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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seventy five patients with large spleens were investigated in order to establish the causes of splenomegaly in Northern Nigeria, to define further the diagnostic criteria of tropical splenomegaly syndrome (TSS), and to study its pathogenesis. Investigations included examination of liver biopsy, bone marrow cytology, lymphocyte response to phytohaemagglutinin (PHA), serum immunoglobulins and complement, and the presence of immunoglobulin and complement fixed in Kupffer cells. Thirty patients had TSS, five chronic lymphatic leukaemia (CLL), four a syndrome of gross lymphoid hyperplasia (GLH) distinct from TSS, CLL and the lymphomas, and twenty three miscellaneous conventional diseases. In thirteen cases no definite diagnosis could be established. TSS was found to be predominantly a disease of female Fulani cattle herders. Its essential characteristics were splenomegaly in the presence of acquired immunity to malaria, a grossly raised serum IgM, a lowered serum complement, and the presence of IgM fixed in Kupffer cells. There was lymphoid hyperplasia in bone marrow, hepatic sinusoids and often blood which may be indistinguishable from that in CLL. Lymphocytes undergo normal blastogenesis to PHA. There was clinical and haematological response to proguanil therapy. Reticuloendothelial phagocytosis of IgM, probably as a complex, seems to be the essential feature of the condition. As it was impossible to identify early cases of TSS it is unclear whether IgM overproduction or phagocytosis of IgM complexes is the first stage of the disease. The precise nature of the association with malaria remains obscure. The diagnosis of CLL demanded the demonstration of an abnormally low immunoglobulin level and impaired lymphocyte responsiveness to PHA by blast transformation or 3H-thymidine incorporation, in addition to the usual haematological findings. The syndrome GLH occurred in multiparous Hausa women. It was characterised by intense lymphocytosis with active, PHA-responsive cells, and normal immunoglobulin levels. Patients responded to proguanil therapy. It is suggested that these patients have a depressed immune response to malaria, perhaps through repeated pregnancies, and to a leukaemogenic agent, both of which stimulate lymphocytosis. Antimalarial treatment at this stage may prevent the development of frank leukaemia or lymphoma. The usefulness of the various investigative procedures and the problem of managing the large number of undiagnosed cases are discussed.
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PMID:Splenomegaly in Northern Nigeria. 1 54

Malaria remains prevalent throughout tropical and subtropical regions and almost a third of the World's population is exposed to the risk of infection. There is currently a serious resurgence of the disease in Asia and Central America. The failure of global eradication measures based upon the use of insecticides and chemotherapy has resulted from difficulties of practical implementation compounded by the spread of insecticide and drug resistance. Repeated natural infection does not produce detectable resistance to the exo-erythrocytic cycle of malaria in man. Irradiated sporzoite vaccines do, however, induce stage specific immunity in murine malaria and in a proportion of human subjects. Vaccinated individuals remain susceptible to blood stage infection which causes clinical malaria. In addition the vaccine is unstable and must be administered by intravenous inoculation. Since neither sporogonic nor exo-erythrocytic parasite development is cyclical in human malarias, there is little prospect for vaccine production through cultivation of these stages. The inhabitants of hyperendaemic areas become increasingly resistant to malaria during childhood and adolescence, through the slow development of specific, acquired immunity to asexual blood stage parasites. Immunity is mediated by antibody, which blocks merozoite invasion of red cells, as well as by cell mediated mechanisms and non-specific cytotoxic agents. Vaccination with merozoites induces long lasting immunity of broad serological specificity active against the blood-stage of the parasite. Merozoite vaccines can be preserved by freeze drying and harvested from continuous cultures of blood stage parasites. The major problem in development of a human merozoite vaccine concerns the requirement for Freund's complete adjuvant which is not acceptable for man. The effective immunity induced by vaccination contrasts with the slow development of incomplete resistance which follows repeated natural infection. The latter is associated with the generation of immune suppressor cells, lymphoid cell mitogens and soluble antigens, and in some species by the occurrence of antigenic variation--all of which may favour parasite survival. It is probable that vaccination with non-viable antigen of appropriate composition, induces immune effector processes without activating mechanisms which allow parasites to escape the consequences of immunity. Many effective vaccines such as those against measles, poliomyelitis, tetanus and rabies are commercially available but barely used in the developing world. The affected nations cannot afford their purchase, nor do the means exist for their distribution. It follows that if a safe and effective malaria vaccine were to be developed, its bulk manufacture and administration would require massive international support and cooperation.
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PMID:Immunity to malaria. 3 57

