Autoantibody levels are associated with acute kidney injury, anemia and post-discharge morbidity and mortality in Ugandan children with severe malaria.
Ontology highlight
ABSTRACT:
SUBMITTER: Rivera-Correa J
PROVIDER: S-EPMC6797715 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
Publications
Autoantibody levels are associated with acute kidney injury, anemia and post-discharge morbidity and mortality in Ugandan children with severe malaria.
Rivera-Correa Juan J Conroy Andrea L AL Opoka Robert O RO Batte Anthony A Namazzi Ruth R Ouma Benson B Bangirana Paul P Idro Richard R Schwaderer Andrew L AL John Chandy C CC Rodriguez Ana A
Scientific reports 20191017 1
Autoantibodies targeting host antigens contribute to autoimmune disorders, frequently occur during and after infections and have been proposed to contribute to malaria-induced anemia. We measured anti-phosphatidylserine (PS) and anti-DNA antibody levels in 382 Ugandan children prospectively recruited in a study of severe malaria (SM). High antibody levels were defined as antibody levels greater than the mean plus 3 standard deviations of community children (CC). We observed increases in median l ...[more]
Similar Datasets
Project description:BackgroundGlobally, 85% of acute kidney injury (AKI) cases occur in low-and-middle-income countries. There is limited information on persistent kidney disease (acute kidney disease [AKD]) following severe malaria-associated AKI.MethodsBetween March 28, 2014, and April 18, 2017, 598 children with severe malaria and 118 community children were enrolled in a two-site prospective cohort study in Uganda and followed up for 12 months. The Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to define AKI (primary exposure) and AKD at 1-month follow-up (primary outcome). Plasma neutrophil gelatinase-associated lipocalin (NGAL) was assessed as a structural biomarker of AKI.FindingsThe prevalence of AKI was 45·3% with 21·5% of children having unresolved AKI at 24 h. AKI was more common in Eastern Uganda. In-hospital mortality increased across AKI stages from 1·8% in children without AKI to 26·5% with Stage 3 AKI (p < 0·0001). Children with a high-risk plasma NGAL test were more likely to have unresolved AKI (OR, 7·00 95% CI 4·16 to 11·76) and die in hospital (OR, 6·02 95% CI 2·83 to 12·81). AKD prevalence was 15·6% at 1-month follow-up with most AKD occurring in Eastern Uganda. Risk factors for AKD included severe/unresolved AKI, blackwater fever, and a high-risk NGAL test (adjusted p < 0·05). Paracetamol use during hospitalization was associated with reduced AKD (p < 0·0001). Survivors with AKD post-AKI had higher post-discharge mortality (17·5%) compared with children without AKD (3·7%).InterpretationChildren with severe malaria-associated AKI are at risk of AKD and post-discharge mortality.FundingThis work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke (R01NS055349 to CCJ) and the Fogarty International Center (D43 TW010928 to CCJ), and a Ralph W. and Grace M. Showalter Young Investigator Award to ALC.
| S-EPMC8850340 | biostudies-literature
Project description:BACKGROUND:Severe malarial anaemia is one of the leading causes of paediatric hospital admissions in Malawi. Post-discharge malaria chemoprevention (PMC) is the intermittent administration of full treatment courses of antimalarial to children recovering from severe anaemia and findings suggest that this intervention significantly reduces readmissions and deaths in these children. Community delivery of health interventions utilizing community health workers (CHWs) has been successful in some programmes and not very positive in others. In Malawi, there is an on-going cluster randomised trial that aims to find the optimum strategy for delivery of dihydroartemesinin-piperaquine (DHP) for PMC in children with severe anaemia. Our qualitative study aimed to explore the feasibility of utilizing CHWs also known as health surveillance assistants (HSAs) to remind caregivers to administer PMC medication in the existing Malawian health system. METHODS:Between December 2016 and March 2018, 20 individual in-depth-interviews (IDIs) and 2 focus group discussions (FGDs) were conducted with 39 HSAs who had the responsibility of conducting home visits to remind caregivers of children who were prescribed PMC medication in the trial. All interviews were conducted in the local language, transcribed verbatim, and translated into English. The transcripts were uploaded to NVIVO 11 and analysed using the thematic framework analysis method. RESULTS:Although intrinsic motivation was reportedly high, adherence to the required number of home visits was very poor with only 10 HSAs reporting full adherence. Positive factors for adherence were the knowledge and perception of the effectiveness of PMC and the recognition from the community as well as health system. Poor training, lack of supervision, high workload, as well as technical and structural difficulties; were reported barriers to adherence by the HSAs. CONCLUSIONS:Post-discharge malaria chemoprevention with DHP is perceived as a positive approach to manage children recovering from severe anaemia by HSAs in Malawi. However, adherence to home visit reminders was very poor and the involvement of HSAs in a scale up of this intervention may pose a challenge in the existing Malawian health system. TRIAL REGISTRATION:ClinicalTrials.gov identifier NCT02721420 . The trial was registered on 26 March 2016.
