Genetic Control of Host Resistance to Malaria
Mary M. Stevenson in Malaria: Host Responses to Infection, 2017
Variation in the level of resistance to infection with another strain of P. berghei, P. berghei ANKA, has also been demonstrated.52,53 Analysis of the level of resistance in four inbred strains and one outbred strain showed that the level of parasitemia, the degree of anemia, and the level of specific antibody, although characteristic for each strain, did not correlate with susceptibility. Although immune complexes containing either IgM or IgG occurred in all strains and the kinetics of their appearance and their levels varied according to the mouse strain, the amount and type of immune complexes were not related to susceptibility. Histological examination of brain, kidney, liver, and spleen specimens from the five mouse strains demonstrated that, while histological changes and immunopathology were apparent in the tissue from all the strains, there were marked cerebral lesions only in the susceptible strains. The investigators concluded that cerebral lesions play a significant role in the etiology of acute death in this murine malaria system which may serve as a model of human cerebral malaria. Information concerning the number of genes controlling resistance to P. berghei ANKA is not yet available. The cellular basis of the genetically determined development of cerebral pathology during this infection will be discussed in Section V.
Pathology and pathophysiology of human malaria
David A Warrell, Herbert M Gilles in Essential Malariology, 2017
Several large clinico-pathological correlations of cerebral malaria are currently underway in Thailand, Vietnam, Kenya and Malawi (Turner, 1997; Brown et al., 2001). These studies have begun to provide evidence of pathological as well as of clinical differences among these populations (see Chapters 7 and 8). Pathologically, there appears to be a higher incidence of brain swelling in African children than in South-east Asian adults, with more intravascular monocytic cell infiltrates and fibrin-platelet thrombi at the centre of haemorrhages. Some of these differences may reflect variations in treatment, time to death and host genetic responses. A number of different mechanisms may contribute to the pathophysiology of cerebral malaria, all acting through a final common pathway of neuropathological changes to cause coma and, in some cases, death.
Medical theory, medical care, and preventive medicine
Lois N. Magner, Oliver J. Kim in A History of Medicine, 2017
Misjudging the value of colchicine for gout caused Sydenham much personal discomfort, but his studies of quinine for malaria offered relief from the debilitating intermittent fever that is still worthy of the title “million-murdering death.” Symptoms of malaria include headache, fatigue, delirium, and alternating attacks of fever and chills. If we consider the impact of all diseases, as measured by the greatest harm to the greatest number, malaria has been the most devastating disease in history. Malaria has been a significant force in human evolution and in determining the success or failure of agricultural development and colonial ventures throughout the world. According to the World Health Organization, malaria attacks about 300 million people a year, and causes more than 1 million deaths, about 90% of them in Africa, but the actual number of deaths from malaria may be much higher. For hundreds of years, malaria and other murderous diseases kept Europeans from penetrating the vast African continent, but quinine became one of the tools that made European exploitation of Africa possible. In areas where malaria is highly endemic, genetic variations that enhance resistance to the disease may provide a powerful evolutionary advantage. The geographic distribution of the genes for sickle cell anemia and thalassemia seems to confirm this evolutionary strategy.
Understanding and managing the impact of the COVID-19 pandemic and lockdown on patients with epilepsy
Published in Expert Review of Neurotherapeutics, 2022
Giovanni Assenza, Lorenzo Ricci, Jacopo Lanzone, Marilisa Boscarino, Carlo Vico, Flavia Narducci, Biagio Sancetta, Vincenzo Di Lazzaro, Mario Tombini
Several clinical reports suggest an increased risk of seizure associated with chloroquine treatment [15–20]. These cases contributed to the pro-convulsant reputation of chloroquine and the consequent serious concerns about chloroquine use in PwE with SARS-COV-2 infections. However, seizures complicate the clinical course in more than 30% of children admitted to hospital with falciparum malaria[21]. They occur in over 60% of cerebral malaria cases[22] and are associated with an increased risk of death[23] and neurological sequelae[24,[25]. There are no systematic reviews that highlight a significant correlation between seizure risk and chloroquine/hydroxychloroquine therapy. However, a double-blinded randomized controlled trial on barbiturates seizure prophylaxis by Crawley and colleagues[26] showed that the occurrence of seizures in children with cerebral malaria was not correlated to the plasma level of chloroquine and its metabolites. These data support a simple indirect association between chloroquine and seizures, possibly caused by direct cerebral involvement by Plasmodium falciparum.
Optimization of artemether-loaded NLC for intranasal delivery using central composite design
Published in Drug Delivery, 2015
Kunal Jain, Sumeet Sood, Kuppusamy Gowthamarajan
Cerebral malaria (CM) is the most severe and rapidly fatal neurological complication of Plasmodium falciparum infection and responsible for more than 2 million deaths annually in nonimmune individual. This represents an enormous burden of disease, due to the high prevalence of infection (Jain et al., 2013a). It is characterized by impaired consciousness, seizures, hallucinations, severe metabolic acidosis, jaundice, renal failure and respiratory distress (Beales et al., 2000; Maitland & Newton, 2005). The underlying factors that are hallmark of cerebral malaria are sequestration and cytoadherence of infected RBC, platelets, leukocytes; rosetting, auto-agglutination, release of inflammatory cytokines, hypoxia and cerebral oedema. As a result of these central nervous system (CNS) complications, the disease may progress to unarousable coma and death (Newton et al., 2000).
Platelet interactions with viruses and parasites
Published in Platelets, 2015
Malaria is a mosquito-borne parasite infection (Plasmodium), which is transmitted to humans through the Anopheles mosquito. Malaria is a major cause of morbidity and mortality in the developing world with 207 million cases of malaria in 2012 and an estimated 627 000 deaths, mostly children under five and pregnant women who live in Sub-Saharan Africa (WHO 2013). Malaria is caused by infection with Plasmodium falciparum, P. vivax, P. ovale, P. malariae or P. knowlesi. Most of the deaths are due to infection by P. falciparum as it is the most severe infection as well as the dominant infection. Plasmodium bergei and P. chabaudi infect mice and are frequently used for animal studies. Most cases of malaria present as uncomplicated malaria with characteristic symptoms of fever, nausea and aches, however, some can present with severe malaria that involves impaired function of various organs. The most serious form of severe malaria is cerebral malaria, which is estimated to occur in 10% of hospitalized cases and is associated with 80% of deaths. Cerebral malaria occurs when infected red blood cells (RBCs) occlude cerebral blood vessels [76].