22 results on '"Prendergast, Andrew J."'
Search Results
2. The double burden of malnutrition in individuals: Identifying key challenges and re‐thinking research focus.
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Kiosia, Agklinta, Dagbasi, Aygul, Berkley, James A., Wilding, John P. H., Prendergast, Andrew J., Li, Jia V., Swann, Jon, Mathers, John C., Kerac, Marko, Morrison, Douglas, Drake, Lesley, Briend, Andre, Maitland, Kathryn, and Frost, Gary
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POLICY sciences ,MIDDLE-income countries ,MALNUTRITION ,SOCIAL determinants of health ,SOCIOECONOMIC factors ,GUT microbiome ,DIETARY fiber ,FOOD habits ,PUBLIC health ,FOOD supply ,METABOLOMICS ,OBESITY ,DIET ,LOW-income countries ,NUTRITION ,BIOMARKERS ,DIET therapy ,DISEASE risk factors - Abstract
The 'double burden of malnutrition' is a global health challenge that increasingly affects populations in both low‐ and middle‐income countries (LMICs). This phenomenon refers to the coexistence of undernutrition and overweight or obesity, as well as other diet‐related non‐communicable diseases, in the same population, household or even individual. While noteworthy progress has been made in reducing undernutrition in some parts of the world, in many of these areas, the prevalence of overweight and obesity is increasing, particularly in urban areas, resulting in greater numbers of people who were undernourished in childhood and have overweight or obesity in adulthood. This creates a complex and challenging situation for research experts and policymakers who must simultaneously address the public health burdens of undernutrition and overweight/obesity. This review identifies key challenges and limitations in the current research on the double burden of malnutrition in individuals, including the need for a more comprehensive and nuanced understanding of the drivers of malnutrition, the importance of context‐specific interventions and the need for greater attention to the food environment and food systems. We advocate for the re‐evaluation of research strategies and focus, with a greater emphasis on multidisciplinary and systems approaches and greater attention to the synergistic relationship between the biological, environmental, commercial and socio‐economic determinants of malnutrition. Addressing these key challenges can enable us to better comprehend and tackle the multifaceted and dynamic issues of the double burden of malnutrition, particularly in individuals and work towards more effective and sustainable solutions. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Inflammation: the driver of poor outcomes among children with severe acute malnutrition?
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Sturgeon, Jonathan P, Njunge, James M, Bourke, Claire D, Gonzales, Gerard Bryan, Robertson, Ruairi C, Bwakura-Dangarembizi, Mutsa, Berkley, James A, Kelly, Paul, and Prendergast, Andrew J
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INTESTINAL physiology ,MALNUTRITION treatment ,ENERGY metabolism ,MIDDLE-income countries ,INFLAMMATION ,IMMUNE system ,SEVERITY of illness index ,TREATMENT effectiveness ,SKIN physiology ,SEPSIS ,MALNUTRITION ,LOW-income countries ,WASTING syndrome ,NUTRITION disorders in children ,ENDOCRINE system ,DISEASE complications ,EVALUATION ,CHILDREN - Abstract
Severe acute malnutrition (SAM) is the most life-threatening form of undernutrition and underlies at least 10% of all deaths among children younger than 5 years in low-income countries. SAM is a complex, multisystem disease, with physiological perturbations observed in conjunction with the loss of lean mass, including structural and functional changes in many organ systems. Despite the high mortality burden, predominantly due to infections, the underlying pathogenic pathways remain poorly understood. Intestinal and systemic inflammation is heightened in children with SAM. Chronic inflammation and its consequent immunomodulation may explain the increased morbidity and mortality from infections in children with SAM, both during hospitalization and in the longer term after discharge. Recognition of the role of inflammation in SAM is critical in considering new therapeutic targets in this disease, which has not seen a transformational approach to treatment for several decades. This review highlights the central role of inflammation in the wide-ranging pathophysiology of SAM, as well as identifying potential interventions that have biological plausibility based on evidence from other inflammatory syndromes. [ABSTRACT FROM AUTHOR]
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- 2023
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4. Independent and combined effects of improved water, sanitation, and hygiene (WASH) and improved complementary feeding on early neurodevelopment among children born to HIV-negative mothers in rural Zimbabwe: Substudy of a cluster-randomized trial
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Gladstone, Melissa J., Chandna, Jaya, Kandawasvika, Gwendoline, Ntozini, Robert, Majo, Florence D., Tavengwa, Naume V., Mbuya, Mduduzi N. N., Mangwadu, Goldberg T., Chigumira, Ancikaria, Chasokela, Cynthia M., Moulton, Lawrence H., Stoltzfus, Rebecca J., Humphrey, Jean H., and Prendergast, Andrew J.
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Pediatric research ,Child development -- Research ,Hygiene -- Health aspects ,Rural water supply -- Health aspects -- Zimbabwe ,Poor children -- Health aspects -- Food and nutrition ,Medical personnel ,Glycosylated hemoglobin ,HIV ,Child care ,Health ,Pregnant women ,Child nutrition ,Grammar ,Poverty ,Nutrition ,Handwashing ,Hemoglobins ,Workers ,Child health ,Children ,Biological sciences - Abstract
Background Globally, nearly 250 million children (43% of all children under 5 years of age) are at risk of compromised neurodevelopment due to poverty, stunting, and lack of stimulation. We tested the independent and combined effects of improved water, sanitation, and hygiene (WASH) and improved infant and young child feeding (IYCF) on early child development (ECD) among children enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe. Methods and findings SHINE was a cluster-randomized community-based 2x2 factorial trial. A total of 5,280 pregnant women were enrolled from 211 clusters (defined as the catchment area of 1-4 village health workers [VHWs] employed by the Zimbabwean Ministry of Health and Child Care). Clusters were randomly allocated to standard of care, IYCF (20 g of small-quantity lipid-based nutrient supplement per day from age 6 to 18 months plus complementary feeding counseling), WASH (ventilated improved pit latrine, handwashing stations, chlorine, liquid soap, and play yard), and WASH + IYCF. Primary outcomes were child length-for-age Z-score and hemoglobin concentration at 18 months of age. Children who completed the 18-month visit and turned 2 years (102-112 weeks) between March 1, 2016, and April 30, 2017, were eligible for the ECD substudy. We prespecified that primary inferences would be drawn from findings of children born to HIV-negative mothers; these results are presented in this paper. A total of 1,655 HIV-unexposed children (64% of those eligible) were recruited into the ECD substudy from 206 clusters and evaluated for ECD at 2 years of age using the Malawi Developmental Assessment Tool (MDAT) to assess gross motor, fine motor, language, and social skills; the MacArthur-Bates Communicative Development Inventories (CDI) to assess vocabulary and grammar; the A-not-B test to assess object permanence; and a self-control task. Outcomes were analyzed in the intention-to-treat population. For all ECD outcomes, there was not a statistical interaction between the IYCF and WASH interventions, so we estimated the effects of the interventions by comparing the 2 IYCF groups with the 2 non-IYCF groups and the 2 WASH groups with the 2 non-WASH groups. The mean (95% CI) total MDAT score was modestly higher in the IYCF groups compared to the non-IYCF groups in unadjusted analysis: 1.35 (0.24, 2.46; p = 0.017); this difference did not persist in adjusted analysis: 0.79 (-0.22, 1.68; p = 0.057). There was no evidence of impact of the IYCF intervention on the CDI, A-not-B, or self-control tests. Among children in the WASH groups compared to those in the non-WASH groups, mean scores were not different for the MDAT, A-not-B, or self-control tests; mean CDI score was not different in unadjusted analysis (0.99 [95% CI -1.18, 3.17]) but was higher in children in the WASH groups in adjusted analysis (1.81 [0.01, 3.61]). The main limitation of the study was the specific time window for substudy recruitment, meaning not all children from the main trial were enrolled. Conclusions We found little evidence that the IYCF and WASH interventions implemented in SHINE caused clinically important improvements in child development at 2 years of age. Interventions that directly target neurodevelopment (e.g., early stimulation) or that more comprehensively address the multifactorial nature of neurodevelopment may be required to support healthy development of vulnerable children. Trial registration ClinicalTrials.gov NCT01824940, Author(s): Melissa J. Gladstone 1,*, Jaya Chandna 1,2, Gwendoline Kandawasvika 3, Robert Ntozini 2, Florence D. Majo 2, Naume V. Tavengwa 2, Mduduzi N. N. Mbuya 2,4, Goldberg T. Mangwadu [...]