Malaria-induced immunosuppression has been demonstrated in humans and experimental animals. The suppressed immune response has been suggested to be primarily humoral and not cellular in nature, since classical lymphocytic cell-mediated responses have been reported to be normal. Since previous results have demonstrated that an impairment in macrophage antigen processing may be a contributing factor in malaria-induced immunosuppression, the present studies were conducted to determine if the macrophage/reticuloendothelial system (RES) alteration occurs parallel to the course of the malarial infection and if the impairment in antibody formation is temporally related to the RES alteration. The present study has demonstrated that a profound impairment in splenic direct plaque forming cell (PFC) formation occurs in malaria-infected Balb/c mice which had been immunized with sheep erythrocytes (SRBC) either 2 or 4 days after inoculation with Plasmodium berghei, NYU-2 strain. Serum hemagglutinin titers were significantly depressed in mice which received the SRBC 4 days post-inoculation; however, no alterations in antibody titers were observed in mice immunized with SRBC 2 days post-inoculation. Coincident with the depression of serum antibody titers at the day 4 immunization period was a profound increase in the vascular clearance of 51Cr-SRBC with an enhanced hepatic uptake of the 51Cr-SRBC and a decreased splenic localization of the labelled erythrocytes. It is suggested that a direct vascular exposure of the splenic lymphoid-macrophage elements to the parasite may be responsible for the initial early alterations in the PFC response while the impairment in serum antibody titers and splenic phagocytic activity may be a result of the pathological alterations occurring later in the infection, e.g., tissue anoxia, anemia, and hemolysis.
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PMID:A temporal relationship between reticuloendothelial system phagocytic alterations and antibody responses in mice infected with Plasmodium berghei (NYU-2 strain). 76 77

A natural body protein is probably a major cause of the deadliest complication of malaria, a finding that could point toward new methods of treatment. Studies in an experimental model indicate that tumor necrosis factor (TNF), a protein also known as cachectin, is an essential element in highly fatal cerebral malaria. This contention is supported by the following observations. First, during the course of an infection by P. berghei ANKA strain, mice of a CM-susceptible strain express markedly elevated levels of TNF in their serum at the time that neurological signs are evident. Second, in contrast, either mice from nonsusceptible strains, susceptible strains depleted of CD4+ T lymphocytes, or susceptible mice inoculated with malaria organisms incapable of producing CM all fail to express high serum TNF activity. Third, passive immunization against mouse TNF significantly prolong the survival of P. berghei-infected CBA/Ca mice, and prevented the development of neurologic signs to an extent that was highly significant. Treatment with the anti-TNF antibody also prevents the histopathological lesions that are characteristic of CM, i.e. plugging of cerebral vessels by macrophages, lymphoid and parasitized erythrocytes. We have recently shown that this increased TNF release and macrophage accumulation are schematically made of two components, each mediated by different cytokines presumably released by stimulated CD4+ T lymphocytes: (a) a quantitative component: increased accumulation of macrophages results from the concomitant release of IL-3 and GM-CSF, and (b) a qualitative component: macrophage number has not only to be raised, but macrophages need to be activated by IFN-gamma. Thus, CM appears to be the result of a cytokine cascade mediated by the immune response. TNF might also be involved in the pathogenesis of human cerebral malaria. Indeed, we have recently shown that in african children with falciparum malaria, elevated serum concentrations of this molecule are associated with severe neurological involvement and fatal outcome. Clinical trials of treatment with monoclonal anti-TNF antibodies are presently underway in an attempt to reduce mortality and morbidity in african children with cerebral malaria.
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PMID:Essential role of tumor necrosis factor and other cytokines in the pathogenesis of cerebral malaria: experimental and clinical studies. 135 36

