Plasmodium berghei ANKA infection induces thymocyte apoptosis and thymocyte depletion in CBA mice

Immune responses to malaria infections are characterized by strong T and B cell activation, which, in addition of potentially causing immunopathology, are of poor efficacy against the infection. It is possible that the thymus is involved in the origin of immunopathological reactions and a target during malaria infections. This work was developed in an attempt to further clarify these points. We studied the sequential changes in the thymus of CBA mice infected with Plasmodium berghei ANKA, a model in which 60-90 percent of the infected animals develop cerebral malaria. During the acute phase of infection, different degrees of thymocyte apoptosis were recorded: (1) starry-sky pattern of diffuse apoptosis with maintenance of cortical-medullary structure; (2) intense apoptosis with cortical atrophy, with absence of large cells; (3) severe cortical thymocyte depletion, resulting in cortical-medullary inversion. In the latter, only residual clusters of small thymocytes were observed within the framework of epithelial cells. The intensity of thymus alterations could not be associated with the degree of parasitemia, the expression of clinical signs of cerebral malaria or intensity of brain lesions. The implications of these events for malaria immunity and pathology are discussed.

Severe anemia affects both splenectomized and non-splenectomized Plasmodium falciparum-infected Aotus infulatus monkeys

Severe anemia is the earliest and a frequently fatal complication of Plasmodium falciparum infection. Here we describe Aotus infulatus as a primate model suitable to study this malaria complication. Both non-splenectomized and splenectomized monkeys receiving different inocula of P. falciparum FVO strain presented large (> 50 percent) decreases in hematocrit values during infection. Non-splenectomized animals were able to control parasite growth (parasitemia did not exceed 4 percent), but they had to be treated because of severe anemia. Three of 4 splenectomized monkeys did not control parasitemia and were treated, but developed severe anemia after treatment when presenting a negative blood film. Destruction of parasitized red blood cells alone cannot account for the degree of anemia. Non-splenectomized monkeys repeatedly infected with homologous parasites became rapidly and progressively resistant to reinfection and to the development of severe anemia. The data presented here point to A. infulatus as a suitable model for studying the pathogenesis of severe malarial infection

The new and the old in malaria immunopathology

O termo "imunopatologia" pode ser considerado tanto como "uma patologia do sistema imune" quanto como "uma patologia provocada pelo sistema imune". Isso se aplica também no caso de infecções parasitárias como a malária na qual ambos os tipos de fenômeno säo comumente observados. Por quase meio século após a descoberta do Plasmodium, clínicos e patologistas deixaram-se seduzir pela fácil tentaçäo de explicar fenômenos como a anemia e a malária cerebral como complicações mecânicas da doença, resultantes da açäo direta de formas maduras do parasita, destruindo hemácias ou obliterando vasos capilares profundos. Nas últimas décas, entretanto, progressos substanciais no conhecimento da estrutura e funções das citocinas levaram a uma profunda revoluçäo na maneira de se ver a patologia da malária. Os conceiros atuais tendem a considerar que a maior parte da patogenia da malária resulta da interaçäo de distintos processos, e a dar mais ênfase ao efeito modulador de toxinas parasitárias na cascata de ativaçäo de citocinas do que aos óbvios componentes mecânicos da infecçäo parasitária. Neste artigo, revisamos criticamente alguns aspectos da patologia da malária que poderiam resultar de um sistema imune alterado. A anemia e a forma cerebral da malária Plasmodium falciparum assim como o envolvimento renal que acompanha a infecção por P. malariae. Também discutimos os mecanismos envolvidos nas perturbações do sistema imune. Ativação policlonal linfocitária, autoimunidade e imunodepressão.

Aotus infulatus monkey is susceptible to Plasmodium falciparum infection and may constitute an alternative experimental model for malaria

Aotus is one of the WHO-recommended primate models for studies in malaria, and several species can be infected with Plasmodium falciparum or P. vivax. Here we describe the successful infection of the species A. infulatus from eastern Amazon with blood stages of P. falciparum. Both intact and splenectomized animals were susceptible to infection; the intact ones were able to keep parasitemias at lower levels for several days, but developed complications such as severe anemia; splenectomized monkeys developed higher parasitemias but no major complications. We conclude that A. infulatus is susceptible to P. falciparum infection and may represent an alternative model for studies in malaria.

Clinical and laboratory findings of disseminated Mycobacterium avium complex infection (DMAC) in a pair matched case-control study

A pair matched case/control study was conducted from January 1991 to 30 June 1992 in order to define clinical and laboratory findings associated with DMAC infection in AIDS patients. Since DMAC infection is usually associated with advanced immunodeficiency, and therefore also with other opportunistic illnesses, in addition to the number of CD4+ lymphocytes, cases and controls were matched using the following criteria: date of AIDS diagnosis and antiretroviral therapy, number and severity of associated opportunistic infections and, whenever possible, type of Pneumocystis carinii prophylaxis, age and gender, in this order of relevance. Cases (defined as patients presenting at least one positive culture for MAC at a normally sterile site) and controls presented CD4+ lymphocyte counts below 50 cel/mm3. A significantly higher prevalence of general, digestive and respiratory signs, increased LDH levels, low hemoglobin levels and CD4+ cell counts were recorded for cases when compared to controls. Increases in gammaGT and alkaline phosphatase levels seen in cases were also recorded for controls. In conclusion, the strategy we used for selecting controls allowed us to detect laboratory findings associated to DMAC infection not found in other advanced immunossupressed AIDS patients without DMAC