Adult Cerebral Malaria Research Articles

Adult Cerebral Malaria: Acute and Subacute Imaging Findings, Long-term Clinical Consequences.

Cerebral malaria is an important cause of mortality and neurodisability in endemic regions. We show magnetic resonance imaging (MRI) features suggestive of cytotoxic and vasogenic cerebral edema followed by microhemorrhages in 2 adult UK cases, comparing them with an Indian cohort. Long-term follow-up images correlate ongoing changes with residual functional impairment.

Determinants of brain swelling in pediatric and adult cerebral malaria.

Cerebral malaria (CM) affects children and adults, but brain swelling is more severe in children. To investigate features associated with brain swelling in malaria, we performed blood profiling and brain MRI in a cohort of pediatric and adult patients with CM in Rourkela, India, and compared them with an African pediatric CM cohort in Malawi. We determined that higher plasma Plasmodium falciparum histidine rich protein 2 (PfHRP2) levels and elevated var transcripts that encode for binding to endothelial protein C receptor (EPCR) were linked to CM at both sites. Machine learning models trained on the African pediatric cohort could classify brain swelling in Indian children CM cases but had weaker performance for adult classification, due to overall lower parasite var transcript levels in this age group and more severe thrombocytopenia in Rourkela adults. Subgrouping of patients with CM revealed higher parasite biomass linked to severe thrombocytopenia and higher Group A–EPCR var transcripts in mild thrombocytopenia. Overall, these findings provide evidence that higher parasite biomass and a subset of Group A–EPCR binding variants are common features in children and adult CM cases, despite age differences in brain swelling.

Brain Magnetic Resonance Imaging Reveals Different Courses of Disease in Pediatric and Adult Cerebral Malaria.

BackgroundCerebral malaria is a common presentation of severe Plasmodium falciparum infection and remains an important cause of death in the tropics. Key aspects of its pathogenesis are still incompletely understood, but severe brain swelling identified by magnetic resonance imaging (MRI) was associated with a fatal outcome in African children. In contrast, neuroimaging investigations failed to identify cerebral features associated with fatality in Asian adults. MethodsQuantitative MRI with brain volume assessment and apparent diffusion coefficient (ADC) histogram analyses were performed for the first time in 65 patients with cerebral malaria to compare disease signatures between children and adults from the same cohort, as well as between fatal and nonfatal cases. ResultsWe found an age-dependent decrease in brain swelling during acute cerebral malaria, and brain volumes did not differ between fatal and nonfatal cases across both age groups. In nonfatal disease, reversible, hypoxia-induced cytotoxic edema occurred predominantly in the white matter in children, and in the basal ganglia in adults. In fatal cases, quantitative ADC histogram analyses also demonstrated different end-stage patterns between adults and children: Severe hypoxia, evidenced by global ADC decrease and elevated plasma levels of lipocalin-2 and microRNA-150, was associated with a fatal outcome in adults. In fatal pediatric disease, our results corroborate an increase in brain volume, leading to augmented cerebral pressure, brainstem herniation, and death. ConclusionsOur findings suggest distinct pathogenic patterns in pediatric and adult cerebral malaria with a stronger cytotoxic component in adults, supporting the development of age-specific adjunct therapies.