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- 2019
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5. Microbial Translocation Does Not Drive Immune Activation in Ugandan Children Infected With HIV
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Fitzgerald, Felicity C, Lhomme, Edouard, Harris, Kathryn, Kenny, Julia, Doyle, Ronan, Kityo, Cissy, Shaw, Liam P, Abongomera, George, Musiime, Victor, Cook, Adrian, Brown, Julianne R, Brooks, Anthony, Owen-Powell, Ellen, Gibb, Diana M, Prendergast, Andrew J, Sarah Walker, A, Thiebaut, Rodolphe, Klein, Nigel, University College of London [London] (UCL), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Great Ormond Street Hospital for Children [London] (GOSH), Joint Clinical Research Centre, Queen Mary University of London (QMUL), This work was supported by the Medical Research Council (MRC, and grant MR/K023535/1 to F. F., grant MC_UU_12023/26 to the MRC Clinical Trials Unit at University College London [UCL], and support to CHAPAS-3), the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children National Health Service Foundation Trust (support to F. F.), UCL (support to F. F.), the Wellcome Trust (108065/Z/15/Z to A. J. P.), the European Developing Countries Clinical Trials Partnership (IP.2007.33011.006 to CHAPAS-3), the United Kingdom Department for International Development (support to CHAPAS-3), the Ministerio de Sanidady Consumo Spain (support to CHAPAS-3), and Cipla.
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DNA, Bacterial ,Male ,microbial translocation ,pediatrics ,HIV Infections ,DNA, Ribosomal ,immune activation ,Major Articles and Brief Reports ,children ,Humans ,Uganda ,Child ,Inflammation ,Africa ,HIV ,Infant ,sequencing ,Viral Load ,SISTM ,CD4 Lymphocyte Count ,Bacterial Translocation ,Child, Preschool ,HIV/AIDS ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Female ,Biomarkers - Abstract
Objective Immune activation is associated with morbidity and mortality during human immunodeficiency virus (HIV) infection, despite receipt of antiretroviral therapy (ART). We investigated whether microbial translocation drives immune activation in HIV-infected Ugandan children. Methods Nineteen markers of immune activation and inflammation were measured over 96 weeks in HIV-infected Ugandan children in the CHAPAS-3 Trial and HIV-uninfected age-matched controls. Microbial translocation was assessed using molecular techniques, including next-generation sequencing. Results Of 249 children included, 142 were infected with HIV; of these, 120 were ART naive, with a median age of 2.8 years (interquartile range [IQR], 1.7–4.0 years) and a median baseline CD4+ T-cell percentage of 20% (IQR, 14%–24%), and 22 were ART experienced, with a median age of 6.5 years (IQR, 5.9–9.2 years) and a median baseline CD4+ T-cell percentage of 35% (IQR, 31%–39%). The control group comprised 107 children without HIV infection. The median increase in the CD4+ T-cell percentage was 17 percentage points (IQR, 12–22 percentage points) at week 96 among ART-naive children, and the viral load was, We found no evidence of an association between microbial translocation and immune activation in Ugandan human immunodeficiency virus (HIV)–infected children over time during receipt of antiretroviral therapy or in comparison to HIV-uninfected controls. In this setting, other factors may be driving immune activation in both infected and uninfected children.
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- 2018
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6. Recovery of children following hospitalisation for complicated severe acute malnutrition.
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Bwakura‐Dangarembizi, Mutsa, Dumbura, Cherlynn, Amadi, Beatrice, Chasekwa, Bernard, Ngosa, Deophine, Majo, Florence D., Sturgeon, Jonathan P., Chandwe, Kanta, Kapoma, Chanda, Bourke, Claire D., Robertson, Ruairi C., Nathoo, Kusum J., Ntozini, Robert, Norris, Shane A., Kelly, Paul, and Prendergast, Andrew J.
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MALNUTRITION treatment ,STATURE ,HIV infections ,CONFIDENCE intervals ,NUTRITIONAL assessment ,CONVALESCENCE ,ANTHROPOMETRY ,PATIENT readmissions ,REGRESSION analysis ,FISHER exact test ,MANN Whitney U Test ,DISEASES ,TREATMENT effectiveness ,DESCRIPTIVE statistics ,CHI-squared test ,DATA analysis software ,CEREBRAL palsy ,HOSPITAL care of children ,SECONDARY analysis ,PROPORTIONAL hazards models ,EVALUATION ,CHILDREN - Abstract
Nutritional recovery and hospital readmission following inpatient management of complicated severe acute malnutrition (SAM) are poorly characterised. We aimed to ascertain patterns and factors associated with hospital readmission, nutritional recovery and morbidity, in children discharged from hospital following management of complicated SAM in Zambia and Zimbabwe over 52‐weeks posthospitalization. Multivariable Fine‐Gray subdistribution hazard models, with death and loss to follow‐up as competing risks, were used to identify factors associated with hospital readmission; negative binomial regression to assess time to hospitalisation and ordinal logistic regression to model factors associated with nutritional recovery. A total of 649 children (53% male, median age 18.2 months) were discharged to continue community nutritional rehabilitation. All‐cause hospital readmission was 15.4% (95% CI 12.7, 18.6) over 52 weeks. Independent risk factors for time to readmission were cerebral palsy (adjusted subhazard ratio (aSHR): 2.96, 95% CI 1.56, 5.61) and nonoedematous SAM (aSHR: 1.64, 95%CI 1.03, 2.64). Unit increases in height‐for‐age Z‐score (HAZ) (aSHR: 0.82, 95% CI 0.71, 0.95) and enrolment in Zambia (aSHR: 0.52, 95% CI 0.28, 0.97) were associated with reduced subhazard of time to readmission. Young age, SAM at discharge, nonoedematous SAM and cerebral palsy were associated with poor nutritional recovery throughout follow‐up. Collectively, nonoedematous SAM, ongoing SAM at discharge, cerebral palsy and low HAZ are independent risk factors for readmission and poor nutritional recovery following complicated SAM. Children with these high‐risk features should be prioritised for additional convalescent care to improve long‐term outcomes. Key messages: One‐in‐six children managed for SAM were readmitted into hospital over the first year after discharge and one‐in‐eight remained undernourished by 52 weeks of follow‐up.Nonoedematous SAM, ongoing SAM at the time of discharge and underlying cerebral palsy were independent risk factors for hospital readmission and poor nutritional recovery.Low HAZ was a risk factor for hospital readmission and poor nutritional recovery.Postdischarge care should focus on children with disability, nonoedematous SAM at initial hospitalisation and have ongoing SAM at the time of discharge.Stunting should be considered in the management of children with SAM. [ABSTRACT FROM AUTHOR]
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- 2022
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7. Linear growth trajectories in Zimbabwean infants12
