Abstract
HIV infection is widespread throughout the world and is especially prevalent in sub-Saharan Africa and Asia. Similarly, Plasmodium falciparum, the most common cause of severe malaria, affects large areas of sub-Saharan Africa, the Indian subcontinent, and Southeast Asia. Although initial studies suggested that HIV and malaria had independent impact upon patient outcomes, recent studies have indicated a more significant interaction. Clinical studies have shown that people infected with HIV have more frequent and severe episodes of malaria, and parameters of HIV disease progression worsen in individuals during acute malaria episodes. However, the effect of HIV on development of cerebral malaria, a manifestation of P. falciparum infection that is frequently fatal, has not been characterized. We review clinical and basic science studies pertaining to HIV and malaria coinfection and cerebral malaria in particular in order to highlight the likely role HIV plays in exacerbating cerebral malaria pathogenesis.
Highlights
Plasmodium falciparum is the most virulent of the malaria species that infect humans, and it is responsible for the majority of morbidity and mortality due to malaria infection
The majority of these deaths are due to severe malarial anemia and cerebral malaria (CM) and occur in young children in sub-Saharan Africa, where one in every five childhood deaths is due to malaria [196]. 85% of the world’s malaria deaths occur in sub-Saharan Africa
While there have not been extensive clinical studies documenting the effects of HIV coinfection on severe malaria—including cerebral malaria—outcomes, there is growing experimental evidence indicating significant potential for exacerbation of immunologic and physiologic effects of both HIV and malaria
Summary
Plasmodium falciparum is the most virulent of the malaria species that infect humans, and it is responsible for the majority of morbidity and mortality due to malaria infection. 1.2 billion people are at risk for malaria infection, resulting in 225 million infections and 781,000 deaths in 2010 [198] The majority of these deaths are due to severe malarial anemia and cerebral malaria (CM) and occur in young children in sub-Saharan Africa, where one in every five childhood deaths is due to malaria [196]. HIV infects and depletes CD4+ T lymphocytes and monocytes/macrophages, putting patients at risk for opportunistic infection and malignancy, the major causes of death due to HIV and AIDS It has effects on the systemic inflammatory response, causing activation and/or apoptosis in a variety of immune cells as well as elevated levels of proinflammatory cytokines and chemokines in lymph nodes and in the circulation. This inflammatory dysregulation may have important implications for malaria/HIV coinfection, as several pro-inflammatory cytokines have been implicated in the pathogenesis of cerebral malaria, one of the most severe forms of malaria infection
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