interferon (IFN)γ at birth (0.77 vs. 2.64%, p = 0.008) and at 6 months (4.12 vs. 8.39%, p = 0.001), and showed reduced perforin staining at 6 months (66.95 vs. 77.30%, p = 0.0008). Analysis of cell culture supernatants indicated that lower NK cell activity in HEU was associated with reduced interleukin (IL)-12, IL-15, and IL-18. Addition of recombinant human IL-12 to stimulated HEU PBMCs restored IFNγ production to that seen in stimulated HUU cultures.ConclusionNK cell proportion, phenotype, and function are altered in HEU infants. NK cell cytotoxicity and degranulation are increased in HEU at birth, but HEU NK cells have reduced IFNγ and perforin production, suggesting an adequate initial response, but decreased functional reserve. NK cell function improved with addition of exogenous IL-12, implicating impaired production of IL-12 by accessory cells. Alterations in NK cell and accessory cell function may contribute to the increased susceptibility to infection in HEU infants.

Dataset Information

Examining the relationship between diarrhea and linear growth in Kenyan HIV-exposed, uninfected infants.

Publications

Examining the relationship between diarrhea and linear growth in Kenyan HIV-exposed, uninfected infants.

Similar Datasets

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