Prediction of outcome in adults with severe falciparum malaria: a new scoring system

BACKGROUND: Mortality of falciparum malaria is related to the presence of severe complications. However, no scoring system is available to predict outcome of these patients. The aim of this paper was to devise a simple and reliable malaria prognosis score (MPS) to predict the outcome of adults with severe malaria. METHODS: All slide-positive severe falciparum malaria patients admitted to Ispat General Hospital were studied. Eight clinical parameters that may potentially differentiate or influence the outcome were identified to predict recovery or death RESULTS: Of 248 severe malaria cases, 35 died. There were 212 adults (34 deaths) and 36 children (one death). The malaria score for adults was (MSA) = 1(severe anaemia) + 2 (acute renal failure) + 3(Respiratory distress) +4 (cerebral malaria). The MSA ranges from 0 to 10. The mortality was 2% for MSA 0 – 2; 10% for MSA 3–4, 40% for MSA 5–6 and 90% for MSA 7 or more. The sensitivity is 89.9% and positive predictive value is 94.1% when 5 is taken as the cut off value. CONCLUSION: MSA is a simple and sensitive predictor. It can be administered rapidly and repeatedly to prognosticate the outcome of severe malaria in adults. It can help the treating doctor to assess the patient as well as to communicate to the relatives of the patients about prognosis. The score needs revalidation in other geographical areas

Investigating the Pathogenesis of Severe Malaria: A Multidisciplinary and Cross-Geographical Approach.

More than a century after the discovery of Plasmodium spp. parasites, the pathogenesis of severe malaria is still not well understood. The majority of malaria cases are caused by Plasmodium falciparum and Plasmodium vivax, which differ in virulence, red blood cell tropism, cytoadhesion of infected erythrocytes, and dormant liver hypnozoite stages. Cerebral malaria coma is one of the most severe manifestations of P. falciparum infection. Insights into its complex pathophysiology are emerging through a combination of autopsy, neuroimaging, parasite binding, and endothelial characterizations. Nevertheless, important questions remain regarding why some patients develop life-threatening conditions while the majority of P. falciparum-infected individuals do not, and why clinical presentations differ between children and adults. For P. vivax, there is renewed recognition of severe malaria, but an understanding of the factors influencing disease severity is limited and remains an important research topic. Shedding light on the underlying disease mechanisms will be necessary to implement effective diagnostic tools for identifying and classifying severe malaria syndromes and developing new therapeutic approaches for severe disease. This review highlights progress and outstanding questions in severe malaria pathophysiology and summarizes key areas of pathogenesis research within the International Centers of Excellence for Malaria Research program

Magnetic resonance imaging during life: the key to unlock cerebral malaria pathogenesis?

Understanding the mechanisms underlying the pathophysiology of cerebral malaria in patients with Plasmodium falciparum infection is necessary to implement new curative interventions. While autopsy-based studies shed some light on several pathological events that are believed to be crucial in the development of this neurologic syndrome, their investigative potential is limited and has not allowed the identification of causes of death in patients who succumb to it. This can only be achieved by comparing features between patients who die from cerebral malaria and those who survive. In this review, several alternative approaches recently developed to facilitate the comparison of specific parameters between fatal, non-fatal cerebral malaria and uncomplicated malaria patients are described, as well as their limitations. The emergence of neuroimaging as a revolutionary tool in identifying critical structural and functional modifications of the brain during cerebral malaria is discussed and highly promising areas of clinical research using magnetic resonance imaging are highlighted

Variations in host genes encoding adhesion molecules and susceptibility to falciparum malaria in India

<p>Abstract</p> <p>Background</p> <p>Host adhesion molecules play a significant role in the pathogenesis of <it>Plasmodium falciparum </it>malaria and changes in their structure or levels in individuals can influence the outcome of infection. The aim of this study was to investigate the association of SNPs of three adhesion molecule genes, <it>ICAM1</it>, <it>PECAM1 </it>and <it>CD36</it>, with severity of falciparum malaria in a malaria-endemic and a non-endemic region of India.</p> <p>Methods</p> <p>The frequency distribution of seven selected SNPs of <it>ICAM1</it>, <it>PECAM1 </it>and <it>CD36 </it>was determined in 552 individuals drawn from 24 populations across India. SNP-disease association was analysed in a case-control study format. Genotyping of the population panel was performed by Sequenom mass spectroscopy and patient/control samples were genotyped by SNaPshot method. Haplotypes and linkage disequilibrium (LD) plots were generated using PHASE and Haploview, respectively. Odds-ratio (OR) for risk assessment was estimated using EpiInfo™ version 3.4.</p> <p>Results</p> <p>Association of the ICAM1 rs5498 (exon 6) G allele and the CD36 exon 1a A allele with increased risk of severe malaria was observed (severe versus control, OR = 1.91 and 2.66, P = 0.02 and 0.0012, respectively). The CD36 rs1334512 (-53) T allele as well as the TT genotype associated with protection from severe disease (severe versus control, TT versus GG, OR = 0.37, P = 0.004). Interestingly, a SNP of the <it>PECAM1 </it>gene (rs668, exon 3, C/G) with low minor allele frequency in populations of the endemic region compared to the non-endemic region exhibited differential association with disease in these regions; the G allele was a risk factor for malaria in the endemic region, but exhibited significant association with protection from disease in the non-endemic region.</p> <p>Conclusion</p> <p>The data highlights the significance of variations in the <it>ICAM1</it>, <it>PECAM1 </it>and <it>CD36 </it>genes in the manifestation of falciparum malaria in India. The <it>PECAM1 </it>exon 3 SNP exhibits altered association with disease in the endemic and non-endemic region.</p

The clinical implications of thrombocytopenia in adults with severe falciparum malaria: a retrospective analysis

BackgroundThrombocytopenia is a common finding in adults with severe falciparum malaria, but its clinical and prognostic utility is incompletely defined.MethodsClinical and laboratory data from 647 adults with severe falciparum malaria were analysed retrospectively to determine the relationship between a patient&rsquo;s platelet count on admission to hospital and their subsequent clinical course.ResultsOn admission, 614 patients (94.9%) were thrombocytopenic (platelet count &lt;150&thinsp;&times;&thinsp;109/L) and 328 (50.7%) had a platelet count &lt;50&thinsp;&times;&thinsp;109/L. The admission platelet count was inversely correlated with parasite biomass (estimated from plasma PfHRP2 concentrations, rs&thinsp;=&thinsp;&minus;0.28, P&thinsp;=&thinsp;0.003), the degree of microvascular sequestration (measured with orthogonal polarizing spectral imaging, rs&thinsp;=&thinsp;&minus;0.31, P&thinsp;=&thinsp;0.001) and disease severity (the number of World Health Organization severity criteria satisfied by the patient, rs&thinsp;=&thinsp;&minus;0.21, P &lt;0.001). Platelet counts were lower on admission in the patients who died (median: 30 (interquartile range 22 to 52)&thinsp;&times;&thinsp;109/L versus 50 (34 to 78)&thinsp;&times;&thinsp;109/L in survivors; P &lt;0.001), but did not predict outcome independently from other established laboratory and clinical prognostic indices. The 39 patients (6%) with profound thrombocytopenia (platelet count &lt;20&thinsp;&times;&thinsp;109/L) were more likely to die (odds ratio: 5.00, 95% confidence interval: 2.56 to 9.75) than patients with higher platelet counts, but these high-risk patients could be identified more rapidly with simple bedside clinical assessment. The admission platelet count did not reliably identify the 50 patients (7.7%) with major bleeding during the study.ConclusionsThrombocytopenia is a marker of disease severity in adults with falciparum malaria, but has limited utility in prognostication, triage and management

Central venous catheter use in severe malaria: time to reconsider the World Health Organization guidelines?

<p>Abstract</p> <p>Background</p> <p>To optimize the fluid status of adult patients with severe malaria, World Health Organization (WHO) guidelines recommend the insertion of a central venous catheter (CVC) and a target central venous pressure (CVP) of 0-5 cmH₂O. However there are few data from clinical trials to support this recommendation.</p> <p>Methods</p> <p>Twenty-eight adult Indian and Bangladeshi patients admitted to the intensive care unit with severe <it>falciparum </it>malaria were enrolled in the study. All patients had a CVC inserted and had regular CVP measurements recorded. The CVP measurements were compared with markers of disease severity, clinical endpoints and volumetric measures derived from transpulmonary thermodilution.</p> <p>Results</p> <p>There was no correlation between the admission CVP and patient outcome (p = 0.67) or disease severity (p = 0.33). There was no correlation between the baseline CVP and the concomitant extravascular lung water (p = 0.62), global end diastolic volume (p = 0.88) or cardiac index (p = 0.44). There was no correlation between the baseline CVP and the likelihood of a patient being fluid responsive (p = 0.37). On the occasions when the CVP was in the WHO target range patients were usually hypovolaemic and often had pulmonary oedema by volumetric measures. Seven of 28 patients suffered a complication of the CVC insertion, although none were fatal.</p> <p>Conclusion</p> <p>The WHO recommendation for the routine insertion of a CVC, and the maintenance of a CVP of 0-5 cmH₂O in adults with severe malaria, should be reconsidered.</p