Association between measures of vitamin A and the ocular fundus findings in cerebral malaria.

OBJECTIVE: To investigate the relationship between serum vitamin A levels and conjunctival impression cytology and retinal whitening present in Malawian children with cerebral malaria. METHODS: Standard retinal examination and conjunctival impression cytology were performed at hospital admission on 101 consecutively admitted children with cerebral malaria. Blood samples were drawn from 56 children at 24 hours, frozen at -20 degrees C, and transported for assessment of vitamin A levels by high-performance liquid chromatography. Associations among fundus findings and vitamin A measurements were sought. RESULTS: The whitening of the retina that we have previously described in children with cerebral malaria was found to be associated with a mean+/-SD serum vitamin A level of 0.29+/-0.1 micromol/L, compared with a mean vitamin A level of 0.41+/-0.2 micromol/L in children without retinal whitening. Children with retinal whitening were 2.77 (95% CI, 1.06-7.3) times more likely to have abnormal conjunctival impression cytology results than those without whitening. No child had any clinical or ophthalmologic evidence of chronic vitamin A deficiency. CONCLUSIONS: The retinal whitening described in children with cerebral malaria is associated with low serum vitamin A levels and with abnormal conjunctival impression cytology results and may be due to acute vitamin A deficiency at the tissue level.

Retinal findings predictive of outcome in cerebral malaria.

The pathogenesis of cerebral malaria is poorly understood. Direct and indirect ophthalmoscope examinations of 141 Malawian children with strictly defined cerebral malaria revealed 2 distinct and prognostically significant findings: papilloedema and extramacular retinal oedema. The relative risk of death in patients with papilloedema was 6.7 times that in patients without papilloedema. Extramacular retinal oedema was associated with a 2.9 fold increase in the relative risk of dying. The mortality rate in patients with neither of these signs was only 1.3% compared to an overall mortality rate of 9.2%. The clinical and laboratory features associated with each of these ophthalmological findings were different, suggesting that there may be at least 2 different pathogenetic processes in patients with cerebral malaria.

Ocular fundus findings in Malawian children with cerebral malaria.

BACKGROUND: Cerebral malaria is a major cause of mortality and morbidity in children in tropical regions. The pathogenesis of this important complication of Plasmodium falciparum infection is not well understood. A number of observers have commented on the presence of retinal pathology in various types of malaria. Previous reports have not demonstrated that fundus findings are significantly associated with outcome. METHODS: The authors examined the ocular fundi, by direct and indirect ophthalmoscopy, of 56 children admitted consecutively with cerebral malaria. RESULTS: Every child with a normal fundus on admission recovered fully, but two conditions were found to be associated with a poor outcome. Patients with papilledema had a relative risk of poor outcome 5.2 times greater than those without this finding (P < 0.01). Patients with retinal edema outside the posterior vascular arcades had a relative risk of poor outcome 3.9 times greater than those without this finding (P < 0.01). These two fundus findings were independently predictive of a poor outcome. CONCLUSION: Fundus findings are useful as predictors of outcome in children with cerebral malaria. The authors' findings suggest that there may be two distinct mechanisms associated with poor outcome in these children.

Intramuscular artemether vs intravenous quinine: an open, randomized trial in Malawian children with cerebral malaria.

OBJECTIVES: To compare artemether (by intramuscular injection) and quinine (by intravenous infusion) as treatments for cerebral malaria in African children. METHODS: An open, randomized trial conducted at the Queen Elizabeth Central Hospital in Blantyre, Malawi. This trial was part of a multicentre study designed to determine if treatment with artemether would significantly lower mortality rates compared with quinine. Data from 83 artemether recipients and 81 quinine recipients are reported here. RESULTS: Overall mortality rates and coma resolution times were not significantly different in the two treatment groups. Parasite and fever clearance times were significantly more rapid in the artemether recipients. Analyses which took into account the possible confounding variables did not significantly alter the findings of these unadjusted analyses. CONCLUSION: These results do not suggest that treatment with artemether would confer a survival advantage in children with life-threatening malaria. The power and precision of the estimated treatment effects of artemether would be enhanced by a meta-analysis of all relevant clinical trials.

Rapid coma resolution with artemether in Malawian children with cerebral malaria.

Artemisinin compounds clear parasitaemia more rapidly than other drugs do in both mild and severe malaria, but no advantage in clinical efficacy has been shown. We have compared artemether treatment with standard quinine treatment in Malawian children with cerebral malaria. 65 unconscious children were randomly allocated to intravenous quinine (n = 37) or intramuscular artemether (n = 28) treatment. The two groups were well matched for various prognostic features. Median parasite clearance times were shorter in the artemether group (28 [interquartile range 18-34] vs 40 [36-44] h in the quinine group, p = 0.0002). Coma resolution times were also shorter with artemether than with quinine (8 [4-15] vs 14 [10-36] h, p = 0.01).

PIP: The antimalarials artemether and quinine were compared in 65 unconscious children with cerebral malaria treated from January to June 1992 at Queen Elizabeth Central Hospital, Blantyre, Malawi. Artemether is a derivative of the Chinese traditional remedy ginghaosu, and is chemically unrelated to quinine or other existing antimalarials. These patients had a coma score of 2 or less, peripheral Plasmodium falciparum parasitemia, and no other cause of fever or altered consciousness. They were randomized to be treated with either intravenous quinine dihydrochloride 20 mg/kg over 4 hours (37 children), then 10 mg/kg over 2 hours every 8 hours until the patient was able to drink, or artemether in in oil suspension (Rhone-Poulenc-Rorer, France) 3.2 mg/kg (28 children), then 1.6 mg/kg daily. Both groups received at least 3 doses of the drug until parasite clearance (2 consecutive 4-hourly negative screens) or recovery of consciousness. Then each received a dose of fansidar (pyrimethamine/sulphadoxine). Both parasite clearance time and time to regain consciousness (coma score of 5) were more rapid in the artemether group. Coma resolved in 8 hours in the artemether group and 14 hours in the quinine group. Outcome in terms of fever resolution time, neurological sequelae, and mortality did not differ between groups. The study was too small to compare survival: this is part of a multicenter trial to study the effect of artemether vs. quinine on mortality.

Melioidosis in Southern Vietnam: clinical surveillance and environmental sampling.

From 1992-1998, Burkholderia pseudomallei was isolated from only 9 (0.25%) of 3653 cultures of blood from febrile patients admitted to the Centre for Tropical Diseases in Ho Chi Minh City, an infectious disease referral center for southern Vietnam. Soil was sampled from 407 sites in 147 rice fields along the 5 major roads radiating from Ho Chi Minh City. B. pseudomallei was isolated from 73 sites (18%) in 39 rice fields (27%), but only 15 (21%) of the 71 isolates from 9 (6%) of 147 fields were the virulent l-arabinose (ara)-negative biotype. All except 1 of the fields with the ara-negative biotype were close to the homes of the patients with melioidosis. The low incidence of melioidosis in the provinces around Ho Chi Minh City may be explained by the restricted distribution of ara-negative B. pseudomallei in the soil in this area.