Samuel D. Kampondeni

Brain Swelling and Death in Children with Cerebral Malaria

BACKGROUNDnCase fatality rates among African children with cerebral malaria remain in the range of 15 to 25%. The key pathogenetic processes and causes of death are unknown, but a combination of clinical observations and pathological findings suggests that increased brain volume leading to raised intracranial pressure may play a role. Magnetic resonance imaging (MRI) became available in Malawi in 2009, and we used it to investigate the role of brain swelling in the pathogenesis of fatal cerebral malaria in African children.nnnMETHODSnWe enrolled children who met a stringent definition of cerebral malaria (one that included the presence of retinopathy), characterized them in detail clinically, and obtained MRI scans on admission and daily thereafter while coma persisted.nnnRESULTSnOf 348 children admitted with cerebral malaria (as defined by the World Health Organization), 168 met the inclusion criteria, underwent all investigations, and were included in the analysis. A total of 25 children (15%) died, 21 of whom (84%) had evidence of severe brain swelling on MRI at admission. In contrast, evidence of severe brain swelling was seen on MRI in 39 of 143 survivors (27%). Serial MRI scans showed evidence of decreasing brain volume in the survivors who had had brain swelling initially.nnnCONCLUSIONSnIncreased brain volume was seen in children who died from cerebral malaria but was uncommon in those who did not die from the disease, a finding that suggests that raised intracranial pressure may contribute to a fatal outcome. The natural history indicates that increased intracranial pressure is transient in survivors. (Funded by the National Institutes of Health and Wellcome Trust U.K.).

Pneumococcal disease in HIV-infected Malawian adults: acute mortality and long-term survival.

ObjectiveHIV-infected patients in Africa are vulnerable to severe recurrent infection with Streptococcus pneumoniae, but no effective preventive strategy has been developed. We set out to determine which factors influence in-hospital mortality and long-term survival of Malawians with invasive pneumococcal disease. Design, setting and patientsAcute clinical features, inpatient mortality and long-term survival were described among consecutively admitted hospital patients with S. pneumoniae in the blood or cerebrospinal fluid. Factors associated with inpatient mortality were determined, and patients surviving to discharge were followed to determine their long-term outcome. ResultsA total of 217 patients with pneumococcal disease were studied over an 18-month period. Among these, 158 out of 167 consenting to testing (95%) were HIV positive. Inpatient mortality was 65% for pneumococcal meningitis (n = 64), 20% for pneumococcaemic pneumonia (n = 92), 26% for patients with pneumococcaemia without localizing signs (n = 43), and 76% in patients with probable meningitis (n = 17). Lowered consciousness level, hypotension, and age exceeding 55 years at presentation were associated with inpatient death, but not long-term outcome in survivors. Hospital survivors were followed for a median of 414 days; 39% died in the community during the study period. Outpatient death was associated with multilobar chest signs, oral candidiasis, and severe anaemia as an inpatient. ConclusionMost patients with pneumococcal disease in Malawi have HIV co-infection. They have severe disease with a high mortality rate. At discharge, all HIV-infected adults have a poor prognosis but patients with multilobar chest signs or anaemia are at particular risk.

Brain imaging in normal kids: a community-based MRI study in Malawian children

To collect normative MRI data for effective clinical and research applications. Such data may also offer insights into common neurological insults.

Magnetic Resonance Imaging Research in Sub-Saharan Africa: Challenges and Satellite-Based Networking Implementation

As part of an NIH-funded study of malaria pathogenesis, a magnetic resonance (MR) imaging research facility was established in Blantyre, Malaŵi to enhance the clinical characterization of pediatric patients with cerebral malaria through application of neurological MR methods. The research program requires daily transmission of MR studies to Michigan State University (MSU) for clinical research interpretation and quantitative post-processing. An intercontinental satellite-based network was implemented for transmission of MR image data in Digital Imaging and Communications in Medicine (DICOM) format, research data collection, project communications, and remote systems administration. Satellite Internet service costs limited the bandwidth to symmetrical 384 kbit/s. DICOM routers deployed at both the Malaŵi MRI facility and MSU manage the end-to-end encrypted compressed data transmission. Network performance between DICOM routers was measured while transmitting both mixed clinical MR studies and synthetic studies. Effective network latency averaged 715 ms. Within a mix of clinical MR studies, the average transmission time for a 256 × 256 image was ~2.25 and ~6.25 s for a 512 × 512 image. Using synthetic studies of 1,000 duplicate images, the interquartile range for 256 × 256 images was [2.30, 2.36] s and [5.94, 6.05] s for 512 × 512 images. Transmission of clinical MRI studies between the DICOM routers averaged 9.35 images per minute, representing an effective channel utilization of ~137% of the 384-kbit/s satellite service as computed using uncompressed image file sizes (including the effects of image compression, protocol overhead, channel latency, etc.). Power unreliability was the primary cause of interrupted operations in the first year, including an outage exceeding 10 days.

