Long Term Outcome of Severe Anaemia in Malawian Children

Severe anaemia is a common, frequently fatal, condition in African children admitted to hospital, but its long term outcome is unknown. Early reports that survivors may be at risk of additional late morbidity and mortality may have significant implications for child survival in Africa. We assessed the short and long term outcome of severe anaemia in Malawian children and identified potential risk factors for death and further severe anaemia. For 18 months, we followed up children (6-60 months old) presenting to hospital with severe anaemia (haemoglobin <or=5 g/dl) and their hospital and community controls with the aim to compare all cause mortality and severe anaemia recurrence rates between the groups, and to identify risk factors for these adverse outcomes. A total of 377 cases, 377 hospital controls and 380 community controls were recruited. Among cases, the in-hospital mortality was 6.4% and post-discharge all cause mortality was 12.6%, which was significantly greater than in hospital controls (2.9%) or community controls (1.4%) (Log rank test, p <0.001). The incidence of recurrence of severe anaemia among the cases was 0.102 per child-year (95% Confidence Interval 0.075-0.138), and was significantly higher than the 0.007 per child-year (95% CI 0.003-0.015) in the combined controls (p <0.0001). HIV was the most important risk factor both for post-discharge mortality (Hazard Ratio 10.5, 95% CI 4.0-27.2) and for recurrence of severe anaemia (HR 5.6, 95% CI 1.6-20.1). Severe anaemia carries a high 'hidden' morbidity and mortality occurring in the months after initial diagnosis and treatment. Because severe anaemia is very common, this is likely to contribute importantly to overall under-five mortality. If not adequately addressed, severe anaemia may be an obstacle to achievement of the Millennium development goal No.4 on child survival. Strategies to diagnose and properly treat HIV infected children early most likely will reduce the high post-discharge mortality in severe anaemi

Pathophysiological Mechanisms of Severe Anaemia in Malawian Children

BACKGROUND: Severe anaemia is a major cause of morbidity and mortality in African children. The aetiology is multi-factorial, but interventions have often targeted only one or a few causal factors, with limited success. METHODS AND FINDINGS: We assessed the contribution of different pathophysiological mechanisms (red cell production failure [RCPF], haemolysis and blood loss) to severe anaemia in Malawian children in whom etiological factors have been described previously. More complex associations between etiological factors and the mechanisms were explored using structural equation modelling. In 235 children with severe anaemia (haemoglobin<3.2 mMol/L [5.0 g/dl]) studied, RCPF, haemolysis and blood loss were found in 48.1%, 21.7% and 6.9%, respectively. The RCPF figure increased to 86% when a less stringent definition of RCPF was applied. RCPF was the most common mechanism in each of the major etiological subgroups (39.7-59.7%). Multiple aetiologies were common in children with severe anaemia. In the final model, nutritional and infectious factors, including malaria, were directly or indirectly associated with RCPF, but not with haemolysis. CONCLUSION: RCPF was the most common pathway leading to severe anaemia, from a variety of etiological factors, often found in combination. Unlike haemolysis or blood loss, RCPF is a defect that is likely to persist to a significant degree unless all of its contributing aetiologies are corrected. This provides a further explanation for the limited success of the single factor interventions that have commonly been applied to the prevention or treatment of severe anaemia. Our findings underline the need for a package of measures directed against all of the local aetiologies of this often fatal paediatric syndrome

Real-time PCR Demonstrates Ancylostoma duodenale Is a Key Factor in the Etiology of Severe Anemia and Iron Deficiency in Malawian Pre-school Children

