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A Pharmacological Appraisal of Antimalarial Plant Species
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Mahwahwatse J. Bapela, Precious B. Ramontja, Mcebisi J. Mabuza
The asexual stage is responsible for the pathogenesis of the disease. Intermittent fever results from the ingestion of host cytoplasm, proteolysis of hemoglobin, lysis of infected erythrocytes and a suite of host reactions. Plasmodium falciparum often exhibits continuous fever, higher levels of parasitemia and sequestration of infected erythrocytes in tissues, which explain its increased virulence, compared to the other Plasmodium species (Abdi et al., 2016; Bachmann et al., 2019). Sexual stage parasites are non-pathogenic but transmissible to the Anopheles vector. Ingestion of the gametocytes by the mosquito vector induces gametogenesis in the mid-gut of the mosquito. Microgametes fertilize macrogametes and form zygotes, which develop into ookinetes that penetrate the intestinal walls of the mid-gut and develop into oocysts. Asexual replication occurs within the oocyst and produces sporozoites. The sporozoites migrate to invade the salivary glands of the mosquitoes, thereby completing the life cycle (Yeoh et al., 2017).
Malaria Vaccines: Prospects and Problems
Published in Max J. Miller, E. J. Love, Parasitic Diseases: Treatment and Control, 2020
Three potential vaccines are being developed: A sporozoite vaccine, the aim of which is to prevent infection becoming established in the human host — a causal prophylactic effect,An asexual blood stage vaccine aimed at reducing morbidity and mortality due to malaria — a clinically attenuating vaccine,A transmission-blocking vaccine, the aim of which would be to block the development of sexual-stage parasites in the mosquito, thereby preventing the formation of sporozoites. This vaccine would protect at the community, rather than at the individual, level by reducing the level of malaria transmission in endemic areas.
Host Defense II: Acquired Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
This stage of the Plasmodium life cycle is very brief in humans, and often does not elicit specific immunity. Injection of attenuated sporozoites from irradiated carrier mosquitos has been used to induce protective immunity in humans. Antibodies induced in this way react principally with the circumsporozoite protein (CSP). CSP is important for the mobility of sporozoites, a property required for infectivity. Anti-CSP antibodies inhibit parasite mobility and increase phagocytosis. Sporozoites invade hepatocytes via specific CSP binding to a receptor (not yet known). Resistance to malaria is best predicted by high titers of anti-CSP antibodies which are neutralizing in in vitro systems. Although anti-CSP antibodies may be neutralizing and prevent hepatocyte infection, only 40% of CSP vaccine recipients in endemic regions develop protective immunity. Studies in animals showed a great dependence on MHC haplotype for response to vaccines (Ir gene control, see Chapter 8). This mechanism probably underlies the variability of human responses to CSP. Furthermore, anti-CSP antibodies, even if produced during natural infection, frequently are not neutralizing. Antibodies binding other surface molecules (such as sporozoite surface protein 2, thrombospondin related anonymous protein, liver stage specific antigens 1 and 2, and extraerythrocytic antigens) may also be protective.
Genetic disruption of nucleoside transporter 4 reveals its critical roles in malaria parasite sporozoite functions
Published in Pathogens and Global Health, 2023
Gozde Deveci, Mohd Kamil, Umit Kina, Binnur Aydogan Temel, Ahmed S. I. Aly
Mosquito cages were blood-fed with highly exflagellated Pbnt4(-) and PbWT infected mice. On days 10, 15, 18, and 21 after feeding, at least 20 mosquitoes of each genotype were dissected to get midguts for determining the number of oocysts and oocyst sporozoites per midgut as described previously [9]. On days 15, 18, and 21 post-infection, oocyst sporozoites, and salivary gland sporozoites were extracted in sterile incomplete RPMI medium containing 3% BSA (Bovine Serum Albumin) for Pbnt4(-) and PbWT infected mosquitoes. The dissected midguts and salivary glands were crushed with a pestle and centrifuged at 3000 rpm for 2 min. This step was repeated twice to ensure the proper release of all sporozoites. The number of sporozoites was counted using a hemocytometer. On days 18 and 21 post infection, hemolymph was collected from mosquitoes in isterile incomplete RPMI medium containing 3% BSA to determine the number of hemolymph sporozoites.
Multi-functional antibody profiling for malaria vaccine development and evaluation
Published in Expert Review of Vaccines, 2021
D. Herbert Opi, Liriye Kurtovic, Jo-Anne Chan, Jessica L. Horton, Gaoqian Feng, James G. Beeson
The direct inhibitory or neutralizing activity of antibodies against Plasmodium spp is evident across all parasite life cycle stages. Upon the bite of an infectious mosquito during a blood meal, sporozoites are released into the skin of the human host. From here they exit by gliding motility to invade blood vessels, actively traverse liver cells and finally invade hepatocytes where they develop and differentiate into merozoites over several days. Animal models and in vitro studies show human antibodies to sporozoites, or CSP specifically, can inhibit sporozoite motility in the dermis and the invasion of both blood vessels and hepatocytes [56-58]. Currently, widely used functional assays test the ability of antibodies to inhibit sporozoite motility and invasion [59]. However, a correlation between these measured antibody functions with protection or vaccine efficacy remains to be shown and very high antibody titers are needed for inhibitory activity; it was not found to correlate with efficacy induced by whole attenuated sporozoites [5,60].
Recent advances in quantitative structure–activity relationship models of antimalarial drugs
Published in Expert Opinion on Drug Discovery, 2021
Probir Kumar Ojha, Vinay Kumar, Joyita Roy, Kunal Roy
The life cycle of the parasites [3] completes in two stages such as asexual stage (liver and erythrocyte stages in human host) and sexual stage (inside the mosquito) [3]. The host infection starts with the bite of female Anopheles mosquito (taking the blood meal from infected human) and sporozoites injected into the human skin capillaries. This sporozoites make their way to the cells of the liver within 30 min of injecting and starts replicating asexually [3]. The schizonts rupture to give haploids form (merozoites) within 6 to 15 days in the blood stream [3]. The invasion of the merozoites gives rise to the erythrocytic stage [3,4]. In this stage, they multiply further mitotically and pass through ring forms then the feeding stage, i.e., trophozoites, then to the reproductive stage (schizonts) over the next 48 hours which gives birth of 16 new daughter merozoites for each schizont [3,4]. After maturation, the schizonts burst giving new merozoites to the blood stream [3]. The released merozoites further inject new erythrocytes to start new fever cycle that causes the clinical symptom of malaria [3]. After few cycles, the merozoites tend to develop male and female gametocytes, i.e., sexual forms (diploid zygotes) instead of new merozoites circulating into the blood stream [3,4]. They form oocyst and travel to the midgut wall of the mosquito and within 8 to 15 days sporozoites develop and migrate to the salivary glands of the mosquitoes [3]. The host infection begins when the mosquito takes blood meal and further injects sporozoites into the human blood stream [3].