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K Marsh

Publications and source records attributed to K Marsh.

223 records · Page 13Linked to original sources
PubMedDate not supplied

A review of the spectrum of clinical ocular fundus findings in P. falciparum malaria in African children with a proposed classification and grading system.

Ocular fundus pathology in Plasmodium falciparum malaria is common and has prognostic significance. We have made a collaborative effort to document the ocular features in several populations. Based on examination of 735 patients in Malawi, Kenya and The Gambia by direct and indirect ophthalmoscopy with dilated pupils, we have determined that the 5 distinct clinical features (in order of frequency) include retinal whitening, haemorrhages, unique vessel abnormalities, papilloedema, and cotton wool spots. Photographs and descriptions of these are presented, along with a proposed grading scheme.

Child↗
PubMedDate not supplied

Cognitive sequelae of severe malaria with impaired consciousness.

Although cerebral malaria is the most common acute encephalopathy arising in children in Africa little is known of its effect upon the longer-term cognitive development of survivors. In Kenya, we compared the performance of 87 survivors of severe malaria with impaired consciousness to matched community controls on a wide range of tasks, not less than 42 months post illness episode. The presence of cognitive impairment was then related to both the pattern of symptoms at the time of the acute illness and the presence of gross neurological impairment on discharge. Significant group differences were found in areas of cognitive functioning suggestive of widespread impairment in the development of the ability to initiate, plan and carry out tasks (the executive functions). On tasks of more discrete cognitive skills (information processing) there were no significant group differences, although impaired performance was found more frequently in the severe malaria group. The odds ratio associated with the development of cognitive impairment following severe malaria with impaired consciousness was found to be 4.48 (95% CI 1.22, 16.47). A combination of 4 signs (coma, hypoglycaemia, seizures, and absence of hyperpyrexia) proved to have greater accuracy than the presence of gross neurological sequelae in predicting cognitive impairment (95% vs 93% specificity, 67% vs 58% sensitivity).

Child↗
PubMedDate not supplied

T-cell control of Epstein-Barr virus-infected B cells is lost during P. falciparum malaria.

Endemic Burkitt's lymphoma, a tumour of children in which B lymphocytes are infected with Epstein-Barr virus (EBV), is common in areas of Africa where malaria is holoendemic. The tumour is characterized by chromosome translocations; usually the terminal portion of chromosome 8 containing the c-myc gene is translocated to chromosome 14, near the enhancer of the immunoglobulin heavy-chain locus. Less frequent are translocations of chromosome 8 to the kappa light-chain locus of chromosome 2 or to the lambda light-chain locus of chromosome 22. In vitro, EBV induces B cells to proliferate and secrete immunoglobulin and antibody. However, in vivo the infected B lymphocytes are under immunological control, so that abnormal proliferation is found only in immunosuppressed patients. Such patients are subsequently liable to develop lymphomas. Burkitt believed that the tumour he had described resulted from interaction between a virus(es) and a "reticuloendothelial system altered by chronic and heavy infection by malarial or other parasites". We report here that during an attack of Plasmodium falciparum malaria, T-cell subpopulations are radically altered so that, in vitro, B lymphocytes infected with EBV proliferate abnormally to secrete large amounts of immunoglobulin and antibody. This phenomenon offers some explanation for the increased incidence of Burkitt's tumour and the high levels of immunoglobulin found in people living in areas where P. falciparum malaria is common.

Adolescent↗
PubMedDate not supplied

Regulation of immune response by Plasmodium-infected red blood cells.

During the asexual blood stage infection of the human malaria parasite, Plasmodium falciparum, parasite-derived proteins are inserted onto the surface of the host red blood cell membrane. These proteins are highly variable and were originally thought only to mediate antigenic variation, and sequestration of parasites from peripheral circulation, thus enabling immune evasion. Recent studies have revealed that PfEMP-1 and other molecules on the P. falciparum-infected red blood cell (PfRBC) activate and modulate the immune response. In this review, we discuss how PfRBCs interact with antigen-presenting cells (APCs) and other cells of the immune system, and how such interactions could modulate the host response to Plasmodium infections.

Animals↗
PubMedDate not supplied

Immune effector mechanisms in malaria.

That humans in endemic areas become immune to malaria offers encouragement to the idea of developing protective vaccines. However natural immunity is relatively inefficient, being bought at the cost of substantial childhood mortality, and current vaccines are only partially protective. Understanding potential targets and mechanisms of protective immunity is important in the development and evaluation of future vaccines. Some of the problems in identifying such targets and mechanisms in humans naturally exposed to malaria may stem from conceptual and methodological issues related to defining who in a population is susceptible, problems in defining immune responsiveness at single time points and issues related to antigenic polymorphism, as well as the failure of many current approaches to examine functional aspects of the immune response. Protective immune responses may be directed to the pre erythrocytic parasite, to the free merozoite of the blood stage parasite or to new antigens induced on the infected red cell surface. Tackling the methodological issues of defining protection and immune response, together with studies that combine functional assays with new approaches such as allelic exchange and gene knock out offer opportunities for better defining key targets and mechanisms.

Adolescent↗
PubMedDate not supplied

Identification of frequently recognized dimorphic T-cell epitopes in plasmodium falciparum merozoite surface protein-1 in West and East Africans: lack of correlation of immune recognition and allelic prevalence.

The merozoite surface protein-1 (MSP1) is the most studied malaria blood-stage vaccine candidate. Lymphokines such as interferon gamma (IFN-gamma) and interleukin 4 (IL-4) may mediate blood-stage specific protection. Here we identify Plasmodiumfalciparum MSP1 T-cell epitopes capable of rapid induction of IFN-gamma and/or IL-4 from peripheral blood mononuclear cells of East and West African donors. Both allelic forms of these novel MSP1 T-cell epitopes were stimulatory. An unusually high numbers of Gambian responders (> 80%) to these epitopes were observed, suggesting that MSPI reactivity may have been underestimated previously in this population. Surprisingly, IFN-gamma responses to allelic T-cell epitopes failed to correlate with differential antigenic exposure in The Gambia compared to Kenya. These results suggest an unexpected level of immunoregulation of IFN-gamma response with variable allelic T-cell reactivity independent of the level of antigenic exposure. Further analysis of the mechanisms determining this response pattern may be required if vaccines are to overcome this allelic reactivity bias in malaria-exposed populations.

Adolescent↗