BackgroundA procoagulant state is implicated in cerebral malaria (CM) pathogenesis, but whether disseminated intravascular coagulation (DIC) is present or associated with a fatal outcome is unclear.ObjectivesTo determine the frequency of overt DIC, according to ISTH criteria, in children with fatal and non-fatal CM.Methods/patientsMalawian children were recruited into a prospective cohort study in the following diagnostic groups: retinopathy-positive CM (n=140), retinopathy-negative CM (n=36), non-malarial coma (n=14), uncomplicated malaria (UM), (n=91), mild non-malarial febrile illness (n=85), and healthy controls (n=36). Assays in the ISTH DIC criteria were performed, and three fibrin-related markers, i.e. proteinC, antithrombin, and soluble thrombomodulin, were measured.Results and conclusionsData enabling assignment of the presence or absence of overt DIC' were available for 98 of 140 children with retinopathy-positive CM. Overt DIC was present in 19 (19%), and was associated with a fatal outcome (odds ratio [OR]3.068; 95% confidence interval [CI]1.085-8.609; P=0.035]. The levels of the three fibrin-related markers and soluble thrombomodulin were higher in CM patients than in UM patients (all P< 0.001). The mean fibrin degradation product level was higher in fatal CM patients (71.3gmL(-1) [95% CI49.0-93.6]) than in non-fatal CM patients (48.0 gmL(-1) [95%CI37.7-58.2]; P=0.032), but, in multivariate logistic regression, thrombomodulin was the only coagulation-related marker that was independently associated with a fatal outcome (OR1.084 for each ng mL(-1) increase [95% CI1.017-1.156]; P= 0.014). Despite these laboratory derangements, no child in the study had clinically evident bleeding or thrombosis. An overt DIC score and high thrombomodulin levels are associated with a fatal outcome in CM, but infrequently indicate a consumptive coagulopathy.

Introduction Malaria is a major public health problem in terms of both morbidity and mortality. Due to severe health economic costs of malaria, there is a need for methods that will help to understand the geographical variation of the disease risk and its association with climate. This paper analyses the variation of hospital diagnosed malaria incidences in relation to Rainfall, Temperatures and Humidity that are measured at district level from 2002 to 2010 in Malawi. Methods Using district hospital and health facilities malaria case records and climatic factors, a non-parametric regression model based on generalized additive mixed models (GAMM) was developed. Modeling and inference is within full Bayesian framework through Markov Chain Monte Carlo (MCMC) simulation techniques. Results There is a decreasing trend of malaria incidences in the study period and an evidence of spatial variation in the risk of having malaria which is higher in Warm Wet Season (November to March) with RR = 1.07, 95% CI = [1.02-1.07] mainly in districts along lakes and rivers such as Rumphi, NkhataBay, Nkhotakota, Salima, Ntcheu, Balaka, Mwanza, Chikhwawa and Nsanje. Marginal changes in environmental factors greatly affect the risk of increased malaria incidences. Malaria incidences in a given month are strongly positively associated with minimum temperatures of around 20 degree Celsius the previous month. Conclusions and Recommendations Modeling the impact of known factors alone is not sufficient to produce a satisfactory fit to the observations, geographical variation needs to be considered to improve the fit and account for heterogeneity. Ignoring a nonlinear relationship may result in misleading estimates of residual spatial surface which would have been overlooked by a parametric linear model. Association between weather and malaria should be considered in the development and implementation of malaria interventions. History of Malaria Testing Among Out-Patient Adults Receiving Antimalarial Drugs at Queen Elizabeth Central Hospital (QECH), Southern Malawi, 2012 A.Kamoto1, A S. Muula2 1.Fourth Year Student, Department of Pharmacy, University Of Malawi, College Of Medicine, Blantyre Malawi. Email: akamoto@medcol.mw 2.Department of Community Health, University of Malawi, College Of Medicine, Blantyre Malawi

To collect normative MRI data for effective clinical and research applications. Such data may also offer insights into common neurological insults.

BACKGROUND AND PURPOSE: There have been few neuroimaging studies of pediatric CM, a common often fatal tropical condition. We undertook a prospective study of pediatric CM to better characterize the MRI features of this syndrome, comparing findings in children meeting a stringent definition of CM with those in a control group who were infected with malaria but who were likely to have a nonmalarial cause of coma.MATERIALS AND METHODS: Consecutive children admitted with traditionally defined CM (parasitemia, coma, and no other coma etiology evident) were eligible for this study. The presence or absence of malaria retinopathy was determined. MRI findings in children with ret+ CM (patients) were compared with those with ret- CM (controls). Two radiologists blinded to retinopathy status jointly developed a scoring procedure for image interpretation and provided independent reviews. MRI findings were compared between patients with and without retinopathy, to assess the specificity of changes for patients with very strictly defined CM.RESULTS: Of 152 children with clinically defined CM, 120 were ret+, and 32 were ret-. Abnormalities much more common in the patients with ret+ CM were markedly increased brain volume; abnormal T2 signal intensity; and DWI abnormalities in the cortical, deep gray, and white matter structures. Focal abnormalities rarely respected arterial vascular distributions. Most of the findings in the more clinically heterogeneous ret- group were normal, and none of the abnormalities noted were more prevalent in controls.CONCLUSIONS: Distinctive MRI findings present in patients meeting a stringent definition of CM may offer insights into disease pathogenesis and treatment.

