Safety of lumbar puncture in comatose children with clinical features of cerebral malaria

Objective: We assessed the independent association of lumbar puncture (LP) and death in Malawian children admitted to the hospital with the clinical features of cerebral malaria (CM). Methods: This was a retrospective cohort study in Malawian children with clinical features of CM. Allocation to LP was nonrandom and was associated with severity of illness. Propensity score-based analyses were used to adjust for this bias and assess the independent association between LP and mortality. Results: Data were available for 1,075 children: 866 (80.6%) underwent LP and 209 (19.4%) did not. Unadjusted mortality rates were lower in children who underwent LP (15.3% vs 26.7% in the no-LP group) but differences in covariates between the 2 groups suggested bias in LP allocation. After propensity score matching, all covariates were balanced. Propensity score-based analyses showed no change in mortality rate associated with LP: by inverse probability weighting, the average risk reduction was 2.0% at 12 hours (95% confidence interval -1.5% to 5.5%, p = 0.27) and 1.7% during hospital admission (95% confidence interval -4.5% to 7.9%, p = 0.60). Undergoing LP did not change the risk of mortality in subanalyses of children with severe brain swelling on MRI or in those with papilledema. Conclusion: In comatose children with suspected CM who were clinically stable, we found no evidence that LP increases mortality, even in children with objective signs of raised intracranial pressur

Central Nervous System Virus Infection in African Children with Cerebral Malaria

We aimed to identify the contribution of central nervous system (CNS) viral coinfection to illness in African children with retinopathy-negative or retinopathy-positive cerebral malaria (CM). We collected cerebrospinal fluid (CSF) from 272 children with retinopathy-negative or retinopathy-positive CM and selected CSF from 111 of these children (38 retinopathy positive, 71 retinopathy negative, 2 retinopathy unknown) for analysis by metagenomic next-generation sequencing. We found CSF viral coinfections in 7/38 (18.4%) retinopathy-positive children and in 18/71 (25.4%) retinopathy-negative children. Excluding HIV-1, human herpesviruses (HHV) represented 61% of viruses identified. Excluding HIV-1, CNS viral coinfection was equally likely in children who were retinopathy positive and retinopathy negative (P = 0.1431). Neither mortality nor neurological morbidity was associated with the presence of virus (odds ratio [OR] = 0.276, 95% CI: 0.056-1.363). Retinopathy-negative children with a higher temperature, lower white blood cell count, or being dehydrated were more likely to have viral coinfection. Level of consciousness at admission was not associated with CNS viral coinfection in retinopathy-negative children. Viral CNS coinfection is unlikely to contribute to coma in children with CM. The herpesviruses other than herpes simplex virus may represent incidental bystanders in CM, reactivating during acute malaria infection

The interaction of malnutrition and neurologic disability in Africa.

Malnutrition and neurodisability are both major public health problems in Africa. This review highlights key areas where they interact. This happens throughout life and starts with maternal malnutrition affecting fetal neurodevelopment with both immediate (eg, folate deficiency causing neural tube defects) and lifelong implications (eg, impaired cognitive function). Maternal malnutrition can also increase the risk of perinatal problems, including birth asphyxia, a major cause of neurologic damage and cerebral palsy. Macronutrient malnutrition can both cause and be caused by neurodisability. Mechanisms include decreased food intake, increased nutrient losses, and increased nutrient requirement. Specific micronutrient deficiencies can also lead to neurodisability, for example, blindness (vitamin A), intractable epilepsy (vitamin B6), and cognitive impairment (iodine and iron). Toxin ingestion (eg, from poorly processed cassava) can cause neurodisability including a peripheral polyneuropathy and a spastic paraparesis. We conclude that there is an urgent need for nutrition and disability programs to work more closely together

Using EEG in Resource-Limited Areas: Comparing Qualitative and Quantitative Interpretation Methods in Cerebral Malaria

OBJECTIVE: Our goal was to compare the strength of association and predictive ability of qualitative and quantitative EEG factors with the outcomes of death and neurological disability in pediatric cerebral malaria (CM). METHODS: We enrolled children with a clinical diagnosis of CM admitted to Queen Elizabeth Central Hospital (Blantyre, Malawi) between 2012 and 2017. A routine length EEG was performed within 4 hours of admission. EEG data were independently interpreted using qualitative and quantitative methods by trained pediatric neurophysiologists. EEG interpreters were blinded to patient discharge outcome. RESULTS: EEG tracings from 194 patients were reviewed. Multivariate modeling revealed several qualitative and quantitative EEG variables that were independently associated with outcomes. Quantitative methods modeled on mortality had better goodness of fit than qualitative ones. When modeled on neurologic morbidity in survivors, goodness of fit was better for qualitative methods. When the probabilities of an adverse outcome were calculated using multivariate regression coefficients, only the model of quantitative EEG variables regressed on the neurologic sequelae outcome showed clear separation between outcome groups. CONCLUSIONS: Multiple qualitative and quantitative EEG factors are associated with outcomes in pediatric CM. It may be possible to use quantitative EEG factors to create automated methods of study interpretation that have similar predictive abilities for outcomes as human-based interpreters, a rare resource in many malaria-endemic areas. Our results provide a proof-of-concept starting point for the development of quantitative EEG interpretation and prediction methodologies useful in resource-limited settings

Temporal Trends of Blood Glucose in Children with Cerebral Malaria

Hypoglycemia, defined as a blood glucose \u3c 2.2 mmol/L, is associated with death in pediatric cerebral malaria (CM). The optimal duration of glucose monitoring in CM is unknown. We collected data from 1,674 hospitalized Malawian children with CM to evaluate the association between hypoglycemia and death or neurologic disability in survivors. We assessed the optimal duration of routine periodic measurements of blood glucose. Children with hypoglycemia at admission had a 2.87-fold higher odds (95% CI: 1.35-6.09) of death and, if they survived, a 3.21-fold greater odds (95% CI: 1.51-6.86) of sequelae at hospital discharge. If hypoglycemia was detected at 6 hours but not at admission, there was a 7.27-fold higher odds of death (95% CI: 1.85-8.56). The presence of newly developed hypoglycemia after admission was not independently associated with neurological sequelae in CM survivors. Among all new episodes of blood sugar below a treatment threshold of 3.0 mmol/L, 94.7% occurred within 24 hours of admission. In those with blood sugar below 3.0 mmol/L in the first 24 hours, low blood sugar persisted or recurred for up to 42 hours. Hypoglycemia at admission or 6 hours afterward is strongly associated with mortality in CM. Children with CM should have 24 hours of post-admission blood glucose measurements. If a blood glucose less than the treatment threshold of 3.0 mmol/L is not detected, routine assessments may cease. Children who have blood sugar values below the treatment threshold detected within the first 24 hours should continue to have periodic glucose measurements for 48 hours post-admission