Axonal and astrocyte injury markers in the cerebrospinal fluid of Kenyan children with severe malaria.

A retrospective study of cerebrospinal fluid (CSF) levels of markers of brain parenchymal damage was conducted in Kenyan children with severe falciparum malaria. Two markers were analysed by immunoassays: the microtubule-associated protein tau for degenerated axons and S-100B for astrocytes. The level of tau proteins in the CSF was significantly elevated in children with cerebral malaria compared with either malaria with prostration or malaria with seizures but normal consciousness (p<0.001). Elevated tau was also found to be associated with impaired delivery of oxygen (severe anaemia), severe metabolic acidosis manifesting as respiratory distress (increased respiratory rate and deep acidotic breathing) and at higher parasite densities. Elevated S-100B in children was associated with an increased risk of repeated seizures. This study provides evidence that axonal injury is associated with malaria coma and identifies the potential role of severe anaemia, acidosis and hyperparasitaemia to causing brain parenchymal damage in children with malaria.

Clinical features of Plasmodium vivax malaria.

BACKGROUND: Since its reemergence in 1993, a number of cases of Plasmodium vivax malaria have been reported in Korea. We analyzed the cases of malaria patients living in Chuncheon and its neighboring communities, to characterize its clinical manifestations and laboratory findings, and to identify any differences between our clinical findings and those of previous studies. METHODS: We reviewed the clinical records of cases that were confirmed as malaria by peripheral blood smear at Chuncheon Sacred Heart Hospital from July 1998 to September 2001. RESULTS: Forty-four cases were included in the study. All patients were infected with Plasmodium vivax, and presented with high fever; however, tertian fever developed in only 15 patients (35.7%). A number of cases showed various symptoms, which included headache, abdominal pain, nausea and vomiting. Of the 44 cases identified, 41 (93.2%) developed malaria between June and September. Thrombocytopenia was a prominent finding in 75% of the cases at diagnosis, but resolved during or after therapy. Other laboratory abnormalities such as, anemia, elevated transamines, coagulopathies, and elevated lactose dehydrogenase (LDH) were also noted. Cerebrospinal fluid (CSF) studies were performed in five cases, one of which showed pleocytosis in the CSF. CONCLUSION: We noted only 15 patients (35.7%) with tertian fever; the other patients showed variable fever patterns. Thrombocytopenia was the most prominent laboratory finding. Therefore, we suggest that malaria should be included in the differential diagnosis of febrile diseases with an onset between June to and September, regardless of the pattern of the fever.

Intracranial pressure in African children with cerebral malaria.

Opening lumbar cerebrospinal fluid (CSF) pressure was measured with a paediatric spinal fluid manometer in 26 of 61 Kenyan children (mean age 39 months) with cerebral malaria. In all cases pressure was above normal (mean [SD]22.6 [7.4] cm CSF, range 10.5-36). Clinical features of our patients suggest that intracranial hypertension is important in the pathogenesis of cerebral malaria in children, especially as a cause of death. We suggest that raised intracranial pressure is secondary to increased cerebral blood volume. Lowering intracranial pressure may significantly reduce the mortality and morbidity of cerebral malaria. The potential risks and benefits of lumbar puncture should be considered carefully in patients with suspected cerebral malaria.

C-reactive protein and bacterial meningitis.

We have studied prospectively the C-reactive protein values in the cerebrospinal fluid of 54 patients with bacterial meningitis, tuberculous meningitis, and severe malarial infection and convulsions without infections of the central nervous system. CSF CRP above 1 mg/l was observed in 23 out of 28 patients with bacterial meningitis (sensitivity of 82%). The specificity was 73% at the 1 mg/l level. Five out of 19 patients with severe malarial infection had CSF CRP levels above 1 mg/l. Two patients with TB meningitis were also studied. Both of them had CSF CRP above 1 mg/l. Five patients with febrile convulsions or sepsis without meningitis had CSF CRP below 1 mg/l. It is concluded that CSF CRP would not be used as a useful discriminatory test in areas where malaria and TB meningitis are common.

Function of the blood-cerebrospinal fluid barrier in human cerebral malaria: rejection of the permeability hypothesis.

