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BACKGROUND: Recently, there has been an unexplained increase in the incidence of blackwater fever (BWF) in Eastern Uganda. In this study, we evaluate the association between immune complexes, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and the occurrence and recurrence of BWF in children with severe malaria (SM). METHODS: Between 2014 and 2017, children aged six months to <4 years hospitalized with SM and community children (CC) were recruited at two hospitals in Central and Eastern Uganda. We measured serum circulating immune complexes (cIC) and their relationship to SM complications and post-discharge outcomes and evaluated effect mediation through G6PD deficiency. RESULTS: 557 children with SM and 101 CC were enrolled. The mean age of children was 2.1 years. Children with SM had higher cIC levels than CC, p<0.001. After controlling for age, sex, and site, cIC were associated with severe anemia, jaundice, and BWF (adjusted odds ratio, 95% confidence interval: 7.33 (3.45, 15.58), p<0.0001; 4.31 (1.68, 11.08), p=0.002; and 5.21 (2.06, 13.18), p<0.0001), respectively. cIC predicted readmissions for SM, severe anemia, and BWF (adjusted incidence rate ratios (95% confidence interval): 2.11 (1.33, 3.34), p=0.001; 8.62 (2.80, 26.59), p<0.0001; and 7.66 (2.62, 22.45), p<0.0001), respectively. The relationship was most evident in males where the frequency of the G6PD African allele (A-) was 16.8%. G6PD deficiency was associated with increases in cIC in males (p=0.01) and mediation analysis suggested G6PD deficiency contributes to recurrent severe anemia and BWF via increased cIC. CONCLUSIONS: Immune complexes are associated with hemolytic complications and predict recurrences in SM survivors.
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This cohort study examines clinical findings, medical treatment, and outcomes for infants in Indiana who were surrendered under Safe Haven laws.
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Niño Abandonado , Salud del Lactante , Humanos , Recién NacidoAsunto(s)
Tracto Gastrointestinal , Reacción en Cadena de la Polimerasa Multiplex , Niño , Heces , HumanosRESUMEN
INTRODUCTION: Adolescents living with HIV (ALHIV) may be vulnerable to widescale impacts of the COVID-19 pandemic and to health system responses which impact HIV care. We assessed healthcare worker (HCW) perspectives on impacts of the COVID-19 pandemic on adolescent HIV care delivery and engagement in western Kenya. METHODS: We performed in-depth qualitative interviews with HCW at 10 clinical sites in the Academic Model Providing Access to Healthcare in Kenya, from January to March, 2021. Semistructured interviews ascertained pandemic-related impacts on adolescent HIV care delivery and retention. RESULTS: Interviews were conducted with 22 HCWs from 10 clinics. HCWs observed adolescent financial hardships, unmet basic needs and school dropouts during the pandemic, with some adolescents relocating to rural homes, to partners or to the street. Marked increases in adolescent pregnancies and pregnancy complications were described, as well as barriers to family planning and antenatal care. Transportation challenges and restrictions limited access to care and prompted provision of multi-month refills, refills at local dispensaries or transfer to local facilities. Adolescent-friendly services were compromised, resulting in care challenges and disengagement from care. Clinic capacities to respond to adolescent needs were limited by funding cuts to multidisciplinary staff and resources. HCW and youth peer mentors (YPMs) demonstrated resilience, by adapting services, taking on expanded roles and leveraging available resources to support adolescent retention and access to care. CONCLUSIONS: ALHIV are uniquely vulnerable, and adolescent-friendly services are essential to their treatment. The combined effects of the pandemic, health system changes and funding cuts compromised adolescent-friendly care and limited capacity to respond to adolescent needs. There is a need to reinforce adolescent-friendly services within programmes and funding structures. Support for expanded YPM roles may facilitate dedicated, scalable and effective adolescent-friendly services, which are resilient and sustainable in times of crisis.
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COVID-19 , Infecciones por VIH , Adolescente , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/terapia , Personal de Salud , Humanos , Kenia/epidemiología , Pandemias , EmbarazoRESUMEN
In the adult mammalian CNS, chondroitin sulfate proteoglycans (CSPGs) and myelin-associated inhibitors (MAIs) stabilize neuronal structure and restrict compensatory sprouting following injury. The Nogo receptor family members NgR1 and NgR2 bind to MAIs and have been implicated in neuronal inhibition. We found that NgR1 and NgR3 bind with high affinity to the glycosaminoglycan moiety of proteoglycans and participate in CSPG inhibition in cultured neurons. Nogo receptor triple mutants (Ngr1(-/-); Ngr2(-/-); Ngr3(-/-); which are also known as Rtn4r, Rtn4rl2 and Rtn4rl1, respectively), but not single mutants, showed enhanced axonal regeneration following retro-orbital optic nerve crush injury. The combined loss of Ngr1 and Ngr3 (Ngr1(-/-); Ngr3(-/-)), but not Ngr1 and Ngr2 (Ngr1(-/-); Ngr2(-/-)), was sufficient to mimic the triple mutant regeneration phenotype. Regeneration in Ngr1(-/-); Ngr3(-/-) mice was further enhanced by simultaneous ablation of Rptpσ (also known as Ptprs), a known CSPG receptor. Collectively, our results identify NgR1 and NgR3 as CSPG receptors, suggest that there is functional redundancy among CSPG receptors, and provide evidence for shared mechanisms of MAI and CSPG inhibition.