Background: Plasmodium falciparum can cause a diffuse encephalopathy known as cerebral malaria (CM), a major contributor to malaria associated mortality. Despite treatment, mortality due to CM can be as high as 30% while 10% of survivors of the disease may experience short-and long-term neurological complications. The pathogenesis of CM and other forms of severe malaria is multi-factorial and appear to involve cytokine and chemokine homeostasis, inflammation and vascular injury/repair. Identification of prognostic markers that can predict CM severity will enable development of better intervention.

Abstract. Pregnancy in sickle cell disease (SCD) patients is associated with increased risk of maternal and fetal mortality. This study determines pregnancy outcomes among women with SCD delivering at Korle-Bu Teaching Hospital, Accra, Ghana. Nine hundred sixty (960) medical records of pregnant women (131 HbSS, 112 HbSC, and 717 comparison group) from 2007 to 2008 were reviewed. The HbSS women were at increased risk of eclampsia (adjusted odds ratio [AOR] = 10.56, 95% confidence interval [CI] = 3.60-30.96, P 0.001), intrauterine growth restriction (AOR = 4.00, 95% CI = 1.38-11.64, P = 0.011), and placenta previa (AOR = 22.03, 95% CI = 9.87-49.14, P 0.001) compared with the comparison group. The HbSC women had increased risk for intrauterine fetal death (AOR = 3.38, 95% CI = 1.15-9.96, P = 0.027) and decreased risk of delivering low birth weight babies (AOR = 0.21, 95% CI = 0.06-0.73, P = 0.014). Women with SCD in Ghana are at a greater risk of morbidity and mortality in pregnancy compared with women without hemoglobinopathies. Improved maternal and fetal outcomes in Ghanaian women with SCD can be achieved through effective intervention by health care providers with thorough knowledge about predisposing factors toward adverse outcomes.

There was no suggestion that exposure to PM directly increased incidence of malaria among infants of multigravidae. In our study area, absence of placental malaria in primigravidae is a marker of low exposure, and this probably explains the lower incidence of malaria-related outcomes among infants of PM-negative primigravidae.

Although the roles played by systemic tumour necrosis factor (TNF) and interleukin 1beta (IL-1beta), and their upregulation of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin, in the pathogenesis of human cerebral malaria (CM) are well established, the role of local cytokine release, in the brain, remains unclear. Immunohistochemistry was therefore used to compare the expression of ICAM-1, VCAM-1, E-selectin, IL-1beta, TNF and transforming growth factor beta (TGF-beta) at light-microscope level, in cryostat sections of cerebral, cerebellar and brainstem tissues collected, post-mortem, from Ghanaian children. Among the 21 children investigated were 10 cases of CM, five of severe malarial anemia (SMA), one of purulent bacterial meningitis (PBM), two of non-central-nervous-system infection (NCNSI) and three children who had no infection (NI) when they died. Parasitised erythrocytes were detected in all of the sections from the cases of fatal malaria (CM and SMA), and sequestered leucocytes were present in most of the sections from the CM cases (but none of the sections from the SMA cases). Significantly elevated vascular expression of all three adhesion molecules investigated was detected in the brains of the 15 cases of fatal malaria and one of the cases of NCNSI (a child with Salmonella septicaemia), and in the malaria cases this showed highly significant co-localization with the areas of erythrocyte sequestration. In terms of the levels of expression of ICAM-1, VCAM-1 and E-selectin, there were, however, negligible differences between the CM and SMA cases. Although TGF-beta showed intravascular and perivascular distribution in all the subjects, its expression was most intense in the PBM case and the CM group. Only in the sections from the PBM and CM cases did TNF and IL-1beta show prominent brain parenchymal staining, in addition to the intravascular and perivascular staining seen in all subjects. The highest observed expression of each of the six antigens studied was in the cerebellar sections of the malaria cases. Endothelial activation in the brain therefore appears to be a feature of fatal malaria and Salmonella sepsis, and in cases of fatal malaria is closely associated with leucocyte sequestration. In the present study, IL-1beta and TNF were only up-regulated in the brains of children with neurodegenerative lesions, whereas TGF-beta was present in all cases.