| S-EPMC6299958 | biostudies-literature
Project description:High mortality after discharge from hospital following acute illness has been observed among children with Severe Acute Malnutrition (SAM). However, mechanisms that may be amenable to intervention to reduce risk are unknown. We performed a nested case-control study among HIV-uninfected children aged 2-59 months treated for complicated SAM according to WHO recommendations at four Kenyan hospitals. Blood was drawn from 1778 children when clinically judged stable before discharge from hospital. Cases were children who died within 60 days. Controls were randomly selected children who survived for one year without readmission to hospital. Untargeted proteomics, total protein, cytokines and chemokines, and leptin were assayed in plasma and corresponding biological processes determined. Among 121 cases and 120 controls, increased levels of calprotectin, von Willebrand factor, angiotensinogen, IL8, IL15, IP10, TNFα, and decreased levels of leptin, heparin cofactor 2, and serum paraoxonase were associated with mortality after adjusting for possible confounders. Acute phase responses, cellular responses to lipopolysaccharide, neutrophil responses to bacteria, and endothelial responses were enriched among cases. Among apparently clinically stable children with SAM, a sepsis-like profile is associated with subsequent death. This may be due to ongoing bacterial infection, translocated bacterial products or deranged immune response during nutritional recovery.
| S-EPMC6461700 | biostudies-literature
Project description:BackgroundAcute kidney injury (AKI) is a risk factor for neurocognitive impairment in severe malaria (SM), but the impact of AKI on long-term behavioral outcomes following SM is unknown.MethodsWe conducted a prospective study on behavioral outcomes of Ugandan children 1.5 to 12 years of age with two forms of severe malaria, cerebral malaria (CM, n = 226) or severe malarial anemia (SMA, n = 214), and healthy community children (CC, n = 173). AKI was defined as a 50% increase in creatinine from estimated baseline. Behavior and executive function were assessed at baseline and 6, 12, and 24 months later using the Child Behavior Checklist and Behavior Rating Inventory of Executive Function, respectively. Age-adjusted z-scores were computed for each domain based on CC scores. The association between AKI and behavioral outcomes was evaluated across all time points using linear mixed effect models, adjusting for sociodemographic variables and disease severity.ResultsAKI was present in 33.2% of children with CM or SMA at baseline. Children ≥6 years of age with CM or SMA who had AKI on admission had worse scores in socio-emotional function in externalizing behaviors (Beta (95% CI), 0.52 (0.20, 0.85), p = 0.001), global executive function (0.48 (0.15, 0.82), p = 0.005) and behavioral regulation (0.66 (0.32, 1.01), p = 0.0002) than children without AKI. There were no behavioral differences associated with AKI in children <6 years of age.ConclusionsAKI is associated with long-term behavioral problems in children ≥6 years of age with CM or SMA, irrespective of age at study enrollment.
| S-EPMC6917349 | biostudies-literature
Project description:BACKGROUND:In resource limited settings, there is variability in the level of adherence to clinical guidelines in the inpatient management of children with common conditions like severe anemia. However, there is limited data on the effect of adherence to clinical guidelines on inpatient mortality in children managed for severe anemia. METHODS:We analyzed data from an uncontrolled before and after in-service training intervention to improve quality of care in Lira and Jinja regional referral hospitals in Uganda. Inpatient records of children aged 0 to 5 years managed as cases of 'severe anemia (SA)' were reviewed to ascertain adherence to clinical guidelines and compare inpatient deaths in SA children managed versus those not managed according to clinical guidelines. Logistic regression analysis was conducted to evaluate the relationship between clinical care factors and inpatient deaths amongst patients managed for SA. RESULTS:A total of 1,131 children were assigned a clinical diagnosis of 'severe anemia' in the two hospitals. There was improvement in the level of care after the in-service training intervention with more children being managed according to clinical guidelines compared to the period before, 218/510 (42.7%) vs 158/621 (25.4%) (p < 0.001). Overall, children managed according to clinical guidelines had reduced risk of inpatient mortality compared to those not managed according to clinical guidelines, [OR 0.28, (95%, CI 0.14, 0.55), p = 0.001]. Clinical care factors associated with decreased risk of inpatient death included, having pre-transfusion hemoglobin done to confirm diagnosis [OR 0.5; 95% CI 0.29, 0.87], a co-morbid diagnosis of severe malaria [OR 0.4; 95% CI 0.25, 0.76], and being reviewed after admission by a clinician [OR 0.3; 95% CI 0.18, 0.59], while a co-morbid diagnosis of severe acute malnutrition was associated with increased risk of inpatient death [OR 4.2; 95% CI 2.15, 8.22]. CONCLUSION:Children with suspected SA who are managed according to clinical guidelines have lower in-hospital mortality than those not managed according to the guidelines. Efforts to reduce inpatient mortality in SA children in resource-limited settings should focus on training and supporting health workers to adhere to clinical guidelines.