Plasmodium vivax cerebral malaria in an adult patient in Sudan

BackgroundPlasmodium vivax infection is rising in sub-Saharan Africa, where Plasmodium falciparum is responsible for more than 90% of malaria cases. While P. vivax is identified as a major cause of severe and cerebral malaria in South east Asia, the Pacific and South America, most of the severe and cerebral cases in Africa were attributed to P. falciparum. Cases of severe malaria due to P. vivax are emerging in Africa. A few severe P. vivax cases were reported in Eastern Sudan and they were underestimated due to the lack of accurate diagnosis, low parasitaemia and seldom use of rapid diagnostic tests (RDTs).Case presentationA 60-year-old Sudanese male presented to the Al Kuwaiti hospital in the Sudan capital Khartoum. On admission, the patient was complaining of fever (measured temperature was 38 °C), sweating, chills, vomiting and confusion in the past 2 days prior to his admission. He rapidly deteriorated into a coma state within 48 h of the admission, with significant neck stiffness. He was admitted to the intensive care unit and was suspected of meningitis. Lumbar puncture was not performed since the patient was suffering from spinal cord disc. Brain CT scan was unremarkable. Several biochemical, haematological tests, and blood film for malaria were performed. The results of the laboratory tests were within the normal range except of mild elevation of the total white blood cell count and a significant decrease in the platelets count. Malaria parasites were seen in the blood film with high parasitaemia (quantified as 3 +++). The patient was diagnosed as P. vivax cerebral malaria based on the positive blood film and the amplification of P. vivax specific 499 bp amplicon using Plasmodium multi-species multiplex Polymerase Chain Reaction (PCR). The patient was treated with quinine 10 mg/kg body weight for 10 days followed by primaquine 15 mg/days PO for 2 weeks. The symptoms subsided within 48 h and the patients was cured and released from the hospital.ConclusionsPlasmodium vivax is an emerging cause of cerebral malaria in adults in Sudan and should be considered in the differential diagnosis of cerebral malaria for proper management of patients.

Cerebral vivax Malaria in the Postpartum Period

Cerebral malaria is severe malaria presenting with neurological symptoms, including coma that lasts longer than 30 minutes after a seizure, or it is any impairment of consciousness or convulsions in a patient of malaria with no other causes of coma. Cerebral malaria is generally the result of infection by Plasmodium falciparum, but rarely it is a presenting complication or occurs during the course of P. vivax infection. Here we report a unique case of adult cerebral malaria caused by P. vivax presented by seizures and other variant symptoms. Peripheral blood microscopy, parasite antigen-based assays, plasmodium antibodies showed the presence of P. vivax and absence of P. falciparum. The patient was diagnosed and successfully treated with parenteral quinine followed by primaquine without any sequelae. This case demonstrated that sole Plasmodium vivax could induce severe cerebral injury.

Brain Swelling and Mannitol Therapy in Adult Cerebral Malaria: A Randomized Trial

Coma is a frequent presentation of severe malaria in adults and an important cause of death. The role of cerebral swelling in its pathogenesis, and the possible benefit of intravenous mannitol therapy to treat this, is uncertain. A computed tomographic (CT) scan of the cerebrum and lumbar puncture with measurement of cerebrospinal fluid (CSF) pressure were performed on admission for 126 consecutive adult Indian patients with cerebral malaria. Patients with brain swelling on CT scan were randomized to adjunctive treatment with intravenous mannitol (1.5 g/kg followed by 0.5 g/kg every 8 hours; n = 30) or no adjunctive therapy (n = 31). On CT scan 80 (63%) of 126 patients had cerebral swelling, of whom 36 (29%) had moderate or severe swelling. Extent of brain swelling was not related to coma depth or mortality. CSF pressures were elevated (≥200 mm H(2)O) in 43 (36%) of 120 patients and correlated with CT scan findings (P for trend = .001). Mortality with mannitol therapy was 9 (30%) of 30 versus 4 (13%) of 31 without adjunctive therapy (hazard ratio, 2.4 [95% confidence interval, 0.8-7.3]; P = .11). Median coma recovery time was 90 hours (range, 22-380 hours) with mannitol versus 32 hours (range, 5-168 hours) without (P = .02). Brain swelling on CT scan is a common finding in adult patients with cerebral malaria but is not related to coma depth or survival. Mannitol therapy as adjunctive treatment for brain swelling in adult cerebral malaria prolongs coma duration and may be harmful.