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Gough, Ethan K, Moodie, Erica EM, Prendergast, Andrew J, Ntozini, Robert, Moulton, Lawrence H, Humphrey, Jean H, and Manges, Amee R
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Male ,Zimbabwe ,prenatal ,longitudinal ,Nutritional Status ,HIV Infections ,malnutrition ,Cohort Studies ,Child Development ,Nutritional Epidemiology and Public Health ,children ,Birth Weight ,Cluster Analysis ,Humans ,Longitudinal Studies ,Infant Nutritional Physiological Phenomena ,Vitamin A ,Growth Disorders ,infants ,stunting ,Infant ,Body Height ,Logistic Models ,Socioeconomic Factors ,Child, Preschool ,Female - Abstract
Background: Undernutrition in early life underlies 45% of child deaths globally. Stunting malnutrition (suboptimal linear growth) also has long-term negative effects on childhood development. Linear growth deficits accrue in the first 1000 d of life. Understanding the patterns and timing of linear growth faltering or recovery during this period is critical to inform interventions to improve infant nutritional status. Objective: We aimed to identify the pattern and determinants of linear growth trajectories from birth through 24 mo of age in a cohort of Zimbabwean infants. Design: We performed a secondary analysis of longitudinal data from a subset of 3338 HIV-unexposed infants in the Zimbabwe Vitamin A for Mothers and Babies trial. We used k-means clustering for longitudinal data to identify linear growth trajectories and multinomial logistic regression to identify covariates that were associated with each trajectory group. Results: For the entire population, the mean length-for-age z score declined from −0.6 to −1.4 between birth and 24 mo of age. Within the population, 4 growth patterns were identified that were each characterized by worsening linear growth restriction but varied in the timing and severity of growth declines. In our multivariable model, 1-U increments in maternal height and education and infant birth weight and length were associated with greater relative odds of membership in the least–growth restricted groups (A and B) and reduced odds of membership in the more–growth restricted groups (C and D). Male infant sex was associated with reduced odds of membership in groups A and B but with increased odds of membership in groups C and D. Conclusion: In this population, all children were experiencing growth restriction but differences in magnitude were influenced by maternal height and education and infant sex, birth weight, and birth length, which suggest that key determinants of linear growth may already be established by the time of birth. This trial was registered at clinicaltrials.gov as NCT00198718.
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- 2016
8. Head circumferences of children born to HIV-infected and HIV-uninfected mothers in Zimbabwe during the preantiretroviral therapy era
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Evans, Ceri, Chasekwa, Bernard, Ntozini, Robert, Humphrey, Jean H., and Prendergast, Andrew J.
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Male ,Zimbabwe ,Anthropometry ,Infant, Newborn ,HIV ,Infant ,HIV Infections ,Clinical Science: Concise Communication ,Child Development ,children ,Pregnancy ,Child, Preschool ,Africa ,head circumference ,Microcephaly ,Humans ,Female ,Longitudinal Studies ,Pregnancy Complications, Infectious ,Head ,Maternal-Fetal Exchange - Abstract
Objectives: To describe the head growth of children according to maternal and child HIV infection status. Design: Longitudinal analysis of head circumference data from 13 647 children followed from birth in the ZVITAMBO trial, undertaken in Harare, Zimbabwe, between 1997 and 2001, prior to availability of antiretroviral therapy (ART) or cotrimoxazole prophylaxis. Methods: Head circumference was measured at birth, then at regular intervals through 24 months of age. Mean head circumference-for-age Z-scores (HCZ) and prevalence of microcephaly (HCZ
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- 2016
9. Risk factors for postdischarge mortality following hospitalization for severe acute malnutrition in Zimbabwe and Zambia.
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Bwakura-Dangarembizi, Mutsa, Dumbura, Cherlynn, Amadi, Beatrice, Ngosa, Deophine, Majo, Florence D, Nathoo, Kusum J, Mwakamui, Simutanyi, Mutasa, Kuda, Chasekwa, Bernard, Ntozini, Robert, Kelly, Paul, Prendergast, Andrew J, and the HOPE-SAM study team
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MALNUTRITION treatment ,HOSPITALS ,STATISTICS ,CONFIDENCE intervals ,TIME ,MULTIVARIATE analysis ,HIV seroconversion ,ANTIRETROVIRAL agents ,SEVERITY of illness index ,RISK assessment ,DESCRIPTIVE statistics ,CEREBRAL palsy ,ACUTE diseases ,HOSPITAL care of children ,DISCHARGE planning ,CHILD mortality ,LONGITUDINAL method ,PROPORTIONAL hazards models ,EDEMA ,CHILDREN - Abstract
Background Children discharged from hospital following management of complicated severe acute malnutrition (SAM) have a high risk of mortality, especially HIV-positive children. Few studies have examined mortality in the antiretroviral therapy (ART) era. Objectives Our objectives were to ascertain 52-wk mortality in children discharged from hospital for management of complicated SAM, and to identify independent predictors of mortality. Methods A prospective cohort study was conducted in children enrolled from 3 hospitals in Zambia and Zimbabwe between July 2016 and March 2018. The primary outcome was mortality at 52 wk. Univariable and multivariable Cox regression models were used to identify independent risk factors for death, and to investigate whether HIV modifies these associations. Results Of 745 children, median age at enrolment was 17.4 mo (IQR: 12.8, 22.1 mo), 21.7% were HIV-positive, and 64.4% had edema. Seventy children (9.4%; 95% CI: 7.4, 11.7%) died and 26 exited during hospitalization; 649 were followed postdischarge. At discharge, 43.9% had ongoing SAM and only 50.8% of HIV-positive children were receiving ART. Vital status was ascertained for 604 (93.1%), of whom 55 (9.1%; 95% CI: 6.9, 11.7%) died at median 16.6 wk (IQR: 9.4, 21.9 wk). Overall, 20.0% (95% CI: 13.5, 27.9%) and 5.6% (95% CI: 3.8, 7.9%) of HIV-positive and HIV-negative children, respectively, died [adjusted hazard ratio (aHR): 3.83; 95% CI: 2.15, 6.82]. Additional independent risk factors for mortality were ongoing SAM (aHR: 2.28; 95% CI: 1.22, 4.25), cerebral palsy (aHR: 5.60; 95% CI: 2.72, 11.50) and nonedematous SAM (aHR: 2.23; 95% CI: 1.24, 4.01), with no evidence of interaction with HIV status. Conclusions HIV-positive children have an almost 4-fold higher mortality than HIV-negative children in the year following hospitalization for complicated SAM. A better understanding of causes of death, an improved continuum of care for HIV and SAM, and targeted interventions to improve convalescence are needed. [ABSTRACT FROM AUTHOR]
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- 2021
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10. Postdischarge interventions for children hospitalized with severe acute malnutrition: a systematic review and meta-analysis.
