clinical Clinical opinions hypertension, left ventricular function, age, diabetes and history of previous stroke.1 Following this, the patient’s potential benefit from antiplatelet therapy and OAC should be estimated. Finally, and perhaps most tricky, the patient’s risk of major bleeding should be assessed. Future research should try to develop more robust methods to predict the individual risk of stroke and major bleeding. Reference 1 Gage BF, Waterman AD, Shannon W et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001; 285:2864–70. Severe anaemia in sub-Saharan Africa T Latham VSO Visiting Lecturer in Haematology, College of Medicine, Blantyre, Malawi, and Honorary Clinical Senior Lecturer, University of Edinburgh, UK TITLE Severe anemia in Malawian children Published online September 2009 Authors Calis JCJ, Phiri KS, Faragher EB et al. Correspondence to T Latham, Department of Haematology, College of Medicine, Private Bag 360, Chichiri, Blantyre, Malawi Journal N Engl J Med 2008; 358:888–99. Declaration of Interests No conflict of interests declared. Kanthu n’kavumbu, kavumbula mende pachisa (Something is revealed, stirring up the rat in the nest) – Malawian (Chewa) idiom Summary In one of the most comprehensive studies published to date of the aetiology of severe anaemia in the developing world, Calis et al. compare the prevalence of factors associated with severe anaemia in 382 children aged between six and 60 months of age with haemoglobin (Hb) <5.0 g/dL, and 759 apparently healthy matched controls. Subjects were recruited from an urban teaching hospital in Malawi and a rural district hospital. Two groups of control patients, one from the community and one consisting of surgical outpatients, were studied. The control group data illustrate the public health importance of anaemia and its causes, and the difficulty of inferring causation from uncontrolled studies in populations with widespread poor health. Even among the community control groups, the mean Hb was 9.9g/ dL. Deficiencies of iron, vitamin B12, vitamin A and generalised malnutrition as suggested by wasting were common in the control group as a whole (69.4%, 15.6%, 65.6% and 6.2% respectively); folate deficiency was not found. Infective causes were also very prevalent (malaria [Plasmodium falciparum] 42.8%, human immunodeficiency virus [HIV] 6%, hookworm 1.9%, Epstein-Barr virus [EBV] 18%). Haemoglobinopathies were rare (Hb S/S 1.0%; b thalassaemia and a0 thalassaemias have not been 232 tel. +265 995629062 e-mail tom.latham@ed.ac.uk described in Malawi), although the prevalence of glucose6-phosphate dehydrogenase (G6PD) deficiency was 9%. Factors positively associated with severe anaemia in a multivariate analysis were deficiencies of vitamins A and B12, infection with HIV, EBV, P. falciparum and hookworm, bacteraemia (most commonly with non-typhi Salmonella species), and G6PD deficiency. Low maternal education levels were also associated with severe anaemia. Counterintuitively, iron deficiency was less common among children with severe anaemia than in the control group, especially for children from an urban area. The authors note an inverse association between bacteraemia and iron deficiency and suggest that a protective role of iron deficiency against bacteraemia may have a net effect of protecting against severe anaemia. A subsequent follow-up of patients in the study1 showed an in-hospital mortality of 6.4% and an 18-month allcause mortality of 12.6%. This compares with a 1.4% all-cause mortality for the community controls (which is distressingly high in itself). HIV infection was the strongest predictor of subsequent mortality in patients with severe anaemia. Opinion One of the first observations that strikes any doctor working in the developing world is the frequency and severity of anaemia both in hospital patients and the community. Based on World Health Organization criteria J R Coll Physicians Edinb 2009; 39:232–3 © 2009 RCPE Clinical opinions This study highlights the multifactorial nature of severe anaemia and explains why the results of intervention trials targeting specific factors, which have shown efficacy in reducing community levels of anaemia,6,7 cannot be generalised to patients with severe anaemia. What is desperately needed in resource-poor environments where investigation facilities are extremely limited (in Malawi even a full blood count is available only in referral centres) is an evidence base on which to base empirical treatment strategies. While the results are not necessarily generalisable to other environments, this study is a major contribution to such an evidence base and suggests many options for the management of patients with severe anaemia which may not have been widely appreciated, in particular the importance of bacterial sepsis and the need for caution in treating patients with suspected sepsis with iron. While such a broad-based study will be difficult to replicate in other environments, outcome studies of empirical treatment protocols incorporating treatment of the most important associations of severe anaemia described in this study are feasible and would not need large numbers to provide a sounder evidence base for treatment. References 1 2 3 4 Phiri KS, Calis JC, Faragher B et al. Long term outcome of severe anaemia in Malawian children. PLoS One 2008; 3:e2903. De Benoist B, McLean E, Egli I et al., editors. Worldwide prevalence of anaemia1998–2005: WHO global database on anaemia. Geneva: World Health Organization; 2008. Available from: http://whqlibdoc. who.int/publications/2008/9789241596657_eng.pdf English M, Ahmed M, Ngando C et al. Blood transfusion for severe anaemia in children in a Kenyan hospital. Lancet 2002; 359:494–5. Newton CR, Warn PA, Winstanley PA et al. Severe anaemia in children living in a malaria endemic area of Kenya. Trop Med Int Health 1997; 2:165–78. 5 6 7 Lewis DK, Whitty CJ, Walsh AL et al. Treatable factors associated with severe anaemia in adults admitted to medical wards in Blantyre, Malawi, an area of high HIV seroprevalence. Trans R Soc Trop Med Hyg 2005; 99:561–7. Massaga JJ, Kitua AY, Lemnge MM et al. Effect of intermittent treatment with amodiaquine on anaemia and malarial fevers in infants in Tanzania: a randomised placebo-controlled trial. Lancet 2003; 361:1853–60. Verhoef H, West CE, Nzyuko SM et al. Intermittent administration of iron and sulfadoxine-pyrimethamine to control anaemia in Kenyan children: a randomised controlled trial. Lancet 2002; 360: 908–14. Erratum in: Lancet 2002; 360:1256. Microalbuminuria in childhood diabetes K Matyka Senior Lecturer in Paediatrics,,Clinical Sciences Research Institute, University Hospital, Coventry, UK TITLE Risk of microalbuminuria and progression to macroalbuminuria in a cohort with childhood onset type 1 diabetes: prospective observational study AUTHORS Amin R, Widmer B, Prevost AT et al. JOURNAL BMJ 2008; 336:697–701. Declaration of Interests No conflict of interests declared. Published online September 2009 Correspondence to K Matyka, Clinical Sciences Research Institute, Clinical Sciences Building, University Hospital – Walsgrave Campus, Clifford Bridge Road, Coventry CV2 2DX, UK tel. +44 (0)24 7696 8586 e-mail k.a.matyka@warwick.ac.uk Summary The Oxford Regional Prospective Study (ORPS) was initiated in 1986 to examine the development of early nephropathy in a large cohort of children aged less than 16 years followed from diagnosis with type 1 diabetes. The most recent paper from this study presents data from more than 500 participants with a mean age of 8.8 years at diagnosis and followed up for an average of 9.8 years. Children and young people had annual assessments of diabetes control using glycated haemoglobin, yearly J R Coll Physicians Edinb 2009; 39:233–5 © 2009 RCPE View publication stats lipid and blood pressure measurement and collection of three early morning urine samples for their albumin/ creatinine ratio. The results suggest that the cumulative prevalence of microalbuminuria (MA) in this group of young people was 26.7% after 10 years of diabetes and 50.7% after 19 years of diabetes, with a mean age of onset of MA of 16.1 years. Microalbuminuria was more common in girls, but the only predictor of the development of MA was long-term diabetes control as assessed by glycated haemoglobin 233 clinical (Hb <11.0 g/dL), it is thought that about two thirds of people in Africa and south Asia are anaemic.2 In hospital practice, severe anaemia (variably defined as Hb <4.0– 6.0 g/dL) is a great contributor to workload; 12–19% of children admitted to hospital in sub-Saharan Africa are severely anaemic3,4 and anaemia is thought to contribute to approximately 10% of adult inpatient deaths.5