We tested the hypothesis that cerebral malaria is caused by blood-brain barrier inflammation and cerebral edema. In a group of 157 Thai patients with strictly defined cerebral malaria, cerebrospinal fluid (CSF) opening pressures were normal in 79% and were lower in fatal cases than in survivors (means +/- 1 SD, 144 +/- 58 and 167 +/- 51 mm CSF, respectively, P = 0.051). CSF: serum albumin ratios (X 10(3)) in 39 of them were significantly higher than in 61 British controls (medians 8.5 and 5.5, respectively, P = 0.04), but were no higher in 7 fatal cases. In a group of 12 patients this ratio was not significantly higher during coma than after full recovery (means +/- 1 SD, 9.0 +/- 6.2 and 6.7 +/- 4.2, respectively, P greater than 0.1). CSF alpha 2-macroglobulin concentrations were always normal. CSF : serum 77Br- ratios were elevated in 11/19 comatose cases but fell to normal 4 to 9 days later in 11/11 cases. Dexamethasone treatment had no significant effect on bromide partition. The percentage of an intravenously administered dose of 125I-human serum albumin detectable per ml of CSF 6 hr after intravenous injection was 2.4 +/- 1.3 X 10(-5) in 14 comatose patients and 4.4 +/- 4.0 X 10(-5) in 9 of them during convalescence (P greater than 0.1). These results demonstrate that the blood-CSF barrier is essentially intact in patients with cerebral malaria and give no support to the idea that cerebral edema is the cause of coma.

Cerebrospinal fluid folate activity in patients with Plasmodium falciparum cerebral malaria.

Serum and CSF folate levels were determined simultaneously in 28 patients with P. falciparum cerebral malaria. Both mean values were found to be significantly lower than those of normal subjects reported earlier. Ten (35%) and nine (32%) patients showed low serum and CSF folate respectively. Altogether seven patients had low folate levels in both serum and CSF. After being treated in the hospital for one week, both serum and CSF folate levels increased in nine convalescent subjects. The CSF folate levels were statistically significantly higher than those of the acute malarial stage. These findings indicated that both serum and CSF folate levels were depressed in patients with cerebral malaria and increased after recovery.

Pathophysiological and prognostic significance of cerebrospinal-fluid lactate in cerebral malaria.

Cerebrospinal-fluid (CSF) lactate concentrations were elevated in all but 1 of 45 patients with cerebral malaria. They were significantly higher in patients who died (9.0 +/- 5.3 mmol/l, mean +/- SD) than in survivors (3.4 +/- 1.1 mmol/l, p = 0.0002) and had returned to normal values in each of 9 patients studied after recovery of consciousness. There was a significant negative correlation between CSF lactate and CSF glucose. All 11 patients with CSF lactate concentrations above 6 mmol/l died. CSF lactate is thus an important prognostic indicator in cerebral malaria and these findings suggest that hypoxia contributes to the pathogenesis of this disorder.

[Malaria in children, with special reference to cerebral malaria (author's transl)]. / Malaria bei Kindern unter besonderer Berücksichtigung der Cerebralen Malaria

Those who live in areas where Malaria is endemic, acquire immunity by continuous contact. This immunity cannot be acquired during a short holiday. Children in endemic areas acquire a more severe form of malaria during the period of developing immunity and more often suffer complications like acute hemolytic anemia and, in the case of plasmodium falciparum infection, cerebral malaria. This is a report of 39 cases of cerebral malaria which corresponds to an acute encephslopathy with high temperatures, generalized tonic-clonic spasms and unconsciousness. All children were between 6 months and 5 years old. Cerebral malaria at higher ages is rarely seen in Malawi. But its frequency depends on the intensity of endemic infection and the geographic distribution of the types of malaria. 11 (29%) of the 39 children died. Treatment was with chloroquine against which there was no resistance in East Africa for falciparum infections and with plasmaexpanders. In 1 case permanent neurologic changes a spastic cerebral paresis, were seen. Unconsciousness lasting more than 36 hours appears to be a bad prognostic sign. The CSF is clear and normal except for an occasional rise in protein never higher than 90 mg%.