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Noble, Christie C A, Sturgeon, Jonathan P, Bwakura-Dangarembizi, Mutsa, Kelly, Paul, Amadi, Beatrice, and Prendergast, Andrew J
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MALNUTRITION treatment ,PATIENT aftercare ,META-analysis ,MEDICAL information storage & retrieval systems ,INFORMATION storage & retrieval systems ,MEDICAL databases ,SYSTEMATIC reviews ,HOSPITAL care ,MEDLINE ,CHILD mortality ,CHILDREN - Abstract
Background Children hospitalized with severe acute malnutrition (SAM) have poor long-term outcomes following discharge, with high rates of mortality, morbidity, and impaired neurodevelopment. There is currently minimal guidance on how to support children with SAM following discharge from inpatient treatment. Objectives This systematic review and meta-analysis aimed to examine whether postdischarge interventions can improve outcomes in children recovering from complicated SAM. Methods Systematic searches of 4 databases were undertaken to identify studies of interventions delivered completely or partially after hospital discharge in children aged 6–59 mo, following inpatient treatment of SAM. The main outcome of interest was mortality. Random-effects meta-analysis was undertaken where ≥2 studies were sufficiently similar in intervention and outcome. Results Ten studies fulfilled the inclusion criteria, recruiting 39–1781 participants in 7 countries between 1975 and 2015. Studies evaluated provision of zinc (2 studies), probiotics or synbiotics (2 studies), antibiotics (1 study), pancreatic enzymes (1 study), and psychosocial stimulation (4 studies). Six studies had unclear or high risk of bias in ≥2 domains. Compared with standard care, pancreatic enzyme supplementation reduced inpatient mortality (37.8% compared with 18.6%, P < 0.05). In meta-analysis there was some evidence that prebiotics or synbiotics reduced mortality (RR: 0.72; 95% CI: 0.51, 1.00; P = 0.049). Psychosocial stimulation reduced mortality in meta-analysis of the 2 trials reporting deaths (RR: 0.36; 95% CI: 0.15, 0.87), and improved neurodevelopmental scores in ≥1 domain in all studies. There was no evidence that zinc reduced mortality in the single study reporting deaths. Antibiotics reduced infectious morbidity but did not reduce mortality. Conclusions Several biological and psychosocial interventions show promise in improving outcomes in children following hospitalization for SAM and require further exploration in larger randomized mortality trials. This study was registered with PROSPERO as CRD42018111342 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=111342). [ABSTRACT FROM AUTHOR]
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- 2021
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11. Mortality, Human Immunodeficiency Virus (HIV) Transmission, and Growth in Children Exposed to HIV in Rural Zimbabwe.
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Evans, Ceri, Chasekwa, Bernard, Ntozini, Robert, Majo, Florence D, Mutasa, Kuda, Tavengwa, Naume, Mutasa, Batsirai, Mbuya, Mduduzi N N, Smith, Laura E, Stoltzfus, Rebecca J, Moulton, Lawrence H, Humphrey, Jean H, Prendergast, Andrew J, and Team, for the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) Trial
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HIV prevention ,HIV infection transmission ,ANTHROPOMETRY ,COMPARATIVE studies ,CONFIDENCE intervals ,GROWTH disorders ,HIV ,HIV infections ,HIV-positive persons ,HUMAN growth ,INFANT mortality ,MEDICAL screening ,MOTHERS ,RURAL conditions ,ANTIRETROVIRAL agents ,VERTICAL transmission (Communicable diseases) ,DESCRIPTIVE statistics ,CHILDREN ,FETUS - Abstract
Background Clinical outcomes of children who are human immunodeficiency virus (HIV)–exposed in sub-Saharan Africa remain uncertain. Methods The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial evaluated improved infant and young child feeding (IYCF) and/or improved water, sanitation, and hygiene in 2 rural Zimbabwean districts with 15% antenatal HIV prevalence and > 80% prevention of mother-to-child transmission (PMTCT) coverage. Children born between February 2013 and December 2015 had longitudinal HIV testing and anthropometry. We compared mortality and growth between children who were HIV-exposed and HIV-unexposed through 18 months. Children receiving IYCF were excluded from growth analyses. Results Fifty-one of 738 (7%) children who were HIV-exposed and 198 of 3989 (5%) children who were HIV-unexposed (CHU) died (hazard ratio, 1.41 [95% confidence interval {CI}, 1.02–1.93]). Twenty-five (3%) children who were HIV-exposed tested HIV positive, 596 (81%) were HIV-exposed uninfected (CHEU), and 117 (16%) had unknown HIV status by 18 months; overall transmission estimates were 4.3%–7.7%. Mean length-for-age z score at 18 months was 0.38 (95% CI,.24–.51) standard deviations lower among CHEU compared to CHU. Among 367 children exposed to HIV in non-IYCF arms, 147 (40%) were alive, HIV-free, and nonstunted at 18 months, compared to 1169 of 1956 (60%) CHU (absolute difference, 20% [95% CI, 15%–26%]). Conclusions In rural Zimbabwe, mortality remains 40% higher among children exposed to HIV, vertical transmission exceeds elimination targets, and half of CHEU are stunted. We propose the composite outcome of "alive, HIV free, and thriving" as the long-term goal of PMTCT programs. Clinical Trials Registration NCT01824940. [ABSTRACT FROM AUTHOR]
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- 2021
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12. Enhanced Prophylaxis plus Antiretroviral Therapy for Advanced HIV Infection in Africa
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Hakim, James, Musiime, Victor, Szubert, Alex J., Mallewa, Jane, Siika, Abraham, Agutu, Clara, Walker, Simon, Pett, Sarah L., Bwakura-Dangarembizi, Mutsa, Lugemwa, Abbas, Kaunda, Symon, Karoney, Mercy, Musoro, Godfrey, Kabahenda, Sheila, Nathoo, Kusum, Maitland, Kathryn, Griffiths, Anna, Thomason, Margaret J., Kityo, Cissy, Mugyenyi, Peter, Prendergast, Andrew J., Walker, A. Sarah, Gibb, Diana M., REALITY Trial Team, O'Hare, Bernadette Ann-Marie, DiFDMRCWellcome Trust, University of St Andrews. School of Medicine, and University of St Andrews. Infection and Global Health Division
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Male ,REALITY Trial Team ,0301 basic medicine ,Placebo-controlled study ,CHILDREN ,HIV Infections ,Kaplan-Meier Estimate ,law.invention ,DOUBLE-BLIND ,0302 clinical medicine ,Anti-Infective Agents ,Randomized controlled trial ,WORLDWIDE ,law ,Medicine ,030212 general & internal medicine ,Child ,11 Medical and Health Sciences ,Medicine(all) ,education.field_of_study ,Mortality rate ,Pyridoxine ,General Medicine ,Middle Aged ,OPEN-LABEL ,3. Good health ,Anti-Retroviral Agents ,Chemoprophylaxis ,Drug Therapy, Combination ,Female ,Life Sciences & Biomedicine ,medicine.drug ,Adult ,medicine.medical_specialty ,Tuberculosis ,Adolescent ,030106 microbiology ,Population ,NDAS ,R Medicine ,TUBERCULOSIS ,Article ,Young Adult ,03 medical and health sciences ,Medicine, General & Internal ,Pharmacotherapy ,SDG 3 - Good Health and Well-being ,PEOPLE ,General & Internal Medicine ,Internal medicine ,Trimethoprim, Sulfamethoxazole Drug Combination ,Isoniazid ,Humans ,Intensive care medicine ,education ,Africa South of the Sahara ,Aged ,Science & Technology ,AIDS-Related Opportunistic Infections ,business.industry ,MORTALITY ,ADULTS ,Raltegravir ,medicine.disease ,CD4 Lymphocyte Count ,HIV-1 ,business ,CRYPTOCOCCAL MENINGITIS - Abstract