| S-EPMC6347145 | biostudies-literature
Project description:In order to decrease cost and increase healthcare quality there is an ongoing effort to reduce readmissions after complex operations. The timing and severity of post-discharge complications after hepatectomy need to be better defined.All patients undergoing liver resection at a single institution from Jan 2009-Jun 2015 were included. Complications were scored using the comprehensive complication index (CCI). Multivariate analysis is performed using logistic regression. Receiver operating characteristics (ROCs) were analyzed to optimize the Readmission Risk Index (RRI).Of the 258 patients that met the inclusion criteria, 26 (10%) were readmitted within 30 days of discharge after hepatectomy. On multivariate analysis age ?68 years (OR 3.76; 95% CI 1.47-9.63, p = 0.006), CCI ? 15 (OR 3.65; 95% CI 1.39-9.56, p = 0.008), maximum temperature within 48 h of discharge (OR 3.02; 95% CI 1.17-7.75, p = 0.022) and white blood cell count ?10.2 billion cells/L within 48 h of discharge (OR 2.88; 95% CI 1.04-8, p = 0.043) were independent predictors of 30-day readmission. These variables were used to develop the RRI (ROC area 0.80; 95% CI 0.70-0.9, p < 0.001).The CCI and pre-discharge variables can help identify individuals at risk of readmission. Readmission risk reduction efforts should focus on this subset of patients.
| S-EPMC5509751 | biostudies-literature
Project description:Children recovering from severe malarial anaemia (SMA) remain at high risk of readmission and death after discharge from hospital. However, a recent trial found that post-discharge malaria chemoprevention (PDMC) with dihydroartemisinin-piperaquine reduces this risk. We developed a mathematical model describing the daily incidence of uncomplicated and severe malaria requiring readmission among 0-5-year old children after hospitalised SMA. We fitted the model to a multicentre clinical PDMC trial using Bayesian methods and modelled the potential impact of PDMC across malaria-endemic African countries. In the 20 highest-burden countries, we estimate that only 2-5 children need to be given PDMC to prevent one hospitalised malaria episode, and less than 100 to prevent one death. If all hospitalised SMA cases access PDMC in moderate-to-high transmission areas, 38,600 (range 16,900-88,400) malaria-associated readmissions could be prevented annually, depending on access to hospital care. We estimate that recurrent SMA post-discharge constitutes 19% of all SMA episodes in moderate-to-high transmission settings.
| S-EPMC9876927 | biostudies-literature
Project description:BackgroundDischarge diagnoses are used to track national trends and patterns of maternal morbidity. There are few data regarding the validity of the International Classification of Diseases (ICD) codes used for this purpose. The goal of our study was to try to better understand the validity of administrative data being used to monitor and assess trends in morbidity.MethodsHospital stay billing records were queried to identify all delivery admissions at the Massachusetts General Hospital for the time period 2001 to 2011 and the University of Michigan Health System for the time period 2005 to 2011. From this, we identified patients with ICD-9-Clinical Modification (CM) diagnosis and procedure codes indicative of severe maternal morbidity. Each patient was classified with 1 of 18 different medical/obstetric categories (conditions or procedures) based on the ICD-9-CM code that was recorded. Within each category, 20 patients from each institution were selected at random, and the corresponding medical charts were reviewed to determine whether the ICD-9-CM code was assigned correctly. The percentage of correct codes for each of 18 preselected clinical categories was calculated yielding a positive predictive value (PPV) and 99% confidence interval (CI).ResultsThe overall number of correctly assigned ICD-9-CM codes, or PPV, was 218 of 255 (86%; CI, 79%-90%) and 154 of 188 (82%; CI, 74%-88%) at Massachusetts General Hospital and University of Michigan Health System, respectively (combined PPV, 372/443 [84%; CI, 79-88%]). Codes within 4 categories (Hysterectomy, Pulmonary edema, Disorders of fluid, electrolyte and acid-base balance, and Sepsis) had a 99% lower confidence limit ≥75%. Codes within 8 additional categories demonstrated a 99% lower confidence limit between 74% and 50% (Acute respiratory distress, Ventilation, Other complications of obstetric surgery, Disorders of coagulation, Cardiomonitoring, Acute renal failure, Thromboembolism, and Shock). Codes within 6 clinical categories demonstrated a 99% lower confidence limit <50% (Puerperal cerebrovascular disorders, Conversion of cardiac rhythm, Acute heart failure [includes arrest and fibrillation], Eclampsia, Neurotrauma, and Severe anesthesia complications).ConclusionsICD-9-CM codes capturing severe maternal morbidity during delivery hospitalization demonstrate a range of PPVs. The PPV was high when objective supportive evidence, such as laboratory values or procedure documentation supported the ICD-9-CM code. The PPV was low when greater judgment, interpretation, and synthesis of the clinical data (signs and symptoms) was required to support a code, such as with the category Severe anesthesia complications. As a result, these codes should be used for administrative research with more caution compared with codes primarily defined by objective data.
