Research Article (New England Journal of Medicine) Severe anemia in Malawian children

Background: Severe anemia is a major cause of sickness and death in African children, yet the causes of anemia in this population have been inadequately studied.Methods: We conducted a case–control study of 381 preschool children with severe anemia (hemoglobin concentration, <5.0 g per deciliter) and 757 preschool children without severe anemia in urban and rural settings in Malawi. Causal factors  previously associated with severe anemia were studied. The data were examined by multivariate analysis and structural equation modeling.Results: Bacteremia (adjusted odds ratio, 5.3; 95% confidence interval [CI], 2.6 to 10.9), malaria (adjusted odds ratio, 2.3; 95% CI, 1.6 to 3.3), hookworm (adjusted odds ratio, 4.8; 95% CI, 2.0 to 11.8), human immunodeficiency virus infection (adjusted odds ratio, 2.0; 95% CI, 1.0 to 3.8), the G6PD−202/−376 genetic disorder (adjusted odds ratio, 2.4; 95% CI, 1.3 to 4.4), vitamin A deficiency (adjusted odds ratio, 2.8; 95% CI, 1.3 to 5.8), and vitamin B12 deficiency (adjusted odds ratio, 2.2; 95% CI, 1.4 to 3.6) were associated with severe anemia. Folate deficiency, sickle cell disease, and laboratory signs of an abnormal  inflammatory response were uncommon. Iron deficiency was not prevalent in case patients (adjusted odds ratio, 0.37; 95% CI, 0.22 to 0.60) and was negatively associated with bacteremia. Malaria was associated with severe anemia in the urban site (with seasonal transmission) but not in the rural site (where malaria was holoendemic). Seventy-six percent of hookworm infections were found in children under 2 years of age.Conclusions: There are multiple causes of severe anemia in Malawian preschool children, but folate and iron deficiencies are not prominent among them. Even in the presence of malaria parasites, additional or alternative causes of severe anemia should be considered

HIV-associated anemia in children: a systematic review from a global perspective

OBJECTIVES: To assess the importance of anemia in HIV-infected children in western and tropical settings. DESIGN: A systematic review with a descriptive component. METHODS: Four databases were searched and reference lists of pertinent articles were checked. Studies that reported data on anemia or hemoglobin levels in HIV-infected children were selected and grouped according to the location and the definition of anemia. RESULTS: Thirty-six studies met the inclusion criteria. Mild (hemoglobin <11 g/dl) and moderate (hemoglobin <9 g/dl) anemia were more prevalent with HIV infection (odds ratio 4.5; 95% confidence interval 2.5-8.3 and odds ratio 4.5; 95% confidence interval 2.0-10.3, respectively). Mean hemoglobin levels were lower (standardized mean difference; 0.79; 95% confidence interval 0.47-1.10). These differences were observed in both western and tropical settings. Anemia incidence ranged from 0.41 to 0.44 per person-year. There was limited data on more severe anemia (hemoglobin <7 or <5 g/dl). As anemia was frequently identified as an independent risk factor for disease progression and death, we next reviewed the limited data to formulate better strategies. Failure of erythropoiesis was the most important mechanism for anemia in HIV-infected children. Therapeutic options include highly active antiretroviral therapy and prevention or treatment of secondary infections. Erythropoietin can improve anemia in children, but it has not been evaluated in developing countries. Micronutrient supplementation may be helpful in individual children. The potential benefits or risks of iron supplementation in HIV-infected children require evaluation. CONCLUSION: Anemia is a very common complication of pediatric HIV infection, associated with a poor prognosis. With the increasing global availability of highly active antiretroviral therapy, more data on the safety and efficacy of possible interventions in children are urgently needed

Descriptive data of the development and validation cohort.

Descriptive data of the development and validation cohort.</p

Area under receiver operating characteristic curve (AUC) for each score for predicting mortality in the development cohort.

Area under receiver operating characteristic curve (AUC) for each score for predicting mortality in the development cohort.</p

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Table A: Inclusion criteria of the development and validation cohorts Table B: Components of the LqSOFA Table C: Cut-off values for heart and respiratory rate in different guidelines Table D: Components of the FEAST-PET Table E: Components of the BqSOFA Table F: Univariate analysis of (possible) predictors for in-hospital mortality in the development cohort Table G: Stepwise approach amending the LqSOFA to develop the BqSOFA Table H: BqSOFA compared to FEAST-PET (Net Reclassification Index) Fig A: Flow diagram included children in development and validation cohort Fig B: Comparison of cut-off values for heart rate and respiratory rate in different guidelines and studies (DOCX)</p

Prognostic performance of LqSOFA, BqSOFA and FEAST-PET score in development cohort.

Prognostic performance of LqSOFA, BqSOFA and FEAST-PET score in development cohort.</p

Prognostic performance of LqSOFA, BqSOFA and FEAST-PET in the validation cohort.

Prognostic performance of LqSOFA, BqSOFA and FEAST-PET in the validation cohort.</p

Bar charts of LqSOFA, BqSOFA and FEAST-PET in the validation cohort.

Bar charts of LqSOFA, BqSOFA and FEAST-PET in the validation cohort.</p

Area under receiver operating characteristic curve (AUC) for each score for predicting mortality in the validation cohort.

Area under receiver operating characteristic curve (AUC) for each score for predicting mortality in the validation cohort.</p

Inclusivity in global research.

In low-resource settings, a reliable bedside score for timely identification of children at risk of dying, could help focus resources and improve survival. The rapid bedside Liverpool quick Sequential Organ Failure Assessment (LqSOFA) uses clinical parameters only and performed well in United Kingdom cohorts. A similarly quick clinical assessment-only score has however not yet been developed for paediatric populations in sub-Saharan Africa. In a development cohort of critically ill children in Malawi, we calculated the LqSOFA scores using age-adjusted heart rate and respiratory rate, capillary refill time and Blantyre Coma Scale, and evaluated its prognostic performance for mortality. An improved score, the Blantyre qSOFA (BqSOFA), was developed (omitting heart rate, adjusting respiratory rate cut-off values and adding pallor), subsequently validated in a second cohort of Malawian children, and compared with an existing score (FEAST-PET). Prognostic performance for mortality was evaluated using area under the receiver operating characteristic curve (AUC). Mortality was 15.4% in the development (N = 493) and 22.0% in the validation cohort (N = 377). In the development cohort, discriminative ability (AUC) of the LqSOFA to predict mortality was 0.68 (95%-CI: 0.60–0.76). The BqSOFA and FEAST-PET yielded AUCs of 0.84 (95%-CI:0.79–0.89) and 0.83 (95%-CI:0.77–0.89) in the development cohort, and 0.74 (95%-CI:0.68–0.79) and 0.76 (95%-CI:0.70–0.82) in the validation cohort, respectively. We developed a simple prognostic score for Malawian children based on four clinical parameters which performed as well as a more complex score. The BqSOFA might be used to promptly identify critically ill children at risk of dying and prioritize hospital care in low-resource settings.</div