Supported by the Joint Global Health Trials Scheme of the Medical Research Council (MRC), the U.K. Department for International Development, and the Wellcome Trust through a grant (G1100693),with additional support from the PENTA Foundation. The MRC Clinical Trials Unit at University College London is supported by grants from the MRC (MC-UU-12023/23 and MC-UU-12023/26). Dr. Prendergast is funded by a grant (108065/Z/15/Z) from the Wellcome Trust, which also funds the Malawi–Liverpool–Wellcome Trust Clinical Research Program at the University of Malawi College of Medicine through a grant (101113/Z/13/Z) and the Kenya Medical Research Institute (KEMRI)–Wellcome Trust Research Program through a grant (077092). Background: In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%. Methods: In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, we enrolled HIV-infected adults and children 5 years of age or older who had not received previous ART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter. They underwent simultaneous randomization to receive enhanced antimicrobial prophylaxis or standard prophylaxis, adjunctive raltegravir or no raltegravir, and supplementary food or no supplementary food. Here, we report on the effects of enhanced antimicrobial prophylaxis, which consisted of continuous trimethoprim-sulfamethoxazole plus at least 12 weeks of isoniazid-pyridoxine (coformulated with trimethoprim-sulfamethoxazole in a single fixed-dose combination tablet), 12 weeks of fluconazole, 5 days of azithromycin, and a single dose of albendazole, as compared with standard prophylaxis (trimethoprim-sulfamethoxazole alone). The primary end point was 24-week mortality. Results: A total of 1805 patients (1733 adults and 72 children or adolescents) underwent randomization to receive either enhanced prophylaxis (906 patients) or standard prophylaxis (899 patients) and were followed for 48 weeks (loss to follow-up, 3.1%). The median baseline CD4+ count was 37 cells per cubic millimeter, but 854 patients (47.3%) were asymptomatic or mildly symptomatic. In the Kaplan-Meier analysis at 24 weeks, the rate of death with enhanced prophylaxis was lower than that with standard prophylaxis (80 patients [8.9% vs. 108 [12.2%]; hazard ratio, 0.73; 95% confidence interval [CI], 0.55 to 0.98; P = 0.03); 98 patients (11.0%) and 127 (14.4%), respectively, had died by 48 weeks (hazard ratio, 0.76; 95% CI, 0.58 to 0.99; P = 0.04). Patients in the enhanced-prophylaxis group had significantly lower rates of tuberculosis (P = 0.02), cryptococcal infection (P = 0.01), oral or esophageal candidiasis (P = 0.02), death of unknown cause (P = 0.03), and new hospitalization (P = 0.03). However, there was no significant between-group difference in the rate of severe bacterial infection (P = 0.32). There were nonsignificantly lower rates of serious adverse events and grade 4 adverse events in the enhanced-prophylaxis group (P = 0.08 and P = 0.09, respectively). Rates of HIV viral suppression and adherence to ART were similar in the two groups. Conclusions: Among HIV-infected patients with advanced immunosuppression, enhanced antimicrobial prophylaxis combined with ART resulted in reduced rates of death at both 24 weeks and 48 weeks without compromising viral suppression or increasing toxic effects. Publisher PDF
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- 2017
13. Current Understanding of Innate Immune Cell Dysfunction in Childhood Undernutrition.
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Bourke, Claire D., Jones, Kelsey D. J., and Prendergast, Andrew J.
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MALNUTRITION ,CHILDREN ,MIDDLE-income countries ,CHILD death ,KNOWLEDGE gap theory - Abstract
Undernutrition affects millions of children in low- and middle-income countries (LMIC) and underlies almost half of all deaths among children under 5 years old. The growth deficits that characterize childhood undernutrition (stunting and wasting) result from simultaneous underlying defects in multiple physiological processes, and current treatment regimens do not completely normalize these pathways. Most deaths among undernourished children are due to infections, indicating that their anti-pathogen immune responses are impaired. Defects in the body's first-line-of-defense against pathogens, the innate immune system, is a plausible yet understudied pathway that could contribute to this increased infection risk. In this review, we discuss the evidence for innate immune cell dysfunction from cohort studies of childhood undernutrition in LMIC, highlighting knowledge gaps in almost all innate immune cell types. We supplement these gaps with insights from relevant experimental models and make recommendations for how human and animal studies could be improved. A better understanding of innate immune function could inform future tractable immune-targeted interventions for childhood undernutrition to reduce mortality and improve long-term health, growth and development. [ABSTRACT FROM AUTHOR]
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- 2019
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14. Microbial Translocation Does Not Drive Immune Activation in Ugandan Children Infected With HIV.
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Fitzgerald, Felicity C, Lhomme, Edouard, Harris, Kathryn, Kenny, Julia, Doyle, Ronan, Kityo, Cissy, Shaw, Liam P, Abongomera, George, Musiime, Victor, Cook, Adrian, Brown, Julianne R, Brooks, Anthony, Owen-Powell, Ellen, Gibb, Diana M, Prendergast, Andrew J, Sarah Walker, A, Thiebaut, Rodolphe, Klein, Nigel, and CHAPAS-3 Trial Team
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HIV-positive children ,ANTIRETROVIRAL agents ,NUCLEOTIDE sequencing ,ENTEROBACTERIACEAE ,T cells - Abstract
Objective: Immune activation is associated with morbidity and mortality during human immunodeficiency virus (HIV) infection, despite receipt of antiretroviral therapy (ART). We investigated whether microbial translocation drives immune activation in HIV-infected Ugandan children.Methods: Nineteen markers of immune activation and inflammation were measured over 96 weeks in HIV-infected Ugandan children in the CHAPAS-3 Trial and HIV-uninfected age-matched controls. Microbial translocation was assessed using molecular techniques, including next-generation sequencing.Results: Of 249 children included, 142 were infected with HIV; of these, 120 were ART naive, with a median age of 2.8 years (interquartile range [IQR], 1.7-4.0 years) and a median baseline CD4+ T-cell percentage of 20% (IQR, 14%-24%), and 22 were ART experienced, with a median age of 6.5 years (IQR, 5.9-9.2 years) and a median baseline CD4+ T-cell percentage of 35% (IQR, 31%-39%). The control group comprised 107 children without HIV infection. The median increase in the CD4+ T-cell percentage was 17 percentage points (IQR, 12-22 percentage points) at week 96 among ART-naive children, and the viral load was <100 copies/mL in 76% of ART-naive children and 91% of ART-experienced children. Immune activation decreased with ART use. Children could be divided on the basis of immune activation markers into the following 3 clusters: in cluster 1, the majority of children were HIV uninfected; cluster 2 comprised a mix of HIV-uninfected children and HIV-infected ART-naive or ART-experienced children; and in cluster 3, the majority were ART naive. Immune activation was low in cluster 1, decreased in cluster 3, and persisted in cluster 2. Blood microbial DNA levels were negative or very low across groups, with no difference between clusters except for Enterobacteriaceae organisms (the level was higher in cluster 1; P < .0001).Conclusion: Immune activation decreased with ART use, with marker clustering indicating different activation patterns according to HIV and ART status. Levels of bacterial DNA in blood were low regardless of HIV status, ART status, and immune activation status. Microbial translocation did not drive immune activation in this setting.Clinical Trials Registration: ISRCTN69078957. [ABSTRACT FROM AUTHOR]- Published