The function of c-myc in physiology is only partially known. Its product has DNA binding properties and plays a role in the control of proliferation and differentiation. In general, increased c-myc expression leads to proliferation and abolishment of differentiation. The involvement of c-myc in mouse plasmacytomas and human Burkitt's lymphoma is well known: due to chromosomal translocation c-myc comes under the influence of regulatory elements of immunoglobulin genes, leading to increased expression of the gene and proliferation of the cells. In man, the chromosomal translocations may occur within the increased pool of (pre) B-cells due to Epstein Barr virus (EBV) and malaria infection with subsequent immunosuppression. Apart from these early (primary?) events in lymphomagenesis, c-myc is also often involved in tumour progression, probably by a similar mechanism. Different types of c-myc involvement are associated with specific types of lymphoma: there are differences between endemic, sporadic and ileocecal Burkitt's lymphoma as well as between those and primary extranodal large cell lymphoma and large cell lymphoma which has progressed. These differences are associated with the differentiation of the involved lymphoid cells and may point to the stage of differentiation in which the oncogenic event occurred.
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PMID:The association of c-myc rearrangements with specific types of human non-Hodgkin's lymphomas. 149 39

1. Rodent experimental models have been useful to study severe malaria but few serial and controlled studies have been conducted. In the present investigation, we describe the histopathology of lethal and non-lethal rodent malaria induced by Plasmodium berghei and P. chabaudi. P. berghei malaria shows a uniformly lethal course, while P. chabaudi malaria produces a non-lethal acute infection with recovery and periodical recrudescences. Sequential histopathological changes were also characterized in P. chabaudi malaria to determine the evolution of the lesions. 2. P. berghei-infected mice have a more severe organ involvement and lower blood regenerative changes than P. chabaudi-infected mice. Two patterns of organ involvement were observed by comparing the two infections. The first is related to nonspecific parasitized red blood cell clearance by liver and spleen. The second is related to specific changes due to a specific parasite strain interaction with the host, such as those found in the lungs. 3. Sequential changes in P. chabaudi-infected mice were characterized by perihepatocytic reticulin fiber deposition during the recovery from infection, which faded in subsequent stages. Other organs had a similar regressive evolution, except splenic lymphoid tissue which underwent histological restoration or even hypertrophy after depletion in the acute stage. No brain or heart lesions were observed in either model during the acute and subsequent stages. 4. P. chabaudi infection, whose histopathology is described here for the first time, should be useful as a non-lethal experimental model to study the evolution of histopathological alterations in malaria.
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PMID:Comparative and sequential histopathology of Plasmodium chabaudi-infected Balb/c mice. 184 71

Sixteen patients suffering from acute Plasmodium falciparum malaria were studied. All were residents of an area of unstable malaria-transmission in Eastern Sudan. Blood-samples were drawn at diagnosis, and 7 and 30 days later. Blood-samples from thirteen donors, drawn outside the malaria transmission season 5 months prior to the attack, were included in the study. Lymphoproliferative responsiveness to purified soluble malarial antigens and to the unrelated antigen PPD was lost during the acute phase of the disease in most donors, but was regained during convalescence, except in four donors recrudescing or reinfected by day 30. In contrast to the suppression of antigenic responses, cellular responses to phytohaemagglutinin (PHA) remained virtually unaffected. All donors showed elevated plasma-levels of soluble IL-2 receptor during the acute phase of the disease which normalized during convalescence. Five donors examined by fluorescence-activated cell sorting (FACS) showed no increase in surface expression of IL-2 receptor on peripheral lymphocytes. The data indicate that acute P. falciparum malaria causes a depletion of antigen-reactive T-cells from the peripheral circulation, probably due to homing of this cell-population to lymphoid tissues. It was also found that acute-phase plasma was suppressive to PPD-induced proliferative responses, indicating an additional suppressive mechanism operating in vivo.
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PMID:Loss of cellular immune reactivity during acute Plasmodium falciparum malaria. 193 Nov 34