Hookworm infections are a major cause of childhood anemia and iron deficiency. Two hookworm species exist of which Ancylostoma duodenale is the less common, yet causing more blood loss than Necator americanus. Although species differentiation and quantification are both of clinical importance, these are often not performed as the technique is complex and laborious using microscopy. Multiplex real-time PCR is a novel diagnostic tool which allows hookworm species differentiation and infection quantification. We applied this test in 830 stool samples of Malawian children with and without severe anemia. The prevalence of hookworm infections was high. A. duodenale was unexpectedly more prevalent than N. americanus. A. duodenale infections were associated with increased risk for severe anemia and iron deficiency, both of which increased with infection load. The study identifies a need for the quantitative screening of species-specific hookworm infections, which readily can be achieved by real-time-PCR. A. duodenale was independently associated with severe anemia and iron deficiency in our study population

Metal-Substituted Microporous Aluminophosphates

This chapter aims to present the zeotypes aluminophosphates (AlPOs) as a complementary alternative to zeolites in the isomorphic incorporation of metal ions within all-inorganic microporous frameworks as well as to discuss didactically the catalytic consequences derived from the distinctive features of both frameworks. It does not intend to be a compilation of either all or the most significant publications involving metal-substituted microporous aluminophosphates. Families of AlPOs and zeolites, which include metal ion-substituted variants, are the dominant microporous materials. Both these systems are widely used as catalysts, in particular through aliovalent metal ions substitution. Here, some general description of the synthesis procedures and characterization techniques of the MeAPOs (metal-contained aluminophosphates) is given along with catalytic properties. Next, some illustrative examples of the catalytic possibilities of MeAPOs as catalysts in the transformation of the organic molecules are given. The oxidation of the hardly activated hydrocarbons has probably been the most successful use of AlPOs doped with the divalent transition metal ions Co2+, Mn2+, and Fe2+, whose incorporation in zeolites is disfavoured. The catalytic role of these MeAPOs is rationalized based on the knowledge acquired from a combination of the most advanced characterization techniques. Finally, the importance of the high specificity of the structure-directing agents employed in the preparation of MeAPOs is discussed taking N,N-methyldicyclohexylamine in the synthesis of AFI-structured materials as a driving force. It is shown how such a high specificity could be predicted and how it can open great possibilities in the control of parameters as critical in catalysis as crystal size, inter-and intracrystalline mesoporosity, acidity, redox properties, incorporation of a great variety of heteroatom ions or final environment of the metal site (surrounding it by either P or Al)

Assessment of the quality of measures of child oral health-related quality of life

Background Several measures of oral health-related quality of life have been developed for children. The most frequently used are the Child Perceptions Questionnaire (CPQ), the Child Oral Impacts on Daily Performances (C-OIDP) and the Child Oral Health Impact Profile (COHIP). The aim of this study was to assess the methodological quality of the development and testing of these three measures. Methods A systematic search strategy was used to identify eligible studies published up to December 2012, using both MEDLINE and Web of Science. Titles and abstracts were read independently by two investigators and full papers retrieved where the inclusion criteria were met. Data were extracted by two teams of two investigators using a piloted protocol. The data were used to describe the development of the measures and their use against existing criteria. The methodological quality and measurement properties of the measures were assessed using standards proposed by the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) group. Results The search strategy yielded 653 papers, of which 417 were duplicates. Following analysis of the abstracts, 119 papers met the inclusion criteria. The majority of papers reported cross-sectional studies (n = 117) with three of longitudinal design. Fifteen studies which had used the original version of the measures in their original language were included in the COSMIN analysis. The most frequently used measure was the CPQ. Reliability and construct validity appear to be adequate for all three measures. Children were not fully involved in item generation which may compromise their content validity. Internal consistency was measured using classic test theory with no evidence of modern psychometric techniques being used to test unidimensionality of the measures included in the COSMIN analysis. Conclusion The three measures evaluated appear to be able to discriminate between groups. CPQ has been most widely tested and several versions are available. COHIP employed a rigorous development strategy but has been tested in fewer populations. C-OIDP is shorter and has been used successfully in epidemiological studies. Further testing using modern psychometric techniques such as item response theory is recommended. Future developments should also focus on the development of measures which can evaluate longitudinal change