- 2019
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15. Overweight and stunting in migrant Hispanic children in the USA
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You, Tongjian, Yang, Rongze, Lyles, Mary F, Gong, Dawei, Nicklas, Barbara J, Wells, Jonathan C K, Weise, Antonio Suarez, Warner, Matthew J, Ozanne, Susan E, Visser, Marjolein, Bouter, Lex M, McQuillan, G. M., Wener, Mark H, Harris, Tamara B, Tzioumis, Emma, Adair, Linda S., Snell-Bergeon, Janet K., West, Nancy A, Mayer-Davis, Elizabeth J., Liese, Angela D, Marcovina, Santica M, D'Agostino, Ralph B., Hamman, Richard F, Dabelea, Dana, Sawaya, Ana Lydia, Roberts, Susan B, Prendergast, Andrew J, Humphrey, Jean H, Packard, René R S, Libby, Peter, Nakayama, Tomohiro, Wang, Zhaoxia, Mukuddem-Petersen, J, Kruger, Herculina Salome, Motie, Marjan, Evangelista, Lorraine S, Horwich, Tamara, Lombardo, Dawn, Zaldivar, Frank, Hamilton, Michele, Fonarow, Gregg C, Mcdade, Thomas W., Tallman, Paula S., Madimenos, Felicia C., Liebert, Melissa A., Cepon, Tara J., Sugiyama, Lawrence S., Snodgrass, James Josh, Martins, Paula A, Hoffman, Daniel J, Fernandes, M T B, Nascimento, C R, Sesso, R, Markowitz, Diane L, Cosminsky, Sheila, Ridker, Paul M., Maseri, Attilio, Pretorius, Rachelle, Schutte, Aletta E, Kimani-Murage, Elizabeth W., Kahn, Kathleen, Pettifor, John M, Tollman, Stephen M, Dunger, David B, Gómez-Olivé, Xavier F., Norris, Shane A, Khaodhiar, Lalita, Ling, Pei-Ra, Blackburn, George L, Bistrian, Bruce R, Jinabhai, C C, Taylor, M, Sullivan, K R, Herder, Christian, Schneitler, Sophie, Rathmann, Wolfgang, Haastert, Burkhard, Schneitler, Heiko, Winkler, Horst, Bredahl, Renate, Hahnloser, Erik, Martin, Stephan, Filla, Putu, Fernald, L C, Neufeld, L M, and Moral and Political Philosophy
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Leptin ,Male ,Dual-e ,food intake ,a obesidade vem aumentando ,poverty ,Inflammation: epidemiology ,Developmental Disabilities ,nutrition disorders ,mostrando que a ,Blood Pressure ,South Africa: epidemiology ,Comorbidity ,Global Health ,complications [Malnutrition] ,Body Mass Index ,Pregnancy ,Reference Values ,nutrition transition ,blood [Interleukin-6] ,Prospective Studies ,Child ,Children ,Growth Disorders ,metabolism [Inflammation] ,Stunting ,Schools ,iotf ,Anthropometry ,Statistics ,complications [Obesity] ,blood [Tumor Necrosis Factor-alpha] ,prevention & control [Developmental Disabilities] ,prevention & control [Obesity] ,who ,Obesity: epidemiology ,C-Reactive Protein ,nutrition ,Adipose Tissue ,african primary school children ,analysis [C-Reactive Protein] ,Body Composition ,early growth ,Obesity: metabolism ,Economic deprivation ,metabolism [Intra-Abdominal Fat] ,o risco de obesidade ,futura ,socio-economic status ,metabolism [C-Reactive Protein] ,Heart failure ,physiology [Body Composition] ,epidemiology [South Africa] ,mas também nos países ,Humans ,Nonparametric ,Endothelium ,Developing Countries ,Adipose Tissue: anatomy & histology ,analysis [Biological Markers] ,Developmental Disabilities: prevention & control ,Tumor Necrosis Factor-alpha ,Infant ,Proteins ,C-Reactive Protein: analysis ,Tumor Necrosis Factor-alpha: blood ,diagnosis [Obesity] ,Confounding Factors (Epidemiology) ,United States ,diagnosis [Inflammation] ,nutritional status ,Cross-Sectional Studies ,C-Reactive Protein: metabolism ,Social Class ,income countries ,Case-Control Studies ,Linear Models ,complications [Growth Disorders] ,metabolism [Adipose Tissue] ,anatomy & histology [Adipose Tissue] ,atherosclerosis ,Agricultural laborers ,Biomarkers ,Body Height: physiology ,double burden ,obesity ,Intra-Abdominal Fat: metabolism ,Growth ,Developmental Disabilities: epidemiology ,Body Composition: physiology ,Growth Disorders: complications ,Adipose Tissue: metabolism ,Leukocyte Count ,South Africa ,hs-crp ,Risk Factors ,Biological Markers: analysis ,metabolism [Growth Disorders] ,epidemiology [Developmental Disabilities] ,Cluster Analysis ,epidemiology [Growth Disorders] ,maternal diet ,Interleukin-6: blood ,dual burden ,indigenous ,não apenas nos países ,significativa de evidências epidemiológicas ,low- and middle ,thrifty phenotype ,physiology [Body Height] ,Photon ,Growth Disorders: epidemiology ,Plethysmography ,Obesity: prevention & control ,nutritional transition ,Biological Markers ,Female ,hypothesis ,Disease Susceptibility ,epidemiology [United States] ,type 2 diabetes ,dramaticamente ,Brazil ,em desenvolvi ,Adult ,Malnutrition: complications ,epidemiology [Inflammation] ,Adolescent ,United States: epidemiology ,Obesity: complications ,complications [Inflammation] ,Intra-Abdominal Fat ,Migrants ,Obesity: diagnosis ,Young Adult ,Inflammation: metabolism ,Sex Factors ,overnutrition ,metabolism [Obesity] ,overweight ,Absorptiometry ,coronary heart disease ,Preschool ,Inflammation ,pre-school ,epidemiology [Obesity] ,urbanisation ,resumo existe uma quantidade ,Height ,Interleukin-6 ,menarche ,Body Weight ,Malnutrition ,Undernutrition ,Newborn ,Body Height ,desenvolvidos ,Inflammation: complications ,Chronic Disease ,Growth Disorders: metabolism ,Insulin Resistance ,Inflammation: diagnosis ,Follow-Up Studies ,baixa estatura nutricional aumenta - Abstract
Obesity, type 2 diabetes mellitus (DM) and metabolic syndrome (MS) are common in patients with heart failure (HF). Studies investigating the association between known biomarkers and adiposity in patient populations are limited. The aim of the present study was to investigate the association between C-reactive protein (CRP) and leptin with adiposity in a sub-group of overweight/obese patients with HF, DM and/or MS. A total of 36 patients (mean age, 56.72±9.78 years; ranging between 27 and 76 years of age; 80.6% male; 52.8% Caucasian) were enrolled and their height, weight, waist circumference and body composition (e.g. percentage body fat and lean mass), as well as the levels of CRP and leptin, were assessed. The results demonstrated that there was a significant association between CRP and leptin, CRP and body mass index (BMI) and gender and percentage body fat (P
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- 2010
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16. Environmental enteric dysfunction pathways and child stunting: A systematic review.
