Changes in optic nerve head blood flow in children with cerebral malaria and acute papilloedema.

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 = -0.49, 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.

Correlation of retinal haemorrhages with brain haemorrhages in children dying of cerebral malaria in Malawi.

Retinal haemorrhages increase in number with severity of Plasmodium falciparum malaria and occur in 35-40% of children with cerebral malaria. We performed clinical retinal examinations and histopathological examinations of retina, and parietal and cerebellar sections of the brains, in 33 children in Malawi who died with cerebral malaria, severe malaria anaemia, or coma of other causes. Haemorrhages were counted in a standardized fashion: the Spearman correlation coefficient between the number of haemorrhages in retina and brain was 0.741 for parietal tissue and 0.703 for cerebellar (P < 0.01 for both). Severity of haemorrhage in the retina correlates well with that in the brain. Retinal examination in cerebral malaria is a useful tool in predicting some of the pathophysiological processes occurring in the brain.

Visual outcomes in children in Malawi following retinopathy of severe malaria.

AIM: To investigate whether retinal changes in children with severe malaria affect visual acuity 1 month after systemic recovery. METHODS: All children with severe malaria admitted to a research ward in Malawi during one malaria season were examined by direct and indirect ophthalmoscopy. Visual acuity was tested in those attending follow up by Cardiff cards, Sheridan-Gardiner single letters, or Snellen chart. RESULTS: 96 (68%) children attended follow up, of whom 83 (86%) had visual acuity measured. Cardiff cards were used in 47 (57%) children, and Sheridan-Gardiner letters or Snellen chart in 29 (35%). There was no significant difference in the mean logMAR visual acuity between groups with or without macular whitening (0.14 versus 0.16, p = 0.55). There was no trend for worse visual acuity with increasing severity of macular whitening (p = 0.52) including patients in whom the fovea was involved (p = 0.32). Six (4.2%) children had cortical blindness after cerebral malaria, and all six had other neurological sequelae. Ophthalmoscopy during the acute illness revealed no abnormalities in four of these children. CONCLUSION: Retinal changes in severe malaria, in particular macular whitening, do not appear to affect visual acuity at 1 month. This supports the hypothesis that retinal whitening is due to reversible intracellular oedema in response to relative hypoxia, caused by sequestered erythrocytes infected by Plasmodium falciparum. Impaired visual functioning after cerebral malaria is not attributable to retinal changes and appears to be a cortical phenomenon.

Causes and outcome of bacterial meningitis in Malawian children.

598 children with bacterial meningitis were admitted to the paediatric wards of the Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi from July 1997 - March 2001. Patients were followed up at 1 and 6 months after hospital discharge when physical, neurological, developmental and hearing assessments were made. The most common causes of pyogenic meningitis were Streptococcus pneumoniae (40%), Haemophilus influenzae type b (28%), Neisseria meningitidis (11%), Salmonella species (5%). There was no growth on culture in 13% of cases. The overall mortality was 31% and 38% were left with significant sequelae. Indicators for a poor prognosis were younger age, lower coma score on admission, bacterial cause, nutritional status and HIV positivity.

The effect of HIV infection on paediatric bacterial meningitis in Blantyre, Malawi.

AIM: To compare presentation, progress, and outcome of acute bacterial meningitis in HIV seropositive and seronegative children. METHODS: A double blind randomised placebo controlled study of the use of dexamethasone as adjuvant therapy in acute bacterial meningitis, in children aged 2 months to 13 years, was carried out from July 1997 to March 2001. A total of 598 children were enrolled, of whom 459 were tested for HIV serostatus. RESULTS: Of the 459 children, 34% were HIV seropositive. Their presentation was similar to HIV seronegative children but more were shocked on arrival at hospital (33/157 v 12/302), and more had a focus of infection (85/157 v 57/302). HIV positive children had a higher incidence of Streptococcus pneumoniae infections (52% v 32%). Sixty four cases relapsed; 67% were in HIV positive patients. The mortality in HIV positive children was 65% compared with 36% in HIV negative children. The number of survivors in each group was similar. Hearing loss was more common in HIV negative than HIV positive children (66.3% v 47.2%). Steroid therapy had no influence on meningitis in HIV positive children, but the mortality in HIV negative children was 61% in children given steroids, and 39% in those who did not receive steroids. CONCLUSION: HIV seropositive children who develop bacterial meningitis have a high mortality and are prone to recurrent disease. There is an urgent need to prevent both primary and recurrent infections.

Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial.

BACKGROUND: Steroids are used as adjuvant treatment in childhood pyogenic meningitis to attenuate host inflammatory responses to bacterial invasion. We aimed to assess the effectiveness of dexamethasone in management of acute bacterial meningitis in a developing country. METHODS: In a double-blind, placebo controlled trial, we included 598 children with pyogenic meningitis who had been admitted to the children's wards of the Queen Elizabeth Central Hospital, Blantyre, Malawi. We did physical, neurological, developmental, and hearing assessments at 1 and 6 months after discharge. The primary outcome was overall death. Secondary outcomes included sequelae, in-hospital deaths, and death after discharge. Analysis was done by intention to treat. FINDINGS: Of the 598 included children, 307 (51%) were assigned to dexamethasone and 295 (49%) to placebo. 338 (40%) of 598 patients had Streptococcus pneumoniae, 170 (28%) Haemophilus influenzae type b, 66 (11%) Neisseria meningitidis, and 29 (5%) Salmonella spp. 78 (13%) patients had no growth on culture. The number of overall deaths was the same in the two treatment groups (relative risk 1.00 [95% CI 0.8-1.25], p=0.93). At final outcome, sequelae were identified in 84 (28%) of children on steroids and in 81 (28%) on placebo (relative risk 0.99 [95% CI 0.78-1.27], p=0.97). The number of children dying in hospital did not differ between groups. INTERPRETATION: Steroids are not an effective adjuvant treatment in children with acute bacterial meningitis in developing countries.