| S-EPMC7481827 | biostudies-literature
Project description:BackgroundThe provision of post-discharge malaria chemoprevention (PMC) in children recently admitted with severe anemia reduces the risk of death and re-admissions in malaria endemic countries. The main objective of this trial was to identify the most effective method of delivering dihydroartemesinin-piperaquine to children recovering from severe anemia.MethodsThis was a 5-arm, cluster-randomized trial among under-5 children hospitalized with severe anemia at Zomba Central Hospital in Southern Malawi. Children were randomized to receive three day treatment doses of dihydroartemesinin-piperaquine monthly either; 1) in the community without a short text reminder; 2) in the community with a short message reminder; 3) in the community with a community health worker reminder; 4) at the facility without a short text reminder; or 5) at the facility with a short message reminder. The primary outcome measure was adherence to all treatment doses of dihydroartemesinin-piperaquine and this was assessed by pill-counts done by field workers during home visits. Poisson regression was utilized for analysis.ResultsBetween March 2016 and October 2018, 1460 clusters were randomized. A total of 667 children were screened and 375 from 329 clusters were eligible and enrolled from the hospital. Adherence was higher in all three community-based compared to the two facility-based delivery (156/221 [70·6%] vs. 78/150 [52·0%], IRR = 1·24,95%CI 1·06-1·44, p = 0·006). This was observed in both the SMS group (IRR = 1·41,1·21-1·64, p<0·001) and in the non-SMS group (IRR = 1·37,1·18-1·61, p<0·001). Although adherence was higher among SMS recipients (98/148 66·2%] vs. non-SMS 82/144 (56·9%), there was no statistical evidence that SMS reminders resulted in greater adherence ([IRR = 1·03,0·88-1·21, p = 0·68). When compared to the facility-based non-SMS arm (control arm), community-based delivery utilizing CHWs resulted in higher adherence [39/76 (51·3%) vs. 54/79 (68·4%), IRR = 1·32, 1·14-1·54, p<0·001].InterpretationCommunity-based delivery of dihydroartemesinin-piperaquine for post-discharge malaria chemoprevention in children recovering from severe anemia resulted in higher adherence compared to facility-based methods.Trial registrationNCT02721420; ClinicalTrials.gov.
| S-EPMC8432777 | biostudies-literature
Project description:BackgroundCerebral malaria is the most severe neurological complication of falciparum malaria and a leading cause of death and neuro-disability in sub-Saharan Africa. This study aimed to describe functional deficits and behaviour problems in children who survived cerebral malaria with severe neurological sequelae and identify patterns of brain injury.FindingsRecords of children attending a specialist child neurology clinic in Uganda with severe neurological sequelae following cerebral malaria between January 2007 and December 2008 were examined to describe deficits in gross motor function, speech, vision and hearing, behaviour problems or epilepsy. Deficits were classified according to the time of development and whether their distribution suggested a focal or generalized injury. Any resolution during the observation period was also documented.Thirty children with probable exposure to cerebral malaria attended the clinic. Referral information was inadequate to exclude other diagnoses in 7 children and these were excluded. In the remaining 23 patients, the commonest severe deficits were spastic motor weakness (14), loss of speech (14), hearing deficit (9), behaviour problems (11), epilepsy (12), blindness (12) and severe cognitive impairment (9). Behaviour problems included hyperactivity, impulsiveness and inattentiveness as in attention deficit hyperactivity disorder (ADHD) and conduct disorders with aggressive, self injurious or destructive behaviour. Two patterns were observed; a) immediate onset deficits present on discharge and b) late onset deficits. Some deficits e.g. blindness, resolved within 6 months while others e.g. speech, showed little improvement over the 6-months follow-up.ConclusionsIn addition to previously described neurological and cognitive sequelae, severe behaviour problems may follow cerebral malaria in children. The observed differences in patterns of sequelae may be due to different pathogenic mechanisms, brain regions affected or extent of injury. Cerebral malaria may be used as a new model to study the pathogenesis of ADHD.
| S-EPMC2861066 | biostudies-literature