The effect of a tuberculosis chest X-ray image reference set on non-expert reader performance

AbstractObjectivesIn low-resource settings, limitations in diagnostic accuracy of chest X-rays (CXR) for pulmonary tuberculosis (PTB) relate partly to non-expert interpretation. We piloted a TB CXR Image Reference Set (TIRS) to improve non-expert performance in an operational setting in Malawi.MethodsNineteen doctors and clinical officers read 60 CXR of patients with suspected PTB, at baseline and using TIRS. Two officers also used the CXR Reading and Recording System (CRRS). Correct treatment decisions were assessed against a “gold standard” of mycobacterial culture and expert performance.ResultsTIRS significantly increased overall non-expert sensitivity from 67.6 (SD 14.9) to 75.5 (SD 11.1, Pu2009=u20090.013), approaching expert values of 84.2 (SD 5.2). Among doctors, correct decisions increased from 60.7xa0% (SD 7.9) to 67.1xa0% (SD 8.0, Pu2009=u20090.054). Clinical officers increased in sensitivity from 68.0xa0% (SD 15) to 77.4xa0% (SD 10.7, Pu2009=u20090.056), but decreased in specificity from 55.0xa0% (SD 23.9) to 40.8xa0% (SD 10.4, Pu2009=u20090.049). Two officers made correct treatment decisions with TIRS in 62.7xa0%. CRRS training increased this to 67.8xa0%.ConclusionUse of a CXR image reference set increased correct decisions by doctors to treat PTB. This tool may provide a low-cost intervention improving non-expert performance, translating into improved clinical care. Further evaluation is warranted.Key Points• Tuberculosis treatment decisions are influenced by CXR findings, despite improved laboratory diagnostics.n • In low-resource settings, CXR interpretation is performed largely by non-experts.n • We piloted the effect of a simple reference training set of CXRs.n • Use of the reference set increased the number of correct treatment decisions. This effect was more marked for doctors than clinical officers.n • Further evaluation of this simple training tool is warranted.

Cerebrospinal fluid Plasmodium falciparum histidine-rich protein-2 in pediatric cerebral malaria

BackgroundCerebral malaria (CM) causes a rapidly developing coma, and remains a major contributor to morbidity and mortality in malaria-endemic regions. This study sought to determine the relationship between cerebrospinal fluid (CSF) Plasmodium falciparum histidine rich protein-2 (PfHRP-2) and clinical, laboratory and radiographic features in a cohort of children with retinopathy-positive CM.MethodsPatients included in the study were admitted (2009–2013) to the Pediatric Research Ward (Queen Elizabeth Central Hospital, Blantyre, Malawi) meeting World Health Organization criteria for CM with findings of malarial retinopathy. Enzyme-linked immunosorbent assay was used to determine plasma and CSF PfHRP-2 levels. Wilcoxon rank-sum tests and multivariable logistic regression analysis assessed the association of clinical and radiographic characteristics with the primary outcome of death during hospitalization.ResultsIn this cohort of 94 patients, median age was 44 (interquartile range 29–62) months, 53 (56.4%) patients were male, 6 (7%) were HIV-infected, and 10 (11%) died during hospitalization. Elevated concentrations of plasma lactate (pu2009=u20090.005) and CSF PfHRP-2 (pu2009=u20090.04) were significantly associated with death. On multivariable analysis, higher PfHRP-2 in the CSF was associated with death (odds ratio 9.00, 95% confidence interval 1.44–56.42) while plasma PfHRP-2 was not (odds ratio 2.05, 95% confidence interval 0.45–9.35).ConclusionsElevation of CSF, but not plasma PfHRP-2, is associated with death in this paediatric CM cohort. PfHRP-2 egress into the CSF may represent alteration of blood brain barrier permeability related to the sequestration of parasitized erythrocytes in the cerebral microvasculature.

Validation of diffusion measurements obtained on a 0.35 T MR in Malawi: Important insights for radiologists in low income settings with low field MRI

PURPOSEnTo investigate the reliability of diffusion weighted image (DWI) measurements obtained on a 0.35T MR scanner in Malawi for malaria research.nnnMATERIALS AND METHODSnThe same healthy volunteers (n=6) were scanned on a 0.35T MR scanner in Malawi and a 3T scanner in the US. Three subjects had two repeated DWI scans at 0.35T. Due to scanner constraints, only three diffusion gradient directions for DWI on 0.35T could be obtained. An apparent diffusion coefficient (ADC) map was reconstructed from the 0.35T and the result was compared to standard DWI acquisition on the 3T scanner. The mean ADC from 15 different regions and the voxel-wise coefficient of variation (CV) were calculated to investigate the intra-scanner and inter-scanner variability. Reproducibility was calculated using intra-class correlation coefficient (ICC).nnnRESULTSnThe 0.35T intra-scanner ADC repeatability was high for all three subjects with repeated scans (ICC>0.7). The intra-scanner correlation between repeated scans was also high (r>0.67, p< 0.01). Comparing the ADC findings from the 0.35T and 3T MRs, the high inter-scanner correlation suggested that the 0.35T ADC results were valid (ICC>0.7, r>0.5, p<0.01). Voxel-wise CV revealed a few regions with larger variation (CV>20%), which were primarily located in peripheral regions and the boundary of lateral ventricles, and likely due to partial volume effects in low field scans.nnnCONCLUSIONnThese findings support the validity of DWI obtained from low field MR scanners used in many low income countries.