Evidence from autopsy and in vitro binding studies suggests that adhesion of erythrocytes infected with Plasmodium falciparum to the human host intercellular adhesion molecule (ICAM)-1 receptor is important in the pathogenesis of severe malaria. Previous association studies between polymorphisms in the ICAM1 gene and susceptibility to severe malarial phenotypes have been inconclusive and often contradictory. We performed genetic association studies with 15 single nucleotide polymorphisms (SNPs) around the ICAM1 locus. All SNPs were screened in a family study of 1071 trios from The Gambia, Malawi and Kenya. Two key non-synonymous SNPs with previously reported associations, rs5491 (K56M or ‘ICAM-1Kilifi’) and rs5498 (K469E), were tested in an additional 708 Gambian trios and a case-control study of 4058 individuals. None of the polymorphisms were associated with severe malaria phenotypes. Pooled results across our studies for ICAM-1Kilifi were, in severe malaria, odds ratio (OR) 1.02, 95% confidence interval (CI) 0.96–1.09, P=0.54, and cerebral malaria OR 1.07, CI 0.97–1.17, P=0.17. We assess the available epidemiological, population genetic and functional evidence that links ICAM-1Kilifi to severe malaria susceptibility.

Objective: To investigate capillary blood flow in the optic nerve head ( ONH) of children with cerebral malaria.Methods: Malawian children with cerebral malaria admitted to a paediatric research ward were examined by direct and indirect ophthalmoscopy. ONH blood flow was measured using laser Doppler flowmetry (LDF) in suitable patients. Mean blood volume and velocity were obtained from 30 to 60 s recordings from the temporal ONH and used to calculate blood flow. These were compared with admission variables, funduscopic findings and disease outcomes.Results: 45 children with cerebral malaria had LDF recordings; 6 subsequently died and 5 survivors had neurological sequelae. 12 (27%) had papilloedema. The mean microvascular blood volume was higher in patients with papilloedema (3.28 v 2.54 arbitrary units, p = 0.002). The blood velocity correlated directly with haematocrit (r = 0.46, p = 0.001) and inversely with blood glucose (r = 20.49, p = 0.001).Conclusion: The increase in ONH microvascular blood volume in papilloedema measured by LDF is consistent with current theories of pathogenesis of papilloedema. LDF has potential as a tool to distinguish papilloedema from pseudopapilloedematous disc swellings. The relationship between blood velocity and haematocrit may relate to levels of sequestration in cerebral malaria.

Objectives: Computers are widely used for data management in clinical trials in the developed countries, unlike in developing countries. Dependable systems are vital for data management, and medical decision making in clinical research. Monitoring and evaluation of data management is critical. In this paper we describe database structures and procedures of systems used to implement, coordinate, and sustain data management in Africa. We outline major lessons, challenges and successes achieved, and recommendations to improve medical informatics application in biomedical research in sub-Saharan Africa.Methods: A consortium of experienced research units at five sites in Africa in studying children with disease formed a new clinical trials network, Severe Malaria in African Children. In December 2000, the network introduced on observational study involving these hospital-based sites. After prototyping, relational database management systems were implemented for data entry and verification, data submission and quality assurance monitoring.Results: Between 2000 and 2005, 25,858 patients were enrolled. Failure to meet data submission deadline and data entry errors correlated positively (correlation coefficient, r = 0.82), with more errors occuring when data was submitted late. Data submission lateness correlated inversely with hospital admissions (r = -0.62).Conclusions: Developing and sustaining dependable DBMS, ongoing modifications to optimize data management is crucial for clinical studies. Monitoring and communication systems are vital in multi-center networks for good data management. Data timeliness is associated with data quality and hospital admissions.

Ocular fundus pathology in Plasmodium falciparum malaria is common and has prognostic significance. We have made a collaborative effort to document the ocular features in several populations. Based on examination of 735 patients in Malawi, Kenya and The Gambia by direct and indirect ophthalmoscopy with dilated pupils, we have determined that the 5 distinct clinical features (in order of frequency) include retinal whitening, haemorrhages, unique vessel abnormalities, papilloedema, and cotton wool spots. Photographs and descriptions of these are presented, along with a proposed grading scheme.

Children living in sub-Saharan Africa bear the brunt of the mortality from falciparum malaria, yet there is a dearth of relevant post-mortem data. Clinical studies from centers in Africa suggest that the pathophysiology of severe malaria is different in children and adults. Three overlapping clinical syndromes, metabolic acidosis manifesting as hyperpnea, cerebral malaria, and severe anemia, are responsible for nearly all the deaths in African children. Despite improvements in antimalarial treatment, there has not been a significant reduction in mortality. We review the pathology and pathophysiology of fatal falciparum malaria in African children. Many questions remain, the answers to which would facilitate the development and evaluation of new approaches to the management of this disease.

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