Inflammation and Elevated Osteopontin in Plasma and CSF in Cerebral Malaria Compared to Plasmodium-Negative Neurological Infections.

Cerebral malaria in young African children is associated with high mortality, and persisting neurological deficits often remain in survivors. Sequestered Plasmodium-infected red blood cells lead to cerebrovascular inflammation and subsequent neuroinflammation. Brain inflammation can play a role in the pathogenesis of neurologic sequelae. Therefore, we assessed a select set of proinflammatory analytes (IP10, IL23, MIP3α, GRO, MCP-1, and osteopontin in both the plasma and cerebrospinal fluid(CSF) of Zambian children with cerebral malaria and compared this with children with neurological symptoms that were negative for Plasmodium falciparum (non-cerebral malaria). Several similarities in plasma and CSF levels were found, as were some striking differences. We confirmed that IP10 levels were higher in the plasma of cerebral malaria patients, but this was not found in CSF. Levels of osteopontin were elevated in both the plasma and CSF of CM patients compared to the non-CM patients. These results show again a highly inflammatory environment in both groups but a different profile for CM when compared to non-cerebral malaria. Osteopontin may play an important role in neurological inflammation in CM and the resulting sequelae. Therefore, osteopontin could be a valid target for further biomarker research and potentially for therapeutic interventions in neuroinflammatory infections.

Evaluation of the SD bioline cholera rapid diagnostic test during the 2016 cholera outbreak in Lusaka, Zambia.

OBJECTIVE: To assess the performance of the SD Bioline Cholera Ag O1/O139 rapid diagnostic test (RDT) compared to a reference standard combining culture and PCR for the diagnosis of cholera cases during an outbreak. METHODS: RDT and bacterial culture were performed on site using fresh stools collected from cholera suspected cases, and from stools enriched in alkaline peptone water. Dried stool samples on filter paper were tested for V. cholerae by PCR in Lusaka (as part of a laboratory technology transfer project) and at a reference laboratory in Paris, France. A sample was considered positive for cholera by the reference standard if any of the culture or PCR tests was positive for V. cholerae O1 or O139. RESULTS: Among the 170 samples tested with SD Bioline and compared to the reference standard, the RDT showed a sensitivity of 90.9% (95% CI: 81.3-96.6) and specificity of 95.2% (95% CI: 89.1-98.4). After enrichment, the sensitivity was 95.5% (95% CI: 87.3-99.1) and specificity 100% (95% CI: 96.5-100). CONCLUSION: The observed sensitivity and specificity were within recommendations set by the Global Task Force for Cholera Control on the use of cholera RDT (sensitivity = 90%; specificity = 85%). Although the sample size was small, our findings suggest that the SD Bioline RDT could be used in the field to rapidly alert public health officials to the likely presence of cholera cases when an outbreak is suspected.

Elevated brain derived neurotrophic factor in plasma and interleukin-6 levels in cerebrospinal fluid in meningitis compared to cerebral malaria.

Neurological infections, such as Cerebral malaria (CM) and meningitis are associated with high mortality and in survivors, particularly young children, persistent neurologic deficits often remain. As brain inflammation plays a role in the development of these neurological sequelae, multiplex assays were used to assess a select set of immune mediators in both plasma and cerebrospinal fluid (CSF) from Zambian children with neurological infections. Both CM and meningitis patients showed high levels of markers for vascular inflammation, such as soluble ICAM-1 and angiopoietins. Although high levels of angiopoietin 1 and angiopoietin 2 were found in the meningitis group, their levels in the CSF were low and did not differ. As expected, there were high levels of cytokines and notably a significantly elevated IL-6 level in the CSF of the meningitis group. Interestingly, although elevated levels BDNF were found, BDNF levels were significantly higher in plasma of the meningitis group but similar in the CSF. The striking differences in plasma BDNF and IL-6 levels in the CSF point to markedly different neuro-pathological processes. Therefore, further investigations in the role of both IL-6 and BDNF in the neurological outcomes are needed.