Burkitt's lymphoma is the most common childhood cancer in Africa. Most prevalent in areas endemic for malaria, the disease, a malignant growth of lymphoid tissue, usually presents itself as a large tumour of the jaw. When first characterized in the 1950s, the lymphoma was thought to spread by some infectious agent. Subsequent research indicates that the frequent involvement of an infectious agent is but one factor in a more complex aetiology. Today, Burkitt's lymphoma is considered an example of multistep carcinogenesis. Each step in the process results from a different agent. The agent in the first step is the Epstein-Barr virus, which infects B cells of the immune system causing a proliferation of these cells. The second step, malarial infection, furthers the proliferation of B cells providing a large population of cells available for a chromosomal translocation which represents the third step in the formation of the lymphoma. The chromosomal translocation places a cancer causing gene, c-myc, in close proximity to an active antibody-encoding its proliferation resulting in a cell capable of unlimited growth which serves as the nucleus of a B cell lymphoma.
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PMID:Burkitt's lymphoma and the role of Epstein-Barr virus. 216 60

Experimental cerebral malaria (ECM), a lethal hyperacute neurological syndrome associated with high blood levels of tumor necrosis factor, develops in genetically susceptible (CBA/Ca) mice 7 days after infection with Plasmodium berghei ANKA strain. Injections of neutralizing monoclonal antibody against recombinant murine interferon gamma, not later than 4 days after infection, markedly reduced the incidence of ECM and the elevation in serum levels of tumor necrosis factor. This treatment prevented the cerebral lesions (plugging of brain vessels by monocytes, lymphocytes, and parasitized erythrocytes). In contrast, the extent of macrophage infiltration in lymphoid organs (which is a characteristic feature of mice developing ECM), as well as the course of infection, remained unaffected by the antibody treatment. Protected mice died at a later time of severe anemia and overwhelming parasitemia, the usual outcome of P. berghei infection in mice that are not susceptible to ECM. The present data indicate that interferon gamma constitutes an important link in the cytokine network that leads to brain vessel inflammation in experimental malaria. It is proposed that interferon gamma released by activated CD4+ T cells acts by augmenting both production and action of tumor necrosis factor.
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PMID:Monoclonal antibody against interferon gamma can prevent experimental cerebral malaria and its associated overproduction of tumor necrosis factor. 250 93

This work characterizes the erythropoietic interplay of the spleen, blood, and bone marrow in a lethal murine malaria, strain 17XL P. yoelii. This malaria runs a fulminant 7 day course in BALB/c/ByJ mice, marked by high levels of parasitized reticulocytes with death likely due to anemia. We have quantitated the levels of burst forming units-erythroid (BFU-E), the early, niche-seeking, largely erythropoietin-unresponsive erythropoietic precursors, and of colony forming units-erythroid (CFU-E), the more differentiated sessile erythropoietin-responsive precursors, in bone marrow, blood, and spleen, through the course of this malaria. A decline in marrow BFU-E began on day 2, but recovered, relatively, after day 3. Marrow cellularity declined, being but 75% normal on day 6. Spleen weight increased about 5-fold within 6 days with enlargement of erythroid, lymphoid, macrophage, and stromal compartments. Splenic BFU-E increased in the first 24 hr and 5-fold by day 6. Splenic CFU-E increased in the first 24 hr and into day 4. They then declined and showed a secondary, large-scale, sustained rise interrupted by death. Because the spleen was enlarging, a greater than 60-fold increase in the absolute number of splenic CFU-E occurred at the time of death. Marrow CFU-E followed the same pattern as splenic CFU-E, but the terminal increase represented but a 4-fold absolute increase because of declining marrow cellularity. High levels of erythropoietin occurred only late in the course of disease, likely in response to profound anemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of splenic control of murine malaria: tissue culture studies of the erythropoietic interplay of spleen, bone marrow, and blood in lethal (strain 17XL) Plasmodium yoelii malaria in BALB/c mice. 277 62


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