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Harper, Kaitlyn M., Mutasa, Maxine, Prendergast, Andrew J., Humphrey, Jean, and Manges, Amee R.
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STUNTED growth ,HYPERPLASIA ,MEDLINE ,BIOLOGICAL tags - Abstract
Background: Environmental enteric dysfunction (EED) is commonly defined as an acquired subclinical disorder of the small intestine, characterized by villous atrophy and crypt hyperplasia. EED has been proposed to underlie stunted growth among children in developing countries. A collection of biomarkers, organized into distinct domains, has been used to measure different aspects of EED. Here, we examine whether these hypothesized relationships, among EED domains and between each domain and stunting, are supported by data from recent studies. Methodology: A systematic literature search was conducted using PubMed, MEDLINE, EMBASE, Web of Science, and CINAHL between January 1, 2010 and April 20, 2017. Information on study objective, design, population, location, biomarkers, and results were recorded, as well as qualitative and quantitative definitions of EED. Biomarkers were organized into five EED domains, and the number of studies that support or do not support relationships among domains and between each domain with stunting were summarized. Results: There was little evidence to support the pathway from intestinal permeability to microbial translocation and from microbial translocation to stunting, but stronger support existed for the link between intestinal inflammation and systemic inflammation and for intestinal inflammation and stunting. There was conflicting evidence for the pathways from intestinal damage to intestinal permeability and intestinal damage to stunting. Conclusions: These results suggest that certain EED biomarkers may require reconsideration, particularly those most difficult to measure, such as microbial translocation and intestinal permeability. We discuss several issues with currently used biomarkers and recommend further analysis of pathogen-induced changes to the intestinal microbiota as a pathway leading to stunting. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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17. Virological response and resistance among HIV-infected children receiving long-term antiretroviral therapy without virological monitoring in Uganda and Zimbabwe: Observational analyses within the randomised ARROW trial.
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Szubert, Alexander J., Prendergast, Andrew J., Spyer, Moira J., Musiime, Victor, Musoke, Philippa, Bwakura-Dangarembizi, Mutsa, Nahirya-Ntege, Patricia, Thomason, Margaret J., Ndashimye, Emmanuel, Nkanya, Immaculate, Senfuma, Oscar, Mudenge, Boniface, Klein, Nigel, Gibb, Diana M., Walker, A. Sarah, null, null, and ARROW Trial Team
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VIRAL load , *ANTIRETROVIRAL agents , *CD4 antigen , *NUCLEOSIDE reverse transcriptase inhibitors - Abstract
Background: Although WHO recommends viral load (VL) monitoring for those on antiretroviral therapy (ART), availability in low-income countries remains limited. We investigated long-term VL and resistance in HIV-infected children managed without real-time VL monitoring.Methods and Findings: In the ARROW factorial trial, 1,206 children initiating ART in Uganda and Zimbabwe between 15 March 2007 and 18 November 2008, aged a median 6 years old, with median CD4% of 12%, were randomised to monitoring with or without 12-weekly CD4 counts and to receive 2 nucleoside reverse transcriptase inhibitors (2NRTI, mainly abacavir+lamivudine) with a non-nucleoside reverse transcriptase inhibitor (NNRTI) or 3 NRTIs as long-term ART. All children had VL assayed retrospectively after a median of 4 years on ART; those with >1,000 copies/ml were genotyped. Three hundred and sixteen children had VL and genotypes assayed longitudinally (at least every 24 weeks). Overall, 67 (6%) switched to second-line ART and 54 (4%) died. In children randomised to WHO-recommended 2NRTI+NNRTI long-term ART, 308/378 (81%) monitored with CD4 counts versus 297/375 (79%) without had VL <1,000 copies/ml at 4 years (difference = +2.3% [95% CI -3.4% to +8.0%]; P = 0.43), with no evidence of differences in intermediate/high-level resistance to 11 drugs. Among children with longitudinal VLs, only 5% of child-time post-week 24 was spent with persistent low-level viraemia (80-5,000 copies/ml) and 10% with VL rebound ≥5,000 copies/ml. No child resuppressed <80 copies/ml after confirmed VL rebound ≥5,000 copies/ml. A median of 1.0 (IQR 0.0,1.5) additional NRTI mutation accumulated over 2 years' rebound. Nineteen out of 48 (40%) VLs 1,000-5,000 copies/ml were immediately followed by resuppression <1,000 copies/ml, but only 17/155 (11%) VLs ≥5,000 copies/ml resuppressed (P < 0.0001). Main study limitations are that analyses were exploratory and treatment initiation used 2006 criteria, without pre-ART genotypes.Conclusions: In this study, children receiving first-line ART in sub-Saharan Africa without real-time VL monitoring had good virological and resistance outcomes over 4 years, regardless of CD4 monitoring strategy. Many children with detectable low-level viraemia spontaneously resuppressed, highlighting the importance of confirming virological failure before switching to second-line therapy. Children experiencing rebound ≥5,000 copies/ml were much less likely to resuppress, but NRTI resistance increased only slowly. These results are relevant to the increasing numbers of HIV-infected children receiving first-line ART in sub-Saharan Africa with limited access to virological monitoring.Trial Registration: ISRCTN Registry, ISRCTN24791884. [ABSTRACT FROM AUTHOR]- Published
- 2017
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18. Universal antiretroviral therapy for HIV-infected children: a review of the benefits and risks to consider during implementation.
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Barlow-Mosha, Linda, Musiime, Victor, Davies, Mary-Ann, Prendergast, Andrew J., Musoke, Philippa, Siberry, George, and Penazzato, Martina
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HIV infections ,THERAPEUTICS ,ANTIRETROVIRAL agents ,DRUG toxicity ,CHILDREN'S health - Abstract
Background: The 2016 World Health Organization (WHO) consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection, recommended to start all HIV-infected children on antiretroviral therapy (ART). Here, we explore the possible benefits and risks of implementing universal ART for all HIV-infected children and adolescents and outline some of the key considerations that led to the 2016 revision of WHO guidelines. Methods: We conducted a review of the published data from 2000 to 2016, to ascertain the clinical and programmatic benefits, as well as the risks of implementing universal ART for all children. Results and discussion: Universal ART for all children has the potential to increase treatment coverage, which in 2015 was only 51% globally, as well as providing several biological benefits, by preventing: premature death/loss to follow-up, progressive destruction of the immune system, poor growth and pubertal delay, poor neuro-cognitive outcomes and future burden to the health care system with complications of untreated HIV-infection. However, the strategy could be associated with risks, notably development of HIV drug resistance, antiretroviral drug toxicities and increased costs to an already stretched health system. Conclusion: Overall, our findings suggest that the benefits could outweigh the risks and support universal ART for all HIV-infected children, but recognize that national programmes will need to put measures in place to minimize the risks if they choose to implement the strategy. [ABSTRACT FROM AUTHOR]
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- 2017
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19. Baseline Inflammatory Biomarkers Identify Subgroups of HIV-Infected African Children With Differing Responses to Antiretroviral Therapy.
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Prendergast, Andrew J., Szubert, Alexander J., Berejena, Chipo, Pimundu, Godfrey, Pala, Pietro, Shonhai, Annie, Musiime, Victor, Bwakura-Dangarembizi, Mutsa, Poulsom, Hannah, Hunter, Patricia, Musoke, Philippa, Kihembo, Macklyn, Munderi, Paula, Gibb, Diana M., Spyer, Moira, Walker, A. Sarah, Klein, Nigel, and ARROW Trial Team
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BIOMARKERS , *BIOCHEMISTRY , *BIOINDICATORS , *HIV-positive children , *HIV-positive persons , *ANTIRETROVIRAL agents , *ANTIGENS , *C-reactive protein , *HIV , *HIV infections , *INFLAMMATION , *INTERLEUKINS , *LONGITUDINAL method , *RESEARCH funding , *STATISTICAL sampling , *SURVIVAL analysis (Biometry) , *TUMOR necrosis factors , *VIRAL load , *RANDOMIZED controlled trials , *ANTI-HIV agents , *CD4 lymphocyte count - Abstract
Background: Identifying determinants of morbidity and mortality may help target future interventions for human immunodeficiency virus (HIV)-infected children.Methods: CD4(+) T-cell count, HIV viral load, and levels of biomarkers (C-reactive protein, tumor necrosis factor α [TNF-α], interleukin 6 [IL-6], and soluble CD14) and interleukin 7 were measured at antiretroviral therapy (ART) initiation in the ARROW trial (case-cohort design). Cases were individuals who died, had new or recurrent World Health Organization clinical stage 4 events, or had poor immunological response to ART.Results: There were 115 cases (54 died, 45 had World Health Organization clinical stage 4 events, and 49 had poor immunological response) and 485 controls. Before ART initiation, the median ages of cases and controls were 8.2 years (interquartile range [IQR], 4.4-11.4 years) and 5.8 years (IQR, 2.3-9.3 years), respectively, and the median percentages of lymphocytes expressing CD4 were 4% (IQR, 1%-9%) and 13% (IQR, 8%-18%), respectively. In multivariable logistic regression, cases had lower age-associated CD4(+) T-cell count ratio (calculated as the ratio of the subject's CD4(+) T-cell count to the count expected in healthy individuals of the same age; P < .0001) and higher IL-6 level (P = .002) than controls. Clustering biomarkers and age-associated CD4(+) and CD8(+) T-cell count ratios identified 4 groups of children. Group 1 had the highest frequency of cases (41% cases; 16% died) and profound immunosuppression; group 2 had similar mortality (23% cases; 15% died), but children were younger, with less profound immunosuppression and high levels of inflammatory biomarkers and malnutrition; group 3 comprised young children with moderate immunosuppression, high TNF-α levels, and high age-associated CD8(+) T-cell count ratios but lower frequencies of events (12% cases; 7% died); and group 4 comprised older children with low inflammatory biomarker levels, lower HIV viral loads, and good clinical outcomes (11% cases; 5% died).Conclusions: While immunosuppression is the major determinant of poor outcomes during ART, baseline inflammation is an additional important factor, identifying a subgroup of young children with similar mortality. Antiinflammatory interventions may help improve outcomes. [ABSTRACT FROM AUTHOR]- Published
- 2016
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20. Malnutrition and vaccination in developing countries.
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Prendergast, Andrew J.
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MALNUTRITION treatment , *VACCINATION , *IMMUNODEFICIENCY , *IMMUNOLOGIC diseases , *IMMUNOGENETICS ,DEVELOPING countries - Abstract
Malnutrition contributes to an estimated 45% of deaths among children under 5 years of age in developing countries, predominantly due to infections. Malnourished children therefore stand to benefit hugely from vaccination, but malnutrition has been described as the most common immunodeficiency globally, suggesting that they may not be able to respond effectively to vaccines. The immunology of malnutrition remains poorly characterized, but is associated with impairments in mucosal barrier integrity, and innate and adaptive immune dysfunction. Despite this, the majority of malnourished children can mount a protective immune response following vaccination, although the timing, quality and duration of responses may be impaired. This paper reviews the evidence for vaccine immunogenicity in malnourished children, discusses the importance of vaccination in prevention of malnutrition and highlights evidence gaps in our current knowledge. [ABSTRACT FROM AUTHOR]
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- 2015
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21. The implications of three major new trials for the effect of water, sanitation and hygiene on childhood diarrhea and stunting: a consensus statement.
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Cumming, Oliver, Arnold, Benjamin F, Ban, Radu, Clasen, Thomas, Esteves Mills, Joanna, Freeman, Matthew C, Gordon, Bruce, Guiteras, Raymond, Howard, Guy, Hunter, Paul R, Johnston, Richard B, Pickering, Amy J, Prendergast, Andrew J, Prüss-Ustün, Annette, Rosenboom, Jan Willem, Spears, Dean, Sundberg, Shelly, Wolf, Jennyfer, Null, Clair, and Luby, Stephen P
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NEW trials ,SANITATION ,CHILDREN ,HYGIENE ,DIARRHEA - Abstract
Background: Three large new trials of unprecedented scale and cost, which included novel factorial designs, have found no effect of basic water, sanitation and hygiene (WASH) interventions on childhood stunting, and only mixed effects on childhood diarrhea. Arriving at the inception of the United Nations' Sustainable Development Goals, and the bold new target of safely managed water, sanitation and hygiene for all by 2030, these results warrant the attention of researchers, policy-makers and practitioners.Main Body: Here we report the conclusions of an expert meeting convened by the World Health Organization and the Bill and Melinda Gates Foundation to discuss these findings, and present five key consensus messages as a basis for wider discussion and debate in the WASH and nutrition sectors. We judge these trials to have high internal validity, constituting good evidence that these specific interventions had no effect on childhood linear growth, and mixed effects on childhood diarrhea. These results suggest that, in settings such as these, more comprehensive or ambitious WASH interventions may be needed to achieve a major impact on child health.Conclusion: These results are important because such basic interventions are often deployed in low-income rural settings with the expectation of improving child health, although this is rarely the sole justification. Our view is that these three new trials do not show that WASH in general cannot influence child linear growth, but they do demonstrate that these specific interventions had no influence in settings where stunting remains an important public health challenge. We support a call for transformative WASH, in so much as it encapsulates the guiding principle that - in any context - a comprehensive package of WASH interventions is needed that is tailored to address the local exposure landscape and enteric disease burden. [ABSTRACT FROM AUTHOR]- Published
- 2019
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22. The impact of antibiotics on growth in children in low and middle income countries: systematic review and meta-analysis of randomised controlled trials.
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Gough, Ethan K., Moodie, Erica E. M., Prendergast, Andrew J., Johnson, Sarasa M. A., Humphrey, Jean H., Stoltzfus, Rebecca J., Walker, A. Sarah, Trehan, Indi, Gibb, Diana M., Rie Goto, Tahan, Soraia, Batista de Morais, Mauro, and Manges, Amee R.
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ANTIBIOTICS ,CHILD development ,CONFIDENCE intervals ,INFANT development ,META-analysis ,SYSTEMATIC reviews ,DESCRIPTIVE statistics ,CHILDREN - Abstract
The article presents a systematic review and meta-analysis of randomised controlled trials as of mid-April 2014 to examine the effect of antibiotics on the growth of children in low and middle income countries. It claims that antibiotics are recommended by the World Health Organization to treat severely malnourished children and those infected or exposed to HIV. In the study, data from Medline, Embase, Scopus and the Cochrane central registers were examined.
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- 2014
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