Advances in the management of cerebral malaria in adults

Cerebral malaria continues to be a substantial cause of death and disability worldwide. Although many studies deal with cerebral malaria in children, only very few pertain to adults. Presence of multiorgan failure makes the prognosis poor. Various mechanisms in the pathogenesis of cerebral malaria and the role of adjuvant therapy will be discussed. Artemisinin-based therapies have improved antiparasitic treatment, but in-hospital mortality still remains high, as do neurological sequelae. Several recent studies have given new insights in the pathophysiology of cerebral malaria particularly the role of immune mechanisms in disease progression. Recent findings have identified several potential candidates for adjuvant neuroprotective treatment. Recombinant human erythropoietin has shown beneficial effect in experimental cerebral malaria and will soon enter into large clinical trials. Advances have been made in terms of antiparasitic treatment, but the identification of a well tolerated and effective adjuvant treatment to increase survival and reduce brain damage is still pending. The search for new approaches is a major challenge, not least of which is that mechanisms of malaria pathogenesis remain incompletely understood. The paper reviews newer information on pathogenesis and strategies in the management of cerebral malaria in adults.

Neurological findings and outcome in adult cerebral malaria

The neurological findings of 100 patients of adult cerebral malaria were studied. The commonest neurological feature was symmetrical upper motor neuron lesion as evidenced by exaggerated tendon reflexes and bilateral planter extensor (61%). Twenty two percent had features of meningeal irritation and/or meningism. Abnormal posturing occurred decerebrate rigidity (6%) and decorticate rigidity (4%) with or without opisthotonus, focal neurological deficit was noted in 5% cases. Pupillary size and reaction were normal in 86%, poor in 14%. Corneal reflexes were absent in 4% cases. Fundoscopy showed retinal hemorrhage in 16%, papilloedema is 3% and exudates in 1%. Majority of the patients recovered (80%) without any persistent neurological sequelae at the time of discharge from hospital and death rate was 20%. Patients having focal neurological deficit, disconjugate gaze, poor pupillary reaction, absent corneal reflex and papilloedema were more susceptible to death. Delay in hospitalization and deep coma were also associated with increased mortality, whereas early hospitalization and proper nursing care could reduce mortality.

Cerebral malaria in adults — a description of 526 cases admitted to Ispat General Hospital in Rourkela, India

Although the clinical picture of cerebral malaria in children has been reported extensively, scant information is available about cerebral malaria in adults. This report relates to one of the largest series of adult cases of cerebral malaria patients ever described. At Rourkela, in eastern India, 526 adults (aged >12 years) who each satisfied the World Health Organization's criteria for cerebral malaria were admitted to Ispat General Hospital between 1995 and 2001. These cases represented 18% of the 2994 adult patients who were admitted with Plasmodium falciparum malaria over the same period. Most (76%) of the adult cases of cerebral malaria were male, 48% were aged 21-40 years, and only 4% were older than 60 years. The most common presenting symptoms were fever (97.7%), vomiting (54.6%), headache (30.8%) and seizures (17.1%). Most (62.4%) of the cases had associated severe complications: jaundice (47.5%), acute renal failure (28.9%), and/or severe anaemia (9.7%). Overall, 175 (23%) of the cases were fatal, mortality being particularly high (59%) among those with multi-organ failure. Of the fatal cases, 107 (61%) died within the first 24 h of hospitalization, presumably indicative of late presentation. As the management of multiple complications may be inadequate at primary centres, early referral to higher centres is recommended.

Preferences for hospital quality in Zambia: results from a discrete choice experiment

This study reports on the results of a discrete choice experiment undertaken in Zambia to assess the factors influencing the demand for hospital care in Zambia, in particular the role of (perceived) quality and trade-offs between price and quality. Valuations of quality were evaluated for the treatment of two acute medical conditions, cerebral malaria in adults and acute pneumonia in children. Marginal utilities and willingness-to-pay for attributes of quality of hospital care were estimated, together with the influence of socioeconomic characteristics on these valuations and the extent of non-linearities in valuations of time and money. We find the technical quality of care, as represented by the thoroughness of examination, to be the most important quality attribute, followed by staff attitudes and drug availability. Valuations of examination thoroughness increase with increasing socioeconomic status. The disutility of cost was found to decrease with higher socioeconomic status, as was the value of drug availability. The implications of the findings for Zambian hospital sector reforms are discussed.

Admission diagnosis of cerebral malaria in adults in an endemic area of Tanzania: implications and clinical description.

Cerebral malaria is commonly diagnosed in adults in endemic areas in Africa, both in hospitals and in the community. This presents a paradox inconsistent with the epidemiological understanding that the development of immunity during childhood confers protection against severe disease in adult life. To establish the contribution of Plasmodium falciparum infection in adults admitted with neurological dysfunction in an endemic area, to assess the implications of an admission clinical diagnosis of 'cerebral malaria' on the treatment and clinical outcome, and to describe the clinical features of patients with malaria parasitaemia. Prospective observational study. We studied adult patients admitted with neurological dysfunction to Muhimbili National Hospital, Dar-es-Salaam, Tanzania from October 2000 to July 2001. A full blood count was done and serum creatinine, blood glucose and P. falciparum parasite load were measured. Of 199 patients (median age 34.6 years), 38% were diagnosed as 'cerebral malaria' on admission, but only 7.5% had detectable parasitaemia, giving a positive predictive value of 13.3%. Only 1% fulfilled the WHO criteria for cerebral malaria. The prevalence of parasitaemia (7.5%) was less than that observed in a group of asymptomatic controls (9.3%), but distribution of parasite densities was higher in the patients. Mortality was higher in patients with no parasitaemia (22.3%) than in those with parasitaemia (13%). Cerebral malaria was grossly overdiagnosed, resulting in unnecessary treatment and insufficient investigation of other possible diagnoses, which could lead to higher mortality. Extension of this misperception to the assessment of cause of death in community surveys may lead to an overestimation of the impact of malaria in adults.

Adult cerebral malaria: prognostic importance of imaging findings and correlation with postmortem findings.

To correlate imaging abnormalities, clinical features, and postmortem findings in patients with proved cerebral malaria. Twenty-one patients aged 17-50 years with cerebral malaria consented to undergo transverse nonenhanced (10-mm sections) and contrast material-enhanced (8-mm sections in posterior fossa and 10-mm sections in supratentorial region) CT on admission (n = 21) and on day 10 (n = 6), with thin sections (5 mm) obtained in the area of abnormality. All CT scans were evaluated for diffuse cerebral edema, focal parenchymal abnormalities, and hemorrhage. CT findings were categorized as normal, diffuse cerebral edema, and edema with thalamic hypoattenuation without or with cerebellar hypoattenuation. Spearman rank correlation test was performed. Initial scans were normal in seven patients with mild disease (median Acute Physiology and Chronic Health Evaluation [APACHE] II score of 7, median Glasgow Coma Scale [GCS] score of 10), and all survived. Of eight patients with diffuse cerebral edema (GCS > or = 8; median APACHE II, 21), six survived. Cerebral edema with thalamic and cerebellar white matter hypoattenuation was seen in five patients. All had GCS score of 6 or less, median APACHE II score of 26, and multiorgan failure; none survived. One patient (GCS = 6) had thalamic hypoattenuation without cerebellar lesions. He survived with mild residual hemiparesis. Diffuse petechial hemorrhages were seen in the cerebrum and cerebellum at autopsy in all seven patients who died. These petechial hemorrhages were not visualized on CT scans. CT findings did not correlate with degree of parasitemia. CT findings correlate well with level of consciousness and severity of disease but underestimate the extent of disease at pathologic examination. A normal CT scan indicates a favorable outcome, whereas cerebellar hypoattenuation portends a poor outcome.

Prognostic indicators in adult cerebral malaria: a study in Burundi, an area of high prevalence of HIV infection

We examined the possible risk factors for poor prognostic in cerebral malaria in 31 adults from Burundi, an area of high prevalence rate of HIV-1 infection. Depth of coma, temperature, vomiting, seizures, parasite load, or anaemia did not modify the outcome. High levels of creatinine, bilirubin, and/or lactates were indicators of poor prognostic. HIV-1 infection did not affect the clinical or biological presentation of cerebral malaria, and did